tag:blogger.com,1999:blog-24246076379929828872024-03-12T18:03:36.111-04:00HCV Research and NewsHepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.comBlogger5473125tag:blogger.com,1999:blog-2424607637992982887.post-89129336917127414502017-12-08T20:54:00.001-05:002017-12-08T20:54:17.887-05:00The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: An ERCHIVES study<p><strong><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh0NYqCfHSQ_CJfXDmalZA92wAaSvSZXy6IVZgamvNN-8lqMc0GBQDi4X-R8LzYjKLj_aA5pYVlYxsjJU5uB2LQblO5PZNLprrLRdU8jwfnx0SOghcoWPHCMgO8Ms2WQeWtk2QY7ZT7hQ/s1600-h/Hepatology%255B30%255D"><img title="Hepatology" style="display: inline; background-image: none;" border="0" alt="Hepatology" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg83KWDpNng6K6B2H-5yROh6KNneGJ2irMlrZ8-FJk6B4VZeNlJG-f5XDFfqfKNXAwraXGA3yFvW5hoDxeutXaHSSb4f1EuJsmGXaWiuvnCc4RnWFWRRSl9GEZcrJJEnm4UAIjVzIig7g/?imgmax=800" width="130" height="168" /></a></strong></p> <p><strong>Hepatobiliary Malignancies</strong></p> <p>Darrick K. Li MD, PhD<sup>1,6</sup>, Yanjie Ren MS<sup>2</sup>, Daniel S. Fierer MD<sup>3</sup>, Stephanie Rutledge MD<sup>1</sup>, Obaid S. Shaikh MD<sup>2</sup>, Vincent Lo Re III MD, MSCE<sup>4</sup>, Tracey Simon MD<sup>1,6</sup>, Abdul-Badi Abou-Samra MD, PhD<sup>5,7</sup>, Raymond T. Chung MD<sup>1,6,*</sup> and Adeel A. Butt MD, MS<sup>2,5,7,*</sup></p> <p>DOI: 10.1002/hep.29707</p> <p>© 2017 by the American Association for the Study of Liver Diseases.</p> <h4>Hepatology</h4> <p><a href="http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350/accepted">Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)</a></p> <p>Publication History</p> <ol> <li>Accepted manuscript online: 2 DEC 2017 11:21AM EST </li> <li>Manuscript Accepted: 20 NOV 2017 </li> <li>Manuscript Revised: 12 NOV 2017 </li> <li>Manuscript Received: 6 JUL 2017</li> </ol> <p>Keywords: Cirrhosis; sustained virologic response; interferon; sofosbuvir; Veterans</p> <h5><font size="3">Abstract</font></h5> <p>Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct-acting antivirals (DAAs). However, making definitive conclusions has been challenging due to the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon-based regimens. We performed a retrospective population-based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. In a cohort of 17,836 persons, SVR was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. Among all treated persons, the risk of HCC was not higher in the DAA group compared to the IFN group (HR 1.07; [95% CI: 0.55, 2.08]). Among persons with cirrhosis who achieved SVR, neither the HCC incidence rate nor HCC-free survival were significantly different in the DAA group compared to the IFN group (21.2 vs. 22.8 per 1000 person years; p=0.78; and log-rank p=0.17, respectively). Untreated persons with cirrhosis had a significantly higher HCC incidence rate (45.3 per 1000 person years) compared to those treated with either IFN or DAAs (p=0.03). Both groups of treated persons had significantly lower probability of HCC development compared to untreated persons (log-rank p=0.0004).</p> <p><strong>Conclusions</strong>: DAA treatment is not associated with a higher risk of HCC in cirrhotics with chronic HCV infection in the short-term. Previously reported higher rates of HCC associated with DAA treatment may be explained by both the presence of relatively fewer baseline HCC risk factors in persons treated with IFN as well as selection bias, as DAA regimens were used to treat persons at higher risk for developing HCC. This article is protected by copyright. All rights reserved.</p> <p><a href="http://onlinelibrary.wiley.com/wol1/doi/10.1002/hep.29707/abstract" target="_blank">Source</a></p>Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-51291394064471132552017-12-08T17:51:00.001-05:002017-12-08T19:15:43.457-05:00Nonsurgical options for localized hepatocellular carcinoma<p><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh0ocsaJ1sypPhEMflEvxW_u0MP1oRGAEF9eaPQ4FHGM5BHO-eBiTgGfqA3BSlp4lxmTIYygGK0qe06hM24U9Co9oCHobsVRATrXl4IeknrHBi4oyjwy46qUlQlWEgeiGQJIiBCRAag2Q/s1600-h/cover%255B60%255D"><img title="cover" style="display: inline; background-image: none;" border="0" alt="cover" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjBT5d8vs94Jwc9qDo7sTVAUjeUMsfePGSpjtG3LVG3wfLCHoIC5RTbUXImLkPdDynhSi0Xy2zjF6dHJ7akle1eIdY7SQdK1ZV2KQVUJ8DRjqMiiuNFc6WnZwOfPSbpIfEZANgypVsqbg/?imgmax=800" width="126" height="163" /></a></p> <p><a href="http://aasldpubs.onlinelibrary.wiley.com/hub/issue/10.1002/cld.v10.4">View  issue TOC </a> <br />Volume 10, Issue 4 <br />October 2017 <br />Pages 103–106 </p> <p><strong>Review</strong></p> <p><a href="johnha1@gmail.com">John Ha M.D.</a>, Robert J. Wong M.D., M.S.</p> <p>First published: 31 October 2017</p> <p>First published: 31 October 2017 <a href="http://onlinelibrary.wiley.com/doi/10.1002/cld.662/abstract#publication-history">Full publication history</a></p> <p>DOI: 10.1002/cld.662 <a href="http://onlinelibrary.wiley.com/enhanced/exportCitation/doi/10.1002/cld.662">View/save citation</a></p> <p>Potential conflict of interest: Nothing to report.</p> <h4><font size="3">Abstract</font></h4> <p><a href="http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/10-4-reading-ha.html">Watch</a> a video presentation of this article</p> <p>Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the United States. With its current trend, HCC is projected to become the third leading cause of cancer-related deaths in the United States by 2030.[<a href="http://onlinelibrary.wiley.com/doi/10.1002/cld.662/full#cld662-bib-0001">1</a>] Currently, more than 55% of HCC cases are diagnosed beyond localized disease, and the majority do not receive definitive curative therapies, such as surgical resection or liver transplantation.[<a href="http://onlinelibrary.wiley.com/doi/10.1002/cld.662/full#cld662-bib-0001">1, 2</a>] Curative therapies are mainly reserved for patients with localized disease or those within Milan criteria. However, many nonsurgical treatment options are still available to patients with unresectable, advanced stage HCC (Table <a href="http://onlinelibrary.wiley.com/doi/10.1002/cld.662/full#cld662-tbl-0001">1</a>). Although there are many options for locoregional or systemic therapies in the management of unresectable HCC, this review will focus specifically on transarterial radioembolization (TARE), radiofrequency (RFA)/microwave ablation (MWA), stereotactic body radiation therapy (SBRT), systemic therapy, and hospice/supportive medicine. It is important to note that the approach for HCC treatment is variable and dependent on many factors, such as medical expertise, performance status, tumor stage and location, and degree of liver dysfunction. Therefore, utilizing multidisciplinary teams may provide the best option for developing a treatment plan.</p> <p><strong>Table 1.</strong> Curative Versus Noncurative Therapies for HCC</p> <p><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg0UdTHCF1U2BNiO3SgwBGhMJWA-y7VxlS2VmHhyphenhyphenOSQzjT-tNgx9-jXHnqfR0uPSUPvyEOFYQSX_5Vniu4bLMA793jHkVn2VGN8hyphenhyphenZDYnmrFq2VutbAvO-dle7bolHj8G7kvFDjDypraQ/s1600-h/Capture%255B193%255D"><img title="Capture" style="display: inline; background-image: none;" border="0" alt="Capture" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiVU8jI2TNNMpEs6hV8cEcJmkjqiOC2WRy13dcUkrGxGqOX6cRQ3Vc5AiXTNjrH5MMJN6VVTToodqYlEYi0yuN4e8uLaauvcpuRuPpkOXM7UFfYxHn-aN73atLj028Lq-neiDMTnKcBEg/?imgmax=800" width="429" height="269" /></a></p> <p>Continue reading full article <a href="http://onlinelibrary.wiley.com/doi/10.1002/cld.662/full" target="_blank">here</a></p>Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-47493986405823402992017-12-08T15:54:00.001-05:002017-12-08T17:37:02.800-05:00Where I Have Been, and I Am back.<p><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgsqyHK5467FTpVjodFrFwdUy06k3kGd2uDj_A5oHTfv5GzZiXJHmZ8xsm3awUPxSjJy5HBrtYyMnAmV-d9rUcHqjnl2_qNhZAZq0sr3fR28q6QnPTn6HZ1QmDaiZQuKznlp4S3JXXccA/s1600-h/IMG_0518%255B6%255D"><img title="IMG_0518" style="border: 0px currentcolor; border-image: none; margin-right: auto; margin-left: auto; float: none; display: block; background-image: none;" border="0" alt="IMG_0518" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjXjuhWILyj8s5o4UvNe8C_QydzMO9-eE1-_1w3NsXGlehny98Q975pMhjg_ZIbBCxNynBJEs8a6VhVxYZXcPC08_nBjqYK-m_UBVzs2mhIFCR21xPt87KtfdmrQZ2kWxe-GTc8f_QxRA/?imgmax=800" width="182" height="242" /></a></p> <p align="left"></p> <p>Everyone,</p> <p>It has been a few years since I have been here to the blog. I went back to school to work on a second BS degree and finally get my MS degree. It did not all work out according to plan though, My health decided to interfere last year so I took some off from school. May 2016 I had my 11 year post  PCR and still SVR. I also had a liver MRI done which showed 3 separate subcentimeter lesions. Let’s move ahead now to December 1st of this year, last Friday, 8 days ago …. I had a follow up MRI which showed early HCC. I have a 1.3cm mass and also a .9mm indeterminate mass. I am in the process of being referred to UNC Chapel Hill. My MRI results and other records are being reviewed there now and I am just waiting to find out who I will be seeing there and for my first appointment to be scheduled. </p> <p>My plan is to start back posting research on the blog again. It is what I feel I need to get back to doing. All the research I have done over the years has helped me to become the best advocate I can be for myself and to help others.</p> <p>Well, time to start researching and posting. It is good to be back.</p> <p>Patricia Emory</p>Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-13862155973828188142015-04-25T10:45:00.001-04:002015-04-25T10:45:20.191-04:00AbbVie Presents Late-Breaking, Preliminary Phase 3b Data with VIEKIRAX® + EXVIERA® in Chronic Hepatitis C Patients with Renal Impairment at The International Liver Congress™ 2015<p><a href="http://lh3.googleusercontent.com/-Cz-WyamwA1Y/VTuofUssTtI/AAAAAAAANTU/j7XJnainngk/s1600-h/logo_abbvie%25255B102%25255D.png"><img title="logo_abbvie" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="logo_abbvie" src="http://lh3.googleusercontent.com/-BqiwzGMD5Jo/VTuofxMBHYI/AAAAAAAANTY/HT4Wop892sk/logo_abbvie_thumb%25255B100%25255D.png?imgmax=800" width="268" height="62" /></a></p> <p>- RUBY-I evaluates treatment-naïve, non-cirrhotic, genotype 1 chronic hepatitis C patients with severe renal impairment <br />- In preliminary data from RUBY-I, patients receiving VIEKIRAX + EXVIERA with or without ribavirin who reached post-treatment week four (n=10 of 20 enrolled) achieved 100 percent sustained virologic response at four weeks post-treatment (SVR4)1 <br />- AbbVie's Phase 3b studies explore VIEKIRAX + EXVIERA in additional patient populations seen in clinical practice and across multiple countries around the world</p> <p>VIENNA, April 25, 2015 /PRNewswire/ -- AbbVie (NYSE: <a href="http://studio-5.financialcontent.com/prnews?Page=Quote&Ticker=ABBV">ABBV</a>) today announced new, preliminary safety and efficacy data from the first cohort of its ongoing, Phase 3b RUBY-I study. RUBY-I is evaluating VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA® (dasabuvir tablets) with or without ribavirin (RBV) in treatment-naïve, non-cirrhotic, genotype 1 (GT1) chronic hepatitis C patients with severe renal impairment (stage 4 or 5), including those on hemodialysis. The primary endpoint of the study is the percentage of patients achieving sustained virologic response at 12 weeks post-treatment (SVR<sub>12</sub>). Patients who reached post-treatment week four to date (n=10 of 20 enrolled) achieved 100 percent SVR<sub>4 </sub>(n=10/10).<sup>1</sup> RUBY-I was presented as a late-breaker today at The International Liver Congress™ (ILC) 2015, the 50<sup>th</sup> annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria.</p> <p>"Treating hepatitis C patients with severe renal impairment may be a concern, particularly in those patients on hemodialysis," said Paul J. Pockros, M.D., director of Liver Disease Center Scripps Clinic and director of clinical research at Scripps Translational Science Institute in La Jolla, California. "With limited data currently available on the safety and efficacy of interferon-free treatments for patients with renal impairment, the preliminary results seen in RUBY-I show promising initial SVR rates with the VIEKIRAX + EXVIERA regimen in a dedicated study for this often difficult-to-treat patient population." </p> <p>Additionally, RUBY-I data showed no virologic failures to date.<sup>1</sup> Preliminary safety analyses reported that patients experienced mainly mild or moderate adverse events when receiving VIEKIRAX + EXVIERA with or without RBV, most commonly (>20 percent) anemia, fatigue, diarrhea, nausea, dizziness and headache.<sup>1</sup> To date, eight of 13 genotype 1a (GT1a) patients had a RBV dose interruption.<sup>1</sup></p> <p>"RUBY-I is part of AbbVie's broader Phase 3b program and demonstrates our continued focus on people living with hepatitis C that have specific needs," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Studies in our Phase 3b program will help to further expand our knowledge of the utility of VIEKIRAX + EXVIERA in special populations encountered in clinical practice."</p> <p>Additional Phase 3b studies from AbbVie presented at ILC 2015 included MALACHITE-I and MALACHITE-II data, and the TOPAZ-I and TOPAZ-II study design. The MALACHITE studies evaluate adult patients with GT1 chronic HCV infection without cirrhosis receiving VIEKIRAX + EXVIERA with or without RBV compared to treatment with telaprevir with pegylated-interferon and RBV, which remains the standard of care in many regions of the world.<sup>2,3 </sup>The TOPAZ studies will evaluate the effect of SVR<sub>12</sub> on long-term outcomes, five years following treatment with VIEKIRAX + EXVIERA with or without RBV in adults with GT1 chronic HCV infection.<sup>4</sup></p> <p><b>About RUBY-I Study</b> <br />RUBY-I is an ongoing, multi-center, open-label Phase 3b study with two cohorts that evaluates the safety and efficacy of 12 or 24 weeks of treatment with VIEKIRAX® + EXVIERA® with or without ribavirin, based on sub-genotype in treatment-naïve, adult patients with genotype 1 (GT1) chronic hepatitis C virus infection who have severe renal impairment (pre-dialysis; stage 4 chronic kidney disease) or end-stage renal disease (on hemodialysis; stage 5 chronic kidney disease) with or without compensated cirrhosis.<sup>1</sup> Cohort 1 consists of 20 patients without cirrhosis and cohort 2 will evaluate approximately 20 patients with or without compensated cirrhosis. Ribavirin was started at 200mg once daily for all genotype 1a (GT1a)- infected patients and dosed four hours prior to the start of GT1a patients on hemodialysis. Additional study results, including cohort 2, will be disclosed at future scientific congresses. </p> <p><b>About VIEKIRAX® + EXVIERA® </b> <br />VIEKIRAX + EXVIERA is approved in the European Union for the treatment of genotype 1 (GT1) chronic hepatitis C virus (HCV) infection, including patients with compensated cirrhosis. VIEKIRAX is approved in the European Union for the treatment of genotype 4 (GT4) chronic HCV infection.</p> <p>VIEKIRAX consists of the fixed-dose combination of paritaprevir 150mg (NS3/4A protease inhibitor) and ritonavir 100mg with ombitasvir 25mg (NS5A inhibitor), dosed once daily, and EXVIERA consists of dasabuvir 250mg (non-nucleoside NS5B polymerase inhibitor) dosed twice daily taken with or without ribavirin (RBV), dosed twice daily based on patient type. VIEKIRAX + EXVIERA is taken for 12 weeks with or without RBV, except in GT1a and GT4 patients with compensated cirrhosis, who should take it for 24 weeks with RBV.</p> <p>Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: <a href="http://studio-5.financialcontent.com/prnews?Page=Quote&Ticker=ENTA">ENTA</a>) for hepatitis C protease inhibitors and regimens that include protease inhibitors. Paritaprevir has been developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of chronic hepatitis C.</p> <p>Additional information about AbbVie's hepatitis C development program can be found on <a href="http://www.clinicaltrials.gov/">www.clinicaltrials.gov</a>. </p> <p><b>About AbbVie's HCV Clinical Development Program</b> <br />The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating interferon-free, all-oral treatments with or without ribavirin with the goal of achieving high sustained virologic response rates in as many patients as possible. AbbVie's global Phase 3b program plans to include more than 2,800 genotype 1 patients in over 200 study centers worldwide, including the U.S., Canada, Europe, Russia and Brazil. Data in patients with severe renal impairment, including patients on hemodialysis, will be presented at ILC. Additionally, AbbVie's Phase 3b HCV program includes studies in patients with decompensated and compensated cirrhosis. Data from these studies will be presented at future scientific congresses. </p> <p>Additional information about AbbVie's hepatitis C development program can be found on <a href="http://www.clinicaltrials.gov/">www.clinicaltrials.gov</a>. </p> <p><b>VIEKIRAX</b>®<b> </b><b>+ EXVIERA</b>® <b>EU Indication <br /></b>VIEKIRAX is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults. EXVIERA is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults.</p> <p><b>Important EU Safety Information <br />Contraindications</b>: <br />VIEKIRAX + EXVIERA are contraindicated in patients with severe hepatic impairment (Child-Pugh C). Patients taking ethinyl estradiol-containing medicinal products must discontinue them and switch to an alternative method of contraception prior to initiating VIEKIRAX + EXVIERA. Do not give VIEKIRAX with certain drugs that are sensitive CYP3A substrates or strong inhibitors of CYP3A. Do not give VIEKIRAX and EXVIERA with strong or moderate enzyme inducers. Do not give EXVIERA with certain drugs that are strong inhibitors of CYP2C8.</p> <p><b>Special warnings and precautions for use</b>: <br />VIEKIRAX and EXVIERA are not recommended as monotherapy and should be used in combination with other medicinal products for the treatment of hepatitis C infection.</p> <p><i>Pregnancy and concomitant use with ribavirin <br /></i>When VIEKIRAX + EXVIERA are used in combination with ribavirin, women of childbearing potential or their male partners must use an effective form of contraception during the treatment and 6 months after the treatment. Refer to the Summary of Product Characteristics for ribavirin for additional information.</p> <p><i>ALT elevations <br /></i>Transient elevations of ALT to >5x ULN without concomitant elevations of bilirubin occurred in clinical trials with VIEKIRAX + EXVIERA and were more frequent in a subgroup who were using ethinyl estradiol-containing contraceptives.</p> <p><i>Use with concomitant medicinal products <br /></i>Use caution when administering VIEKIRAX with fluticasone or other glucocorticoids that are metabolized by CYP3A4. A reduction in colchicine dosage or interruption in colchicine is recommended in patients with normal renal or hepatic function. VIEKIRAX with or without EXVIERA is expected to increase exposure of statins so certain statins need to be discontinued or dosages reduced. Low dose ritonavir, which is part of VIEKIRAX, may select for PI resistance in HIV co-infected patients without ongoing antiretroviral therapy. HIV co-infected patients without suppressive antiretroviral therapy should not be treated with VIEKIRAX.</p> <p><b>Adverse Reactions <br /></b>Most common (>20 percent) adverse reactions for VIEKIRAX + EXVIERA with RBV were fatigue and nausea.</p> <p>Full summary of product characteristics is available at <a href="http://www.ema.europa.eu/">www.ema.europa.eu</a></p> <p><b>Globally, prescribing information varies; refer to the individual country product label for complete</b> <b>information.</b></p> <p><b>About AbbVie</b> <br />AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. AbbVie employs more than 26,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit <a href="http://www.abbvie.com/">www.abbvie.com</a>. Follow <a href="http://twitter.com/abbvie">@abbvie</a> on Twitter or view careers on our <a href="http://www.facebook.com/abbviecareers">Facebook</a> or <a href="http://www.linkedin.com/company/abbvie">LinkedIn</a> page.</p> <p><b>Forward-Looking Statements</b> <br />Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. </p> <p>Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.</p> <p><b>References:</b> <br /><sup>1</sup> Pockros P, et al. Safety Of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir For Treating HCV GT1 Infection In Patients With Severe Renal Impairment Or End-stage Renal Disease: The RUBY-I Study. Presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria  <br /><sup>2</sup> Conway B, et al. MALACHITE-I: Phase 3b Trial Of Ombitasvir/Paritaprevir/R And Dasabuvir +/-Ribavirin Or Telaprevir + Peginterferon/Ribavirin In Treatment-naïve Adults With HCV Genotype 1. Abstract presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria <br /><sup>3</sup> Dore G, et al. MALACHITE-II: Phase 3b Trial Of Ombitasvir/Paritaprevir/R And Dasabuvir + Ribavirin Or Telaprevir + Peginterferon/Ribavirin In Peginterferon/Ribavirin Treatment-experienced Adults With HCV Genotype 1. Abstract presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria  <br /><sup>4</sup> Dumas E, et al. Phase 3b Studies To Assess Long-term Clinical Outcomes In HCV GT1-infected Patients Treated With Ombitasvir/Paritaprevir/Ritonavir And Dasabuvir With Or Without Ribavirin. Abstract presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria.</p> <p>SOURCE AbbVie</p> <p>RELATED LINKS <br /><a href="http://www.abbvie.com">http://www.abbvie.com</a></p> <p><a href="http://abbvie.mediaroom.com/2015-04-25-AbbVie-Presents-Late-Breaking-Preliminary-Phase-3b-Data-with-VIEKIRAX-EXVIERA-in-Chronic-Hepatitis-C-Patients-with-Renal-Impairment-at-The-International-Liver-Congress-2015" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-68263459851679565142015-04-25T10:38:00.001-04:002015-04-25T10:38:15.373-04:00Merck Announces Presentation of Phase 2 Clinical Trial Results of Investigational Chronic Hepatitis C Therapy Grazoprevir/Elbasvir at the International Liver Congress™ 2015<p><em>Results of C-SALVAGE Study Showed High Sustained Virologic Response Rates in Patients Who Failed Prior Combination Therapy with Certain Direct Acting Antiviral (DAA) Agents</em></p> <p><em>Results of C-SWIFT Study Provide Proof-of-Concept for Shorter Than Twelve Weeks Duration of Treatment with Triple-DAA Regimen in Patients with Chronic Hepatitis C Virus (HCV) Genotypes 1 and 3 Infection</em></p> <p>Saturday, April 25, 2015 9:00 am EDT </p> <p>VIENNA – April 25, 2015<b> </b>– Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of results from two Phase 2 clinical trials evaluating the safety and efficacy of the company’s investigational once-daily treatment regimen of grazoprevir (100mg) and elbasvir (50mg)<a href="file:///C:/Users/clinebel/AppData/Local/Microsoft/Windows/Temporary%20Internet%20Files/Content.Outlook/M6WLBSGE/EASL%202015%20Trade%20Roundup%20Data%20Release%20FINAL%20MERCKCOM.docx">[1]</a> in adult patients with chronic hepatitis C virus (HCV) infection. Treatment with grazoprevir and elbasvir in combination with ribavirin (RBV) (<i>C-SALVAGE </i>trial) showed high rates of sustained virologic response 12 weeks after the completion of treatment (SVR12) in patients with chronic HCV genotype 1 (GT1) infection with or without liver cirrhosis who previously failed combination therapy with a DAA agent. In addition, final results from the <i>C-SWIFT</i> study evaluating grazoprevir/elbasvir in combination with sofosbuvir 400mg in treatment-naïve patients with or without liver cirrhosis chronically infected with HCV GT1 or GT3 were presented as proof-of-concept for potentially shortening HCV treatment duration below 12 weeks. Data from these studies were presented at <a href="https://ilc-congress.eu/">The International Liver Congress<sup>TM </sup>2015</a> – the 50<sup>th</sup> annual congress of the European Association for the Study of the Liver.</p> <p>“We continue to advance our Phase 3 clinical program for grazoprevir/elbasvir evaluating diverse patient populations with chronic HCV infection, including those widely considered among the most difficult to treat,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “Findings from these Phase 2 studies formed part of the basis for our decision to rapidly advance our large and comprehensive clinical development program that incorporates studies dedicated to patient populations with specific unmet medical needs.”</p> <p><b><i>C-SALVAGE Overview and Findings</i></b></p> <p><a href="https://clinicaltrials.gov/ct2/show/NCT02105454"><i>C-SALVAGE</i></a> (Abstract #O001) is a<i> </i>Phase 2, single arm, open label<i> </i>clinical trial<i> </i>conducted to<i> </i>evaluate the efficacy and safety of 12 weeks of treatment with grazoprevir and elbasvir plus RBV in patients with chronic HCV GT1 infection who have previously failed treatment with peginterferon and RBV combined with a DAA (boceprevir, simeprevir or telaprevir). Of the 79 patients who received one or more doses of grazoprevir and elbasvir, 43 percent had liver cirrhosis.  </p> <p>Following 12 weeks of treatment with a combination of grazoprevir and elbasvir plus RBV, 96 percent of the patients (76/79) with chronic HCV GT1 infection who had failed prior treatment with specified DAA-based regimens achieved SVR12. Ninety four percent (32/34) of patients with compensated cirrhosis achieved SVR12. Virologic failure was reported for three patients in the trial. All three patients had resistance associated variants at baseline and relapsed after completion of study treatment.</p> <p>The most common adverse events included fatigue (28%), headache (19%), asthenia (15%) and nausea (12%). Five serious adverse events were reported, none of which were considered related to study drug. One patient discontinued treatment due to an adverse event that was not considered to be drug-related. Detailed findings of the study were recently posted online in the “Articles in Press” section of the <a href="http://www.journal-of-hepatology.eu/article/S0168-8278(15)00291-3/abstract"><i>Journal of Hepatology</i></a>, the official journal of the European Association for the Study of the Liver.</p> <p><b><i>C-SWIFT Overview and Findings</i></b></p> <p><a href="https://clinicaltrials.gov/ct2/show/NCT02133131"><i>C-SWIFT</i></a> (Abstract #O006) is a proof-of-concept Phase 2 open label clinical trial conducted to evaluate the efficacy and safety of grazoprevir/elbasvir plus sofosbuvir over shorter treatment durations. Specifically, treatment-naïve patients with or without liver cirrhosis chronically infected with HCV GT1 were treated for 4, 6 or 8 weeks and treatment-naïve patients with or without liver cirrhosis chronically infected with HCV GT3 were treated for 8 or 12 weeks. Interim findings were previously presented at the 65<sup>th</sup> American Association for the Study of Liver Diseases in November 2014.</p> <p><a href="http://lh3.googleusercontent.com/-VjzJeX-UgZQ/VTum1Irc9aI/AAAAAAAANTA/_n3eSGfQCes/s1600-h/Capture%25255B4%25255D.png"><img title="Capture" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="Capture" src="http://lh3.googleusercontent.com/-SW23knS-Sc8/VTum1UZEzHI/AAAAAAAANTI/BjeA0l3bDjQ/Capture_thumb%25255B2%25255D.png?imgmax=800" width="442" height="306" /></a></p> <p>SVR12 results by treatment arm in the modified intent to treat population are shown above (table 1).  Among GT1 patients, virologic relapse occurred in 20 non-cirrhotic patients receiving four weeks of treatment, in four non-cirrhotic and four cirrhotic patients receiving six weeks of treatment, and in one cirrhotic patient receiving eight weeks of treatment. Among GT3 patients, virologic relapse occurred in one non-cirrhotic patient receiving eight weeks of treatment, and in one cirrhotic patient receiving 12 weeks of treatment. There were no reported cases of virologic breakthrough.</p> <p>No patients discontinued due to treatment-related adverse events. The most common adverse events reported across all treatment groups and genotypes were headache (4% overall, range 2-8% across treatment arms), fatigue (2% overall, range 0-8% across treatment arms) and nausea (2% overall, range 2-8% across treatment arms). Two serious adverse events – pyelonephritis and B-cell lymphoma – were reported but were not considered to be related to study medicine.</p> <p><b>About Grazoprevir/Elbasvir</b></p> <p>Grazoprevir/elbasvir is an investigational, once-daily single tablet regimen consisting of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A replication complex inhibitor). As part of Merck’s broad clinical trials program, grazoprevir/elbasvir is being studied in multiple HCV genotypes and in patients with difficult-to-treat conditions such as HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, liver cirrhosis and those on opiate substitution therapy.</p> <p><b>Merck’s Commitment to HCV</b></p> <p>For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative health care solutions that support people living with HCV worldwide.</p> <p><b>About Merck</b></p> <p>Today’s Merck is a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. For more information, visit <a href="http://www.merck.com/">www.merck.com</a> and connect with us on <a href="https://twitter.com/Merck">Twitter</a>, <a href="http://www.facebook.com/MerckBeWell">Facebook</a> and <a href="http://www.youtube.com/Merck">YouTube</a>.</p> <p><b>Forward-Looking Statement</b></p> <p>This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.</p> <p>Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.</p> <p>Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise except as required by applicable law. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2014 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (<a href="http://www.sec.gov/">www.sec.gov</a>).</p> <p><a href="file:///C:/Users/clinebel/AppData/Local/Microsoft/Windows/Temporary%20Internet%20Files/Content.Outlook/M6WLBSGE/EASL%202015%20Trade%20Roundup%20Data%20Release%20FINAL%20MERCKCOM.docx">[1]</a> Grazoprevir is a HCV NS3/4A protease inhibitor and elbasvir is a HCV NS5A replication complex inhibitor</p> <p><strong>CONTACTS:</strong></p> <p>Merck Media: Doris Li (908) 246-5701</p> <p>or</p> <p>Sarra Herzog (201) 669-6570</p> <p>Investor: Joe Romanelli (908) 740-1986</p> <p>or</p> <p>Justin Holko (908) 740-1879</p> <p><a href="http://www.mercknewsroom.com/news-release/hepatitis-c-newsroom/merck-announces-presentation-phase-2-clinical-trial-results-invest" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-56205198950165449202015-04-25T10:26:00.001-04:002015-04-25T10:26:06.260-04:00ALLY-1 Trial Results Show Investigational Daclatasvir-Based Regimen Cures 94% of Post-Liver Transplant Patients with Hepatitis C and Up to 94% of Hepatitis C Patients with Cirrhosis (Child-Pugh Class A or B)<p><a href="http://lh3.googleusercontent.com/-V9OX18MiDgw/VTuj-pmKQ4I/AAAAAAAANSs/gxZzSJLE1JQ/s1600-h/bms_logo%25255B76%25255D.gif"><img title="bms_logo" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="bms_logo" src="http://lh3.googleusercontent.com/-A5Kr2JVTkhg/VTuj_JMmDZI/AAAAAAAANS0/CoxatktqxJU/bms_logo_thumb%25255B74%25255D.gif?imgmax=800" width="315" height="67" /></a></p> <p><b><i>97% of post-transplant patients with HCV genotype 1a achieved cure</i></b></p> <p><b><i>91% of post-transplant patients with HCV genotype 3 achieved cure  </i></b></p> <p><b><i>No need seen to alter existing transplantation medication regimens </i></b></p> <p>Saturday, April 25, 2015 10:00 am EDT </p> <h4>Dateline: </h4> <p>PRINCETON, N.J., APRIL 25, 2015 </p> <p><a href="http://news.bms.com/printmail/5409">Email</a><a href="http://news.bms.com/printpdf/5409">PDF</a><a href="http://news.bms.com/print/node/5409">Print</a><a href="http://news.bms.com/feeds/press_release/all/rss.xml">RSS</a></p> <p>(PRINCETON, N.J., APRIL 25, 2015)<i> – </i><a href="http://www.bms.com/">Bristol-Myers Squibb Company</a> (NYSE:BMY) today announced that primary endpoints were successfully met in ALLY-1, a Phase III clinical trial evaluating a 12-week regimen of daclatasvir and sofosbuvir once-daily with ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) with either advanced cirrhosis or post-liver transplant recurrence of HCV. The data was presented as a late-breaker at The International Liver Congress™ 2015, the 50<sup>th</sup> annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria from April 22-26.</p> <p>“The results of the ALLY-1 trial point to the potential of this investigational daclatasvir-based regimen in a patient population with high unmet needs despite recent advances in hepatitis C treatment,” said Fred Poordad, M.D., ALLY-1 Lead Investigator and Clinical Professor of Medicine at The University of Texas Health Science Center at San Antonio. “Transplant patients take a variety of immunosuppressive medications to prevent organ rejection; that complicates the treatment of hepatitis C. In ALLY-1, we saw no drug-drug interactions between transplant and hepatitis C therapies and no need to make dose adjustments to patients’ transplant-related drugs while they received the daclatasvir-based regimen that resulted in high SVR12 rates.”</p> <p>The study’s primary endpoints were reached, with 95% of post-transplant genotype 1 patients and 82% of genotype 1 patients with advanced cirrhosis achieving SVR12. Among all ALLY-1 patients, 94% of those with post-transplant HCV recurrence and 83% of all participants with advanced cirrhosis achieved cure (sustained virologic response 12 weeks after treatment; SVR12).</p> <p>The Child-Pugh scoring system is commonly used to assess the severity and prognosis of chronic liver disease and cirrhosis, and uses an A through C classification (C being the most advanced) to categorize disease progression. Patients with class C cirrhosis are decompensated, often with later-stage conditions such as ascites (the build-up of fluid in the abdomen), hepatic encephalopathy (confusion or altered level of consciousness due to the liver’s inability to remove toxins from the blood), and abnormal liver function, which can complicate treatment. The ALLY-1 trial included 16 patients with decompensated cirrhosis Child-Pugh class C; nine (56%) achieved SVR12.</p> <p>Over the course of the study, four advanced cirrhotic patients received a liver transplant during treatment; 3 of 4 extended treatment post-transplant (see study design below), and all 4 achieved SVR12.</p> <p>In the study, there were no serious adverse events related to study medications throughout the treatment phase. The most common adverse events (≥10%) were headache (15%, 36%), fatigue (18%, 28%), anemia (20%, 19%), diarrhea (8%, 19%), nausea (17%, 6%), and arthralgia (2%, 13%) in the advanced cirrhotic and post-transplant cohorts, respectively. One patient discontinued therapy after 31 days due to headache, but still achieved SVR12. Nine patients in the cirrhosis cohort relapsed post-treatment, and one had detectable HCV RNA at the end of treatment; there were no on-treatment virologic breakthroughs. Three patients (genotypes 1a, 1b, 3) in the post-transplantation cohort relapsed. All 12 patients with relapse are being retreated with daclatasvir and sofosbuvir with ribavirin for 24 weeks. </p> <p> HCV is the leading indication for liver transplantation worldwide. Without treatment, HCV infection of the new liver after transplant is inevitable, and is associated with rapid progression to cirrhosis and death in up to 30% of patients within 5 years. The ALLY-1 study is the third study to report out of the Phase III ALLY program, which evaluates daclatasvir in combination with sofosbuvir in multiple high-unmet need patient populations and is at the center of Bristol-Myers Squibb’s HCV research focus. The ALLY-2 and ALLY-3 studies have previously been presented at the 2015 Conference for Retroviral and Opportunistic Infections and the 2014 American Association for the Study of the Liver’s The Liver Meeting, respectively, and subanalyses from each study with the ribavirin-free regimen of daclatasvir and sofosbuvir were presented as posters during EASL 2015.</p> <p>Additionally, EASL issued 2015 Hepatitis C treatment guidelines that include a regimen of daclatasvir+sofosbuvir as the first 12-week treatment for patients with genotype-3 virus. The EASL guidelines now list daclatasvir+sofosbuvir regimens as options for treating all HCV genotypes and for use with patients coinfected with HCV/HIV. (Guidelines available <a href="http://www.journal-of-hepatology.eu/article/S0168-8278(15)00208-1/fulltext">here</a>.)</p> <p>Other Bristol-Myers Squibb presentations at The International Liver Congress included data from compassionate use programs in the EU that add to the real-world clinical evidence informing the use of daclatasvir-based regimens to treat patients with HCV conditions posing high unmet medical needs. </p> <p>“The ALLY-1 trial results build off the ALLY-2 and ALLY-3 studies by demonstrating the versatility of the daclatasvir-based regimen to provide HCV cure in multiple patient populations that have been historically hard to manage, such as HCV genotype 3 patients, HIV/HCV coinfected patients, and patients with decompensated cirrhosis,” said Douglas Manion, M.D., Head of Specialty Development, Bristol-Myers Squibb. “Post-liver transplant and cirrhotic patients represent a still-unmet need and continue to present challenges to currently available regimens.”  </p> <p><b>About ALLY-1: Study Design</b></p> <p>This Phase III open-label clinical trial enrolled treatment-naïve and treatment-experienced patients with HCV infection of any genotype in 2 cohorts: advanced cirrhosis (n=60) and post-liver transplant with HCV recurrence (n=53). All patients received daclatasvir 60 mg plus sofosbuvir 400 mg once-daily with ribavirin initially dosed at 600 mg/d (with potential for adjustment based on hemoglobin levels and creatinine clearance) for 12 weeks. Patients receiving a variety of immunosuppressive agents were permitted. In the cirrhosis cohort, patients transplanted during treatment could receive 12 weeks of extended treatment immediately post-transplant, regardless of treatment duration before transplant. The primary endpoint was the SVR12 rate (defined as HCV RNA <LLOQ (25 IU/mL) at post-treatment week 12) among genotype 1 patients in each cohort.</p> <p><b>About Hepatitis C</b></p> <p>Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Approximately 170 million people worldwide are infected with hepatitis C. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20 percent of people with chronic hepatitis C will develop cirrhosis; of those, up to 20 percent may progress to liver cancer.</p> <p><b>About Bristol-Myers Squibb’s HCV Portfolio</b></p> <p>Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir, a NS5A complex inhibitor which continues to be investigated in multiple treatment regimens and in patients with co-morbidities.</p> <p>Daclatasvir<i> </i>was approved in Europe in August 2014 for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection in adults. Beyond Europe, it is approved in Japan, as well as multiple countries in Latin and South America, the Middle East and Asia Pacific. Additionally, the U.S. FDA currently is reviewing a New Drug Application (NDA) for the use of daclatasvir and sofosbuvir to treat patients with HCV genotype 3.</p> <p><b>About Bristol-Myers Squibb</b></p> <p>Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.bms.com&esheet=50778389&newsitemid=20140108005183&lan=en-US&anchor=http%3A%2F%2Fwww.bms.com&index=3&md5=7c6907d02707cca3a1b2fd49772997df">http://www.bms.com</a> or follow us on Twitter at <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Ftwitter.com%2Fbmsnews&esheet=50778389&newsitemid=20140108005183&lan=en-US&anchor=http%3A%2F%2Ftwitter.com%2Fbmsnews&index=4&md5=5a14d054bf194861658e80c18e8a084d">http://twitter.com/bmsnews</a>.</p> <p><b>Bristol-Myers Squibb Forward Looking Statement</b></p> <p><i>This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that daclatasvir will receive regulatory approval in the United States, or if approved, that it will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2014, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.</i></p> <p><b>Contact:</b></p> <p><b>Media:</b> <br />Robert Perry, Office: 609-419-5378, Cell: 407-492-4616, <a href="mailto:rob.perry@bms.com">rob.perry@bms.com</a> </p> <p><b>Investors:</b> <br />Ranya Dajani, 609-252-5330, <a href="mailto:ranya.dajani@bms.com">ranya.dajani@bms.com</a></p> <p><a href="http://news.bms.com/press-release/ally-1-trial-results-show-investigational-daclatasvir-based-regimen-cures-94-post-live" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-82445699718112623252015-04-25T01:07:00.001-04:002015-04-25T01:11:29.682-04:00Gilead Announces Results From Studies Evaluating Sofosbuvir-Based Regimens in Chronic Hepatitis C Patients With Genotypes 2-5<p><a href="http://lh3.googleusercontent.com/-X8BhjT4r6PE/VTshINbp43I/AAAAAAAANSQ/i7rQ4fO8HDU/s1600-h/Gilead%25255B26%25255D.gif"><img title="Gilead" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="Gilead" src="http://lh3.googleusercontent.com/-9gTMBhZ1AAQ/VTshJEooXXI/AAAAAAAANSY/zO1zwYXNHss/Gilead_thumb%25255B24%25255D.gif?imgmax=800" width="226" height="77" /></a></p> <p><i><b>-- High Cure Rates Observed Across a Range of Genotypes --</b></i></p> <p>VIENNA, Austria--(BUSINESS WIRE)--Apr. 25, 2015-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from two studies evaluating the safety and efficacy of investigational uses of sofosbuvir-based regimens in chronic hepatitis C virus (HCV)-infected patients with genotypes 2, 3, 4 and 5. Results from the BOSON study of Sovaldi<sup>®</sup> (sofosbuvir 400 mg) in combination with ribavirin (RBV) or with pegylated interferon (PEG)/RBV demonstrated high cure rates across all patients with genotypes 2 and 3. Separately, results from a Phase 2 study demonstrate the safety and efficacy of Harvoni<sup>®</sup> (ledipasvir 90 mg/sofosbuvir 400 mg) in patients with genotypes 4 or 5 infection. Data from both studies will be presented in oral sessions at the 50th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress™ 2015) in Vienna, Austria. </p> <p>Sovaldi and Harvoni are each approved in the United States for the treatment of chronic HCV infection. Sovaldi is used in combination with other agents and its efficacy has been established in patients with genotypes 1-4; Harvoni is indicated for patients with genotype 1. </p> <p>BOSON (Study GS-US-334-0153, #LB05), a randomized Phase 3 study of 592 patients, evaluated the safety and efficacy of Sovaldi plus RBV for 16 or 24 weeks compared with Sovaldi plus PEG/RBV for 12 weeks among treatment-naïve or treatment-experienced genotype 3 patients with and without cirrhosis and treatment-experienced genotype 2 patients with cirrhosis. Thirty-seven percent of study participants had cirrhosis. </p> <p>Among genotype 3 patients, rates of sustained virologic response 12 weeks after treatment (SVR12) were highest among those receiving Sovaldi plus PEG/RBV for 12 weeks (93 percent, n=168/181), compared to those receiving Sovaldi plus RBV for 24 weeks (84 percent, n=153/182) or for 16 weeks (71 percent, n=128/181). Treatment-experienced genotype 3 patients with cirrhosis receiving Sovaldi plus PEG/RBV demonstrated SVR12 rates of 86 percent (30/35). </p> <p>Genotype 2 patients also demonstrated high SVR12 rates across all treatment arms. SVR12 rates among patients receiving Sovaldi plus PEG/RBV were 94 percent (15/16), and 100 percent (17/17) and 87 percent (13/15) for those receiving Sovaldi plus RBV for 24 and 16 weeks, respectively. </p> <p>Sovaldi plus PEG/RBV and Sovaldi plus RBV were well tolerated. The most common adverse events in the study were fatigue, headache, insomnia and nausea. Overall, six patients (1 percent) discontinued treatment due to adverse events, one of whom was treated with Sovaldi plus PEG/RBV. </p> <p>“It remains difficult to achieve a virological response in genotype 3, which is one of the most prevalent genotypes in the world, with higher prevalence in Europe and Asia,” said Graham R. Foster, FRCP, PhD, Professor of Hepatology, The Liver Unit, Queen Mary's University of London, Barts Health, London, United Kingdom. “These results are compelling because they represent the highest cure rates observed among treatment-experienced, cirrhotic genotype 3 patients in any Phase 3 clinical trial to date.” </p> <p>In a separate open-label Phase 2 study of Harvoni conducted in France (Study GS-US-337-1119, O056), results demonstrated high SVR rates in both treatment-naïve and treatment-experienced patients with chronic HCV genotypes 4 or 5 infection, 50 percent of whom had cirrhosis. </p> <p>Ninety-three percent of patients with genotype 4 (41/44) and 95 percent of patients with genotype 5 (39/41) achieved SVR12. Response rates were similar among both treatment-naïve and -experienced patients and regardless of cirrhosis. </p> <p>The most common adverse events (affecting more than 10 percent of patients) were asthenia, headache and fatigue. Most adverse events were mild or moderate in severity and none resulted in treatment discontinuation. There were no grade 3 or 4 clinical laboratory abnormalities. </p> <p>“HCV genotype 4 and 5 are less prevalent than other genotypes and therefore, have traditionally not been closely studied,” said Armand Abergel, MD, PhD, Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire-Estaing, Université d'Auvergne, Clermont-Ferrand, France. “These data provide important evidence that the all-oral, ribavirin-free Harvoni regimen is both safe and effective for many patients with genotype 4 or 5, regardless of prior treatment experience.” </p> <p>The safety and efficacy of these investigational uses of Harvoni and Sovaldi have not been established. </p> <p><b>Important Safety Information About Sovaldi</b></p> <p><b>Contraindications</b></p> <p>Sovaldi combination treatment with ribavirin or with peginterferon alfa plus ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risk for birth defects and fetal death associated with ribavirin. Contraindications to peginterferon alfa and ribavirin also apply to Sovaldi combination treatment. Refer to the prescribing information of peginterferon alfa and ribavirin for a list of their contraindications. </p> <p><b>Warnings and Precautions</b></p> <p><b>Serious Symptomatic Bradycardia When Coadministered with Amiodarone and Another HCV Direct Acting Antiviral (DAA):</b> Amiodarone is not recommended for use with Sovaldi in combination with another DAA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia. </p> <p><b>Pregnancy:</b> Use with ribavirin or peginterferon alfa/ribavirin: Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Female patients of childbearing potential and their male partners must use two forms of non-hormonal contraception during treatment and for at least 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. Refer to the prescribing information for ribavirin. </p> <p><b>Use with Potent P-gp Inducers: </b>Rifampin and St. John’s wort should not be used with Sovaldi as they may significantly decrease sofosbuvir plasma concentration, reducing its therapeutic effect. </p> <p>Adverse Reactions </p> <p>Most common (≥20 percent, all grades) adverse reactions for: </p> <p>Sovaldi + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia, and anemia </p> <p>Sovaldi + ribavirin combination therapy were fatigue, and headache </p> <p><b>Drug Interactions</b></p> <p>In addition to rifampin and St. John’s wort, coadministration of Sovaldi is not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of sofosbuvir, reducing its therapeutic effect. </p> <p><b>Important Safety Information About Harvoni</b></p> <p><b>Warnings and Precautions</b></p> <p><b>Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:</b> Amiodarone is not recommended for use with Harvoni due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia. </p> <p><b>Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers:</b> Rifampin and St. John’s wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations. </p> <p><b>Related Products Not Recommended:</b> Harvoni is not recommended for use with other products containing sofosbuvir (Sovaldi). </p> <p><b>Adverse Reactions</b></p> <p>Most common (≥10 percent, all grades) adverse reactions were fatigue and headache. </p> <p><b>Drug Interactions</b></p> <p>In addition to rifampin and St. John’s wort, coadministration of Harvoni is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of Harvoni. </p> <p>Coadministration of Harvoni is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively. </p> <p>Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments. </p> <p><b>About Gilead</b></p> <p>Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California. </p> <p><b>Forward-Looking Statement</b></p> <p>This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that Gilead may observe unfavorable results from additional clinical trials involving Sovaldi and Harvoni for various patient populations, including those with genotype 2, 3, 4 and 5 HCV. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements. </p> <p><i>U.S. full Prescribing Information for Sovaldi and Harvoni is available at </i><a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.gilead.com&esheet=51087824&newsitemid=20150424005946&lan=en-US&anchor=www.gilead.com&index=1&md5=a7ad0653a27606c2d06f55cf5f93f46c"><i></i></a><i><a href="http://www.gilead.com/">www.gilead.com</a></i>. </p> <p><i>Sovaldi and Harvoni are registered trademarks of Gilead Sciences, Inc., or its related companies.</i></p> <p><i>For more information on Gilead Sciences, please visit the company’s website at </i><a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.gilead.com%2F&esheet=51087824&newsitemid=20150424005946&lan=en-US&anchor=www.gilead.com&index=2&md5=e65441c4587ed361d1d89ecb1f82a47c"><i></i></a><i><a href="http://www.gilead.com/">www.gilead.com</a></i><i>, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.</i></p> <p>Source: Gilead Sciences, Inc.</p> <p>Gilead Sciences, Inc. <br />Sung Lee, +1 650-524-7792 (Investors) <br />Nathan Kaiser, +1 650-522-1853 (Media) <br />Michele Rest, +1 650-577-6935 (Media)</p> <p><a href="http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=2040081" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-91032257200464041122015-04-25T00:29:00.001-04:002015-04-25T00:29:47.721-04:00Cancer rates among patients with hepatitis C are increased compared to those not infected<p><a href="http://lh3.googleusercontent.com/-V1JNpU1daps/VTsYODhFsrI/AAAAAAAANR4/JOydxbqgRv8/s1600-h/50thcongress%25255B67%25255D.png"><img title="50thcongress" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="50thcongress" src="http://lh3.googleusercontent.com/-R6Nk43nz8lA/VTsYOhZi3dI/AAAAAAAANR8/qjf9OxuTPnU/50thcongress_thumb%25255B65%25255D.png?imgmax=800" width="301" height="54" /></a></p> <p>Public Release: 24-Apr-2015</p> <p><em><strong><font size="3">Researchers suggest an extrahepatic manifestation of hepatitis C may be an increased risk of cancer</font></strong></em></p> <p><font size="3">European Association for the Study of the Liver</font></p> <p>April 24, 2015, Vienna , Austria: Results announced today at The International Liver CongressTM 2015 show that cancer rates in patients with the hepatitis C virus (HCV) were significantly increased compared to the non-HCV cohort. The researchers suggest an extrahepatic manifestation of HCV may be an increased risk of cancer.</p> <p>The aim of the study was to describe the rates of all cancers in the cohort of HCV patients compared to the non-HCV population. Known cancer types associated with hepatitis C include non-Hodgkin's lymphoma, renal and prostate cancers, as well as liver cancer.</p> <p>A retrospective study at Kaiser Permanente, Southern California, USA, was conducted. The study authors recorded all cancer diagnoses in patients over 18 years of age with or without HCV during 2008-2012. Within the timeframe of the study 145,210 patient years were included in the HCV cohort, and 13,948,826 patient years were included in the non-HCV cohort.</p> <p>In the HCV cohort there were 2,213 cancer diagnoses (1,524/100,000) during the 5-year period and 1,654 cancer diagnoses when liver cancer was excluded (1,139/100,000). In the non-HCV cohort there were 84,419 cancer diagnoses (605/100,000) during the same 5-year period and 83,795 (601/100,000) when liver cancer was excluded. When all cancers are considered the rate is 2.5 times higher in the HCV cohort; when liver cancers are excluded, the rate is still almost 2 times higher. </p> <p>Lisa Nyberg, MD, MPH, Kaiser Permanente, Southern California, senior author of the study, explains: "The results suggest that cancer rates are increased in the cohort of hepatitis C patients versus the non-hepatitis C patients, both including and excluding liver cancers. These findings certainly point to the suggestion that hepatitis C may be associated with an increased risk of cancer. However, the findings must be interpreted with caution, as the study also showed that confounding factors such as alcohol abuse, tobacco, obesity, and diabetes modified the results." </p> <p>Dr Laurent Castera, Vice-Secretary, European Association for the Study of the Liver, commented: "This data adds to the evidence bank linking hepatitis C with an increased risk of cancer, and highlights that there is still a long way to go in order to fully understand this complex and devastating disease." </p> <p>###</p> <p><b>About The International Liver Congress™ </b></p> <p>This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.</p> <p><b>About <a href="http://www.easl.eu/">EASL</a></b></p> <p>Since EASL's foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from more than 100 countries around the world. EASL is the leading liver association in Europe, it attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.</p> <p><b>Contact</b></p> <p>For more information, please contact the ILC Press Office at: </p> <p><a href="mailto:ilc.press@easloffice.eu">ilc.press@easloffice.eu</a> or <br />+44 (0)20 3580 5444 </p> <p><b>INCREASED CANCER RATES IN PATIENTS WITH CHRONIC HEPATITIS C: AN ANALYSIS OF THE CANCER REGISTRY IN A LARGE U.S. HEALTH MAINTENANCE ORGANIZATION</b></p> <p>Anders H. Nyberg* 1, Joanie W. Chung2, Jiaxiao M. Shi3, T. C. Cheetham3, Kevin M. Chiang4, Reina Haque5, Zobair M. Younossi6, Lisa M. Nyberg1 </p> <p>1Gastroenterology/Hepatology, Kaiser Permanente, San Diego, 2Kaiser Permanete, Research and Evaluation, 3Research and Evaluation, Kaiser Permanente, Pasadena, 4Pharmacy Analytical Services, Kaiser Permanente, Downey, 5Research and Evaluatuion, Kaiser Permanente, Pasadena, 6Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, United States</p> <p><b></b></p> <p><b>Background and Aims:</b> Hepatitis C virus (HCV) is an oncogenic virus, and an increased risk of malignancy in HCV has previously been reported. Cancer types associated with HCV include non-Hodgkin's lymphoma, renal and prostate cancers; as well as liver cancer. The aim of this study was to describe cancer rates in our cohort of HCV patients compared to cancer rates in the non-HCV population.</p> <p><b>Methods:</b> This is a retrospective study at Kaiser Permanente Southern California (KPSC), a large health maintenance organization with 3.5-4 million members. The KPSC cancer registry is an accredited program maintaining a complete profile of all cancer diagnoses for all KP members. In this study, we recorded all cancer diagnoses in patients ?18 years of age with or without HCV during 2008-2012.</p> <p><b>Results:</b> From 2008 to 2012, 145,210 patient years were included in the HCV cohort, and 13,948,826 patient years were included in the non HCV cohort. Mean age at cancer diagnosis in the HCV cohort was 61.8 years, in the non-HCV cohort, 63.5 years. In the HCV cohort there were 2,213 cancer diagnoses (1524/100000) during the 5 year period and 1,654 cancer diagnoses when liver cancer was excluded (1139/100000). In the non HCV cohort there were 84,419 cancer diagnoses (605/100000) during the same 5 year period and 83,795 (601/100000) when liver cancer was excluded. The rate ratios between the HCV and non HCV cohorts for the total number of cancer cases including and excluding liver cancer are shown in Table 1.</p> <p><b>Conclusions:</b> In our cohort of Hepatitis C infected patients, cancer rates were significantly increased compared to the non-HCV cohort. This suggests that another extrahepatic manifestation of HCV may be an increased risk of cancer. </p> <p><a href="http://www.eurekalert.org/pub_releases/2015-04/eaft-cra042315.php" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-13934628960517909252015-04-24T12:34:00.001-04:002015-04-24T12:34:37.485-04:00EMA recommends avoidance of certain hepatitis C medicines and amiodarone together<p>Press Release</p> <p><a href="http://lh3.googleusercontent.com/-yF44imBx72M/VTpwmo8wEeI/AAAAAAAANRc/T5aKvQmtg8Y/s1600-h/Capture%25255B98%25255D.png"><img title="Capture" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="Capture" src="http://lh3.googleusercontent.com/-mcduMr5LEgA/VTpwm1h21dI/AAAAAAAANRg/0I-oyVM3fC0/Capture_thumb%25255B96%25255D.png?imgmax=800" width="337" height="66" /></a></p> <p>24/04/2015 </p> <p><strong>Concomitant use may increase risk of slow heart rate and related problems</strong></p> <p>The European Medicines Agancy (EMA) has confirmed a risk of severe bradycardia (slow heart rate) or heart block (problems with conduction of electrical signals in the heart) when the hepatitis C medicines Harvoni (sofosbuvir with ledipasvir) or a combination of Sovaldi (sofosbuvir) and Daklinza (daclatasvir) are used in patients who are also taking the medicine amiodarone, which is an antiarrhythmic (a medicine used to treat irregular heartbeat).</p> <p>To manage this risk the Agency recommends that amiodarone should only be used in patients taking these hepatitis C medicines if other antiarrhythmics cannot be given. If concomitant use with amiodarone cannot be avoided, patients should be closely monitored. Because amiodarone persists for a long time in the body, monitoring is also needed if patients start such hepatitis C treatments within a few months of stopping amiodarone.</p> <p>The recommendations follow a review<sup>1</sup> of cases of severe bradycardia or heart block in patients taking amiodarone who started treatment with the hepatitis C combinations. It was considered that there was a likely relationship of these events to the medicines. The possible mechanism behind these effects is unknown and further investigation of other cases with Sovaldi and other hepatitis C medicines is ongoing.</p> <p><strong>Information for patients</strong></p> <ul> <li>A few cases of severe slow heart rate or interference with electrical signals in the heart have been reported in patients taking the medicines Harvoni or Sovaldi plus Daklinza (used to treat hepatitis C, a liver infection) at the same time as the heart medicine amiodarone. </li> <li>Most of these cases occurred within 24 hours of starting the hepatitis C medicine but some occurred after up to 12 days. Two of the patients needed treatment with a pacemaker and one patient died. </li> <li>Patients who need these hepatitis C combinations should not also be given amiodarone unless there is no other suitable alternative. </li> <li>If there is no alternative to giving amiodarone at the same time as the hepatitis C medicine, patients’ heart function must be carefully monitored by the doctor. This may include monitoring in hospital for 48 hours after starting treatment. </li> <li>Because amiodarone remains in the body for a long time, monitoring is also needed when the hepatitis C treatment is given to patients who stopped amiodarone treatment within the last few months. </li> <li>Patients who are taking Harvoni or Sovaldi and Daklinza at the same time as amiodarone, with or without other heart medicines, and who experience symptoms such as slow heartbeat, dizziness, faintness, unusual tiredness, shortness of breath or chest pain during treatment should contact their doctor immediately. </li> <li>Patients who have any concerns about their treatment should discuss them with their doctor or pharmacist.</li> </ul> <p><strong>Information for healthcare professionals</strong></p> <ul> <li>Severe bradycardia and heart block have been reported in patients taking amiodarone and Harvoni, or amiodarone and a combination of Sovaldi and Daklinza. Of 8 cases reviewed up to April 2015, one case resulted in fatal cardiac arrest and two required pacemaker intervention. </li> <li>Onset of bradycardia was within 24 hours of initiating hepatitis C treatment in 6 cases and within 2 to 12 days in the other 2 cases. Rechallenge in the context of continued amiodarone treatment resulted in recurrence of symptomatic bradycardia in 2 cases. Recurrence was also seen on rechallenge with the antivirals 8 days after stopping amiodarone, but not 8 weeks after stopping. </li> <li>Amiodarone should only be initiated in patients treated with Harvoni, or Sovaldi plus Daklinza, if other antiarrhythmics are contra-indicated or not tolerated. </li> <li>If concomitant use with amiodarone is unavoidable, patients should be closely monitored, particularly during the first weeks of treatment. Those at high risk of bradyarrhythmia should be monitored in an appropriate clinical setting for 48 hours after starting concomitant treatment. </li> <li>Due to its long half-life, patients who have discontinued amiodarone within the past few months should also be monitored when starting hepatitis C treatment with Harvoni or Sovaldi plus Daklinza. </li> <li>Patients receiving these hepatitis C medicines with amiodarone, with or without other medicines that lower heart rate, should be warned of the symptoms of bradycardia and heart block and should be advised to seek urgent medical advice if they experience them.</li> </ul> <p>The product information for Harvoni, Sovaldi and Daklinza will be updated appropriately. A letter will also be sent to healthcare professionals involved in hepatitis C treatment explaining these risks and the measures to manage them.</p> <p>Because the number of patients taking amiodarone who have been exposed to Harvoni or Sovaldi in combination with Daklinza is unknown, it is not possible to estimate the incidence of occurrence of these events. The mechanism behind the findings has not been established.</p> <p><strong>More about the medicine</strong></p> <p>Harvoni, Sovaldi and Daklinza are among several novel hepatitis C treatments recently evaluated by EMA, which are available as tablets. They have simplified the management of the disease and allow the prospect of curing the infection. Sovaldi (sofosbuvir) was authorised in the EU in January 2014, Daklinza (dataclasvir) in August 2014 and Harvoni (sofosbuvir/ledipasvir) in November 2014.</p> <p>The active substance sofosbuvir blocks the action of an enzyme called ‘NS5B RNA-dependent RNA polymerase’, while dataclasvir and ledipasvir target a protein called ‘NS5A’; by blocking these targets the medicines stop the hepatitis C virus from multiplying and infecting new cells.</p> <p><sup>1</sup>The review was in the context of a “safety signal”. A safety signal is information on a new or incompletely documented adverse event that is potentially caused by a medicine and that warrants further investigation. The presence of a safety signal does not necessarily mean that a medicine has caused the reported adverse event.</p> <p><a href="http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2015/04/news_detail_002313.jsp&mid=WC0b01ac058004d5c1" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-84314220358192255252015-04-24T12:24:00.001-04:002015-04-24T12:24:03.255-04:00Merck’s Pivotal Phase 3 C-EDGE Program Evaluating Grazoprevir/Elbasvir Shows High Sustained Virologic Responses Across Broad Range of Patients with Chronic Hepatitis C Virus Infection<p><em>Data Sets Include Treatment-Naïve, Treatment-Experienced and HIV Co-Infected Patients with Chronic Hepatitis C Virus Genotypes 1, 4 or 6 Infection</em></p> <p><em>Merck Remains on Track to Submit New Drug Application (NDA) to U.S. Food and Drug Administration (FDA) in First Half of 2015</em></p> <p>Friday, April 24, 2015 1:00 am EDT </p> <p>VIENNA--(<a href="http://www.businesswire.com/">BUSINESS WIRE</a>)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first presentations of data from the company’s ongoing <em>C-EDGE</em> pivotal Phase 3 clinical trial program evaluating the investigational once-daily tablet grazoprevir/elbasvir (100mg/50mg) in patients with or without cirrhosis who are infected with chronic hepatitis C virus (HCV) genotypes 1, 4 or 6 (GT1, 4 or 6).<sup>1</sup> Patients in both the HCV infected, treatment-naïve (<em>C-EDGE TN</em>), and HIV/HCV co-infected, treatment-naïve (<em>C-EDGE CO-INFXN</em>) trials treated for 12 weeks achieved rates of sustained virologic response 12 weeks after the completion of treatment (SVR12) of 95 percent (299/316 and 207/218, respectively). In addition, HCV infected, treatment-experienced patients (<em>C-EDGE TE</em>) treated with or without ribavirin (RBV) for 12 weeks achieved SVR12 rates of 94 percent (98/104) and 92 percent (97/105), respectively, and those treated for 16 weeks achieved SVR12 rates of 97 percent (103/106) and 92 percent (97/105), respectively. These data were presented at <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Filc-congress.eu%2F&esheet=51086217&newsitemid=20150423006879&lan=en-US&anchor=The+International+Liver+CongressTM+2015&index=1&md5=8fe8629519690173f979d801b4b43d66">The International Liver Congress<sup>TM </sup>2015</a> – the 50<sup>th</sup> annual congress of the European Association for the Study of the Liver (Abstract #G07, E-Poster P0886 and E-Poster P0887). A paper detailing the findings of <em>C-EDGE TN</em> was published online in the <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fannals.org&esheet=51086217&newsitemid=20150423006879&lan=en-US&anchor=Annals+of+Internal+Medicine&index=2&md5=bcc743784203b2e054ab07a38221817e"><em>Annals of Internal Medicine</em></a> today.</p> <p>“Patients with co-morbidities and varying treatment experiences represent important segments of the chronic hepatitis C population in need of additional innovative treatment options,” said Dr. Eric Lawitz, vice president, scientific and research development, The Texas Liver Institute and clinical professor of medicine, The University of Texas Health Science Center, San Antonio. “These findings are important because they demonstrate that a single pill of grazoprevir/elbasvir taken once-daily achieved consistently high rates of SVR12 in the patient populations studied.”</p> <p><a href="http://lh3.googleusercontent.com/-zTjQo94UHHY/VTpuHtJ0zII/AAAAAAAANRI/wKLtqpJbyC0/s1600-h/Capture%25255B4%25255D.png"><img title="Capture" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="Capture" src="http://lh3.googleusercontent.com/-E9IbLk9b79s/VTpuIVxZ54I/AAAAAAAANRQ/K_-vw9lFgRw/Capture_thumb%25255B2%25255D.png?imgmax=800" width="342" height="425" /></a></p> <p>“At Merck, we continue to build upon our clinical experience using grazoprevir/elbasvir across diverse populations of patients infected with chronic hepatitis C virus,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “We remain on track to submit a New Drug Application with the U.S. Food and Drug Administration in the first half of 2015.”</p> <p><em>C-EDGE TN Overview and Additional Findings</em></p> <p><a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fct2%2Fshow%2FNCT02105467&esheet=51086217&newsitemid=20150423006879&lan=en-US&anchor=C-EDGE+TN&index=3&md5=b7c94eb4172721210d3864b2f87f47c8"><em>C-EDGE TN</em></a> is a randomized, blinded, placebo-controlled trial evaluating the efficacy and safety of grazoprevir/elbasvir in treatment-naïve patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 who received therapy for 12 weeks. Patients were randomized to an immediate treatment group that received grazoprevir/elbasvir for 12 weeks or to a deferred treatment group that received placebo for 12 weeks, were followed for an additional four weeks, and then received open label grazoprevir/elbasvir for the next 12 weeks. The primary efficacy analysis included those patients who received immediate treatment with grazoprevir/elbasvir or placebo. Of the 316 patients who received immediate treatment with grazoprevir/elbasvir, 50 percent were infected with GT1a, 42 percent with GT1b, six percent with GT4 and three percent with GT6. Overall, 22 percent of patients had liver cirrhosis.</p> <p>In this study, virologic failure occurred in 13 patients (4%) in the immediate treatment group, including one virologic breakthrough and 12 virologic relapses. Serious adverse events occurred in nine (3%) and three (3%) patients in the immediate treatment and corresponding placebo arms, respectively; none were considered drug-related. The most common adverse events reported (greater than 5% incidence) in the immediate treatment and corresponding placebo groups, were headache (17%, 18%), fatigue (16%, 17%), nausea (9%, 8%) and arthralgia (6%, 6%), respectively.</p> <p><em>C-EDGE CO-INFXN Overview and Additional Findings</em></p> <p><a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fct2%2Fshow%2FNCT02105662&esheet=51086217&newsitemid=20150423006879&lan=en-US&anchor=C-EDGE+CO-INFXN&index=4&md5=eb113894fc1604c2f716a5dc328dfb9e"><em>C-EDGE CO-INFXN</em></a> is an open label, single-arm study evaluating the efficacy and safety of grazoprevir/elbasvir in treatment-naïve patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 and HIV who received therapy for 12 weeks. Of the 218 patients enrolled in the trial, 66 percent were infected with HCV GT1a, 21 percent with GT1b or other GT1, 13 percent with GT4, and one percent with GT6. Overall, 16 percent of patients had liver cirrhosis.</p> <p>In this study, virologic failure occurred in seven patients (3%), including six virologic relapses and one reinfection. There were no reported drug-related serious adverse events. The most common (greater than 5% incidence) adverse events reported were fatigue (13%), headache (12%) and nausea (9%).</p> <p><em>C-EDGE TE Overview and Additional Findings</em></p> <p><a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fct2%2Fshow%2FNCT02105701&esheet=51086217&newsitemid=20150423006879&lan=en-US&anchor=C-EDGE+TE&index=5&md5=8974217487bbb98970f0787872c368c2"><em>C-EDGE TE</em></a> is a randomized study evaluating the efficacy and safety of once-daily grazoprevir/elbasvir with or without twice-daily RBV in treatment-experienced (prior null response, partial response or relapse with peg-interferon/RBV) patients with or without cirrhosis infected with chronic HCV GT1, 4 or 6 who received therapy for 12 weeks or 16 weeks.</p> <p>12 week arms</p> <p>Of the 209 patients randomized to the 12 week arms, 105 patients received grazoprevir/elbasvir only and 104 patients received grazoprevir/elbasvir plus RBV. Patients in the grazoprevir/elbasvir only arm comprised 58 percent GT1a, 33 percent GT1b or other GT1 and nine percent GT4. Overall, 35 percent had liver cirrhosis. Among the 104 patients receiving grazoprevir/elbasvir plus RBV, 58 percent were infected with chronic HCV GT1a, 28 percent GT1b or other GT1, and 14 percent GT4. Overall, 34 percent had liver cirrhosis.</p> <p>In the grazoprevir/elbasvir only and grazoprevir/elbasvir plus RBV arms, six patients in each arm (6%) were reported to have virologic relapse. No patients were reported to have virologic breakthrough or rebound. Serious adverse events were reported in four patients in the grazoprevir/elbasvir only arm (4%) and three patients in the grazoprevir/elbasvir plus RBV arm (3%). The most common (greater than 10% incidence) adverse events reported in the grazoprevir/elbasvir and grazoprevir/elbasvir plus RBV arms, respectively, were fatigue (19%, 27%), headache (21%, 20%) and nausea (9%, 14%).</p> <p>16 week arms</p> <p>Of the 211 patients enrolled in the 16 week arms, 105 patients received grazoprevir/elbasvir only and 106 patients received grazoprevir/elbasvir plus RBV. In the grazoprevir/elbasvir only arm, 46 percent were infected with chronic HCV GT1a, 46 percent with GT1b or other GT1, five percent with GT4 and four percent with GT6. Overall, 36 percent of patients had liver cirrhosis. Among those in the grazoprevir/elbasvir plus RBV arm, 55 percent were infected with chronic HCV GT1a, 36 percent with GT1b or other GT1, eight percent with GT4, and two percent with GT6. Overall, 35 percent had liver cirrhosis.</p> <p>Among the patients receiving grazoprevir/elbasvir only, three patients (3%) were reported to have virologic breakthrough or rebound and four patients (4%) were reported to have virologic relapse. No virologic failures occurred in patients receiving grazoprevir/elbasvir plus RBV. Serious adverse events were reported in three patients in the grazoprevir/elbasvir only arm (3%) and four patients in the grazoprevir/elbasvir plus RBV arm (4%). The most common (greater than 10% incidence) adverse events reported in the grazoprevir/elbasvir and grazoprevir/elbasvir plus RBV arms, respectively, were fatigue (16%, 30%), headache (19%, 19%) and nausea (4%,17%).</p> <p><strong>About the <em>C-EDGE</em> Program</strong></p> <p><em>C-EDGE </em>is the Phase 3 clinical development program for Merck’s investigational HCV treatment grazoprevir/elbasvir comprising five studies with more than 1,700 patients across more than 25 countries. These studies are evaluating grazoprevir/elbasvir in multiple genotypes (GT1, 4 and 6) and diverse patient populations, including difficult-to-treat patients such as: treatment-experienced, patients with cirrhosis, HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, and those receiving opiate substitution therapies.</p> <p><strong>Merck’s Commitment to HCV</strong></p> <p>For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative health care solutions that support people living with HCV worldwide.</p> <p><strong>About Merck</strong></p> <p>Today’s Merck is a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. For more information, visit <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.merck.com&esheet=51086217&newsitemid=20150423006879&lan=en-US&anchor=www.merck.com&index=6&md5=42308a60d8e0d5b5b07ed3feaf09013d">www.merck.com</a> and connect with us on <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Ftwitter.com%2FMerck&esheet=51086217&newsitemid=20150423006879&lan=en-US&anchor=Twitter&index=7&md5=19af5fbc243277ff389ceb0fd1d41a40">Twitter</a>, <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.facebook.com%2FMerckBeWell&esheet=51086217&newsitemid=20150423006879&lan=en-US&anchor=Facebook&index=8&md5=35aea8df748d399edbc67f71d03ece4b">Facebook</a> and <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.youtube.com%2FMerck&esheet=51086217&newsitemid=20150423006879&lan=en-US&anchor=YouTube&index=9&md5=df590d633c567a2ec7da555c9a885efb">YouTube</a>.</p> <p><strong>Forward-Looking Statement</strong></p> <p>This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.</p> <p>Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.</p> <p>Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise except as required by applicable law. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2014 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (<a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.sec.gov%2F&esheet=51086217&newsitemid=20150423006879&lan=en-US&anchor=www.sec.gov&index=10&md5=0b9dd21daae2ffa83201417b23cbcd92">www.sec.gov</a>).</p> <p><sup>1</sup> Grazoprevir is an HCV NS3/4A protease inhibitor and elbasvir is an HCV NS5A replication complex inhibitor</p> <p><strong>Contact:</strong> </p> <p>Merck <br />Media: <br />Doris Li , 908-246-5701 <br />or <br />Sarra Herzog, 201-669-6570 <br />or <br />Investors: <br />Joe Romanelli, 908-740-1986 <br />or <br />Justin Holko, 908-740-1879</p> <p><a href="http://www.mercknewsroom.com/news-release/hepatitis-c-newsroom/mercks-pivotal-phase-3-c-edge-program-evaluating-grazoprevirelbasv" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-5683544639012832742015-04-24T01:23:00.001-04:002015-04-24T01:23:11.341-04:00Gilead uses Georgia as free-drug testbed for hepatitis C elimination<p>Provided by <a href="http://www.reuters.com/" target="_blank">Reuters</a></p> <p>Health | Wed Apr 22, 2015 11:58am EDT</p> <p align="center"><a href="http://lh3.googleusercontent.com/-XGafcJQz_oc/VTnTPKiCzaI/AAAAAAAANQs/ew2hbc-QTAA/s1600-h/r%25255B5%25255D.jpg"><img title="r" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="r" src="http://lh3.googleusercontent.com/-E9ZCrLwKTjg/VTnTPXXV5QI/AAAAAAAANQw/-WxA3jbA0lo/r_thumb%25255B4%25255D.jpg?imgmax=800" width="342" height="236" /></a></p> <p align="center">Gregg Alton, Gilead's executive vice president, corporate and medical affairs, speaks with the media during a news conference in New Delhi September 15, 2014. </p> <p>LONDON | By <a href="http://blogs.reuters.com/search/journalist.php?edition=us&n=ben.hirschler&">Ben Hirschler</a></p> <p>LONDON (Reuters) - <a href="http://www.reuters.com/finance/stocks/overview?symbol=GILD">Gilead Sciences</a> is seeking to convince governments and multilateral agencies worldwide that hepatitis C can be eliminated with a demonstration project in Georgia offering free drugs to all those who need them.</p> <p>The unprecedented program will make the Caucasian country a testbed for uprooting the liver-destroying disease, using Gilead's highly effective but costly pill Sovaldi, plus its newer product Harvoni once approved.</p> <p>Georgia has the world's third highest prevalence of hepatitis C, after Egypt and Mongolia, with nearly 7 percent of adults carrying the virus. It also has a wide range of viral variations and different types of patients.</p> <p>What is more, the country is a manageable size, with a population of around 5 million, and has viral screening systems, making it ideal for scientific study, according to Gregg Alton, the U.S. drugmaker's head of corporate and medical affairs.</p> <p>"It is a nice country for us to evaluate," he said in a telephone interview on Wednesday from the European Association for the Study of the Liver annual meeting in Vienna.</p> <p>The scheme, which has the backing of the U.S. Centers for Disease Control and Prevention, will cover an initial 5,000 patients in 2015, with a second phase treating up to 20,000 a year.</p> <p>Gilead's hepatitis C drugs, and rival products from the likes of AbbVie, can cure hepatitis C but are out of reach at Western prices to patients in poor countries, with a single Sovaldi pill costing $1,000 in the United States.</p> <p>While Gilead has slashed the price for several low-income countries to $300 per bottle of 28 pills, it also wants to involve international donors in a broad eradication drive.</p> <p>"We will take the Georgia data to other countries around the world to really make the case that investment can fundamentally change the disease over time," Alton said.</p> <p>Alton admits the scheme may prompt other governments to ask for free drugs as well, but he said it was unrealistic to simply give away product globally. Instead, he wants to see international funding along the lines of the Global Fund to Fight AIDS, Tuberculosis and Malaria.</p> <p>"Gilead cannot cure hepatitis C globally on our backs alone. There have to be other players that come in and make that investment," he said.</p> <p>(Editing by William Hardy)</p> <p><a href="http://www.reuters.com/article/2015/04/22/us-health-hepatitis-gilead-georgia-idUSKBN0ND1XU20150422" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-36818559002528881512015-04-24T01:09:00.001-04:002015-04-24T01:09:29.108-04:00U.S. FDA Grants Priority Review to AbbVie for Investigational, All-Oral, Interferon-Free Therapy for the Treatment of Genotype 4 Chronic Hepatitis C<p><a href="http://lh3.googleusercontent.com/-COcqWBj2Hyo/VTnQBWogaDI/AAAAAAAANQY/eGQG1kZOuOs/s1600-h/logo_abbvie%25255B70%25255D.png"><img title="logo_abbvie" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="logo_abbvie" src="http://lh3.googleusercontent.com/-3s84P6PsLX8/VTnQB0o96GI/AAAAAAAANQg/QPDyq6lr2cI/logo_abbvie_thumb%25255B68%25255D.png?imgmax=800" width="237" height="57" /></a></p> <p><em>- The New Drug Application (NDA) was accepted by the U.S. Food and Drug Administration (FDA) and is based on results from the PEARL-I study, which demonstrated up to 100 percent sustained virologic response rates at 12 weeks post-treatment with no discontinuations due to adverse events <br />- First all-oral, interferon-free therapy being evaluated by the FDA for patients with chronic genotype 4 (GT4) hepatitis C virus (HCV) infection <br />- AbbVie's investigational regimen has been previously designated as a breakthrough therapy and received priority review by the FDA</em></p> <p>NORTH CHICAGO, Ill., April 24, 2015 /<a href="http://www.prnewswire.com/">PRNewswire</a>/ -- AbbVie (NYSE: ABBV) has announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) and granted priority review for the company's, all-oral, interferon-free, two direct-acting antiviral treatment of ombitasvir, paritaprevir, ritonavir (OBV/PTV/r), with ribavirin (RBV). The NDA is for the treatment of adults with chronic genotype 4 (GT4) hepatitis C virus (HCV) infection.</p> <p>AbbVie's regimen is the first all-oral, interferon-free therapy being evaluated by the FDA for patients in the United States with chronic GT4 HCV infection. This submission affirms the company's commitment to seeking access to curative* therapy for patients living with chronic HCV infection (*curative is defined as when the virus is no longer detectable in the patient's blood 12 weeks after treatment ends; sustained virologic response [SVR<sub>12</sub>]). </p> <p>The FDA granted priority review to AbbVie for the regimen based in part on data from the PEARL-I study, which was recently published online in <i>The Lancet</i>. The FDA grants priority review designation to investigational therapies that treat a serious condition and, if approved, would provide a significant improvement in safety or effectiveness. This designation shortens the regulatory review period for non-new chemical entity NDAs from the normal 10 months to six months. AbbVie's regimen was also granted a Breakthrough Therapy designation by the FDA on June 30, 2014, a status given to investigational treatments for serious or life-threatening conditions with preliminary clinical evidence that may demonstrate substantial improvement on at least one clinically significant endpoint compared to available therapy.<sup>1</sup></p> <p>"We are pleased that the FDA has granted priority review for our all-oral, interferon-free treatment for patients with chronic GT4 HCV infection," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "Submission of this NDA further underscores AbbVie's commitment to developing therapies to treat a wide range of patients living with chronic HCV infection."</p> <p>PEARL-I is an open-label, Phase 2b study that demonstrated 100 percent of GT4 patients without cirrhosis who were new to therapy (n=42/42) or who had failed previous treatment with pegylated interferon (pegIFN) and RBV (n=49/49) achieved SVR<sub>12</sub> after receiving OBV/PTV/r and RBV for 12 weeks. Additionally, 91 percent of patients who were new to therapy achieved SVR<sub>12</sub> (n=40/44) after taking the treatment without RBV. </p> <p>The Centers for Disease Control and Prevention (CDC) estimates that in the United States, 3.2 million people are chronically infected with HCV.<sup>2</sup> While genotype 1 (GT1) is the most prevalent form of HCV in the U.S., accounting for approximately 73 percent of all cases, GT4 infection accounts for up to 6 percent of HCV infections.<sup>3,4 </sup>Hepatitis C is inflammation of the liver caused by an infection with HCV.<sup>5</sup> It is transmitted when an infected person's blood enters the bloodstream of another person.<sup>6</sup> There are six major HCV genotypes (GT1-6).<sup>7</sup> Presently, there is no vaccine for HCV infection.<sup>2</sup></p> <p><b>About the PEARL-I Study</b></p> <p>PEARL-I is an open-label, Phase 2b study designed to evaluate the safety and efficacy of 12 weeks of treatment with OBV/PTV/r with and without RBV in non-cirrhotic adult patients with chronic GT4 HCV infection who were new to therapy or had failed previous treatment with pegylated interferon and RBV. Treatment-naïve GT4 patients were randomized in a 1:1 ratio to receive OBV/PTV/r with or without RBV. All treatment-experienced GT4 patients received OBV/PTV/r with RBV. In the treatment-naïve group without RBV, on-treatment virologic breakthrough was reported in one patient (2 percent) and two patients (5 percent) experienced post-treatment relapse. There were no virologic failures in the other treatment arms. Patients with GT1b HCV infection were also studied but not included in the efficacy analysis for the NDA submission; the results in patients with GT4 HCV were reported in <i>The Lancet</i>. </p> <p>There were no discontinuations due to adverse events in PEARL-I. The most commonly reported treatment-emergent adverse events (greater than 15 percent in any group) were headache (29-33 percent), asthenia (weakness) (24-33 percent), fatigue (7-18 percent), nausea (9-17 percent) and insomnia (5-16 percent). One patient had a grade 3 liver function test elevation (aspartate aminotransferase [AST] greater than five times the upper limit of normal), which was asymptomatic and resolved during continued dosing. Four patients with hemoglobin decreases (anemia) required RBV dose reductions; however, none of these patients required blood transfusions or medication to boost their red blood cell production. </p> <p><b>About AbbVie's Two Direct-Acting Antiviral HCV Treatment <br /></b>AbbVie's proposed all-oral antiviral treatment consists of the fixed-dose combination of paritaprevir/ritonavir (150/100mg) co-formulated with ombitasvir (25mg) dosed once daily, co-administered with weight-based ribavirin (1000mg or 1200mg in divided doses, twice daily). The combination of two direct-acting antivirals, each with distinct mechanisms of action, targets and inhibits specific HCV proteins in the viral replication process.</p> <p><b>About AbbVie's HCV Clinical Development Program </b> <br />AbbVie's HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating interferon-free, all-oral treatments with and without ribavirin with the goal of achieving high sustained virologic response rates in as many patients as possible. AbbVie's development programs combining two direct-acting antivirals are studying additional hepatitis C virus (HCV) genotypes.</p> <p>Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. Paritaprevir is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of hepatitis C.</p> <p><b>Safety Information </b> <br />Ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) and RBV are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.</p> <p>There are special safety considerations when prescribing these drugs in approved populations.</p> <p>OBV/PTV/r must not be used in patients with severe hepatic impairment or with certain medications, which may result in serious and/or life-threatening events or loss of therapeutic effect. OBV/PTV/r can cause increases in certain liver enzyme levels (ALT) and should be monitored during the first four weeks of treatment, and then as clinically indicated thereafter. Female patients should not take ethinyl estradiol-containing medications during treatment with OBV/PTV/r, as they are at greater risk for liver enzyme elevations when taking these medications. </p> <p>Ritonavir must also not be used in patients with known hypersensitivity to ritonavir or any of its excipients. </p> <p>Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, autoimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score ≥6.</p> <p>See approved product labels for more information.</p> <p><b>About AbbVie <br /></b>AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. AbbVie employs more than 26,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit <a href="http://www.abbvie.com/">www.abbvie.com</a>. Follow <a href="http://twitter.com/abbvie">@abbvie</a> on Twitter or view careers on our <a href="http://www.facebook.com/abbviecareers">Facebook</a> or <a href="http://www.linkedin.com/company/abbvie">LinkedIn</a> page. </p> <p><b>Forward-Looking Statements <br /></b>Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission.  AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.</p> <p><sup>1</sup> U.S. Food and Drug Administration Online. Fact Sheet: Breakthrough Therapies. <a href="http://www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact/significantamendmentstothefdcact/fdasia/ucm329491.htm">http://www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact/significantamendmentstothefdcact/fdasia/ucm329491.htm</a>. Accessed March 20, 2015. <br /><sup>2</sup> Centers for Disease Control and Prevention (CDC). Hepatitis C FAQs for health professionals. <a href="http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm">http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm</a>. Accessed March 10, 2015. <br /><sup>3</sup> O'Leary JG, Davis GL. Hepatitis C. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 9th ed, Vol 1. Philadelphia, PA: Saunders Elsevier. 2010:1313-1335. <br /><sup>4</sup> Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. <i>J Hepatology.</i> 2014;61:S45-S57. <br /><sup>5</sup> Mayo Clinic. Hepatitis C: Definition. <a href="http://www.mayoclinic.org/diseases-conditions/hepatitis-c/basics/definition/con-20030618">http://www.mayoclinic.org/diseases-conditions/hepatitis-c/basics/definition/con-20030618</a>. Accessed November 2013. <br /><sup>6</sup> World Health Organization. Hepatitis C Fact Sheet 2014. <a href="http://www.who.int/mediacentre/factsheets/fs164/en/">http://www.who.int/mediacentre/factsheets/fs164/en/</a>. Accessed April 2014. <br /><sup>7</sup> AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. <a href="http://www.hcvguidelines.org/">http://www.hcvguidelines.org</a>. Accessed March 9, 2015.</p> <p>SOURCE AbbVie</p> <p>For further information: Media: Stefanie Prodouz, +1 (224) 637-0971, stefanie.prodouz@abbvie.com; David Freundel, +1 (847) 937-4522, david.freundel@abbvie.com; Investor Relations: Liz Shea, +1 (847) 935-2211, <a href="mailto:liz.shea@abbvie.com">liz.shea@abbvie.com</a></p> <p><a href="http://abbvie.mediaroom.com/2015-04-23-U-S-FDA-Grants-Priority-Review-to-AbbVie-for-Investigational-All-Oral-Interferon-Free-Therapy-for-the-Treatment-of-Genotype-4-Chronic-Hepatitis-C" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-67968070696276340902015-04-23T14:17:00.001-04:002015-04-23T14:17:35.637-04:00Patients feel stigma, discrimination when living with hepatitis<p><a href="http://lh3.googleusercontent.com/-AlJufQ44zj4/VTk3PGwZVSI/AAAAAAAANP8/_s2KJPB8Pzo/s1600-h/50thcongress%25255B79%25255D.png"><img title="50thcongress" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="50thcongress" src="http://lh3.googleusercontent.com/-r7VVqwHPmxI/VTk3PulaYeI/AAAAAAAANQA/Sw8jhJoLYkA/50thcongress_thumb%25255B77%25255D.png?imgmax=800" width="300" height="72" /></a></p> <p>Provided by <a href="http://www.healio.com/" target="_blank">Healio</a></p> <p>April 23, 2015</p> <p>VIENNA — After receiving their diagnoses, patients with viral hepatitis report suffering stigma and discrimination at the hands of family, friends, employers and even health care practitioners, according to a survey presented at the 2015 International Liver Congress.</p> <p>“Viral hepatitis is not only a silent disease, but also a silencing event,” <strong>Marcelo Naveira, MD</strong>, of Brazil’s Ministry of Health, said during a press conference at the congress. “There is a need for a broad campaign targeting hepatitis awareness and fight against stigma and discrimination. Given the recent advances in therapy, one can be assured that no true progress has been achieved while those infected by viral hepatitis still have to face stigma and discrimination. These effects might last long after virologic response is achieved.”</p> <p>Grupo Otimismo, a support group for people with hepatitis and a nongovernmental organization in Brazil, used an online tool to survey 1,217 people infected with hepatitis B or C, Naveira explained. The 12-question survey looked at discrimination and stigma experienced by patients.</p> <p>When asked who they informed, 94.1% of respondents told family, 73.7% told friends, 57.4% told a partner and 46.1% told coworkers, but only 31.4% told support groups, 9.1% told a social network and 2.1% told no one. Although 72.45% of patients reported those they told had some comprehension of their diagnosis, 48.9% reported overall indifference. </p> <p>After diagnosis, 55.8% of patients reported an effect on self-esteem and 41.4% reported feeling shame. More than 40% of respondents reported their diagnoses affected their jobs, friends and sexual relationships; approximately 10% of respondents were dismissed from their jobs due to their hepatitis. Of those that told family members, 24.6% reported family then avoided physical contact and of those who told friends, 23.8% said those friends stopped inviting them to social events.</p> <p>While 70% of health professionals were reported to treat patients properly, 24.6% reported the practitioners kept a certain distance and 6.9% of respondents were denied care. Patients reported that those places in which discrimination took place were the dentist (21.2%), while getting a manicure/pedicure (17.1%), undergoing tests at a lab (10.8%) or at the gym (4.4%).</p> <p>“Protection against the damage inflicted by viral hepatitis is a matter of public health and basic human rights,” Naveira said. “It troubles us in Brazil — it worries us a lot — that even in a society so open to change, people still have to deal with consequences of disease like viral hepatitis. We assume in other societies that people face those same consequences.” <em>– by Katrina Altersitz</em></p> <p><strong>For More Information:</strong></p> <p>Varaldo CN. Abstract P1275. Presented at: International Liver Congress; April 22-26, 2015; Vienna. </p> <p><strong>Disclosure:</strong> Naveira and Varaldo report no relevant financial relationships. </p> <p><a href="http://www.healio.com/hepatology/viral-hepatitis/news/online/%7Bbb96f2ed-737e-4a27-a240-2baf49680665%7D/patients-feel-stigma-discrimination-when-living-with-hepatitis" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-67191773702722651682015-04-23T14:10:00.001-04:002015-04-23T14:11:54.925-04:00Shorter HCV Tx Works in Advanced Disease<p><a href="http://lh3.googleusercontent.com/-ZYQ374r4ttI/VTk1oO-i4PI/AAAAAAAANPo/t6YQXw_RwQA/s1600-h/50thcongress%25255B63%25255D.png"><img title="50thcongress" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="50thcongress" src="http://lh3.googleusercontent.com/-g-wST5v0GCk/VTk1ojyLhCI/AAAAAAAANPs/HRU2tdQXPNs/50thcongress_thumb%25255B61%25255D.png?imgmax=800" width="300" height="72" /></a></p> <p>Provided by <a href="http://www.medpagetoday.com/" target="_blank">MedPage Today</a><strong><em></em></strong></p> <p><strong><em>Twelve weeks of treatment yielded high efficacy rates in hepatitis C (HCV) patients with advanced liver disease or recurrent HCV after transplant.</em></strong></p> <p>by <a href="mailto:m.smith@medpagetoday.com">Michael Smith </a> <br /><i>North American Correspondent, MedPage Today</i></p> <p>VIENNA -- In hepatitis C virus (HCV) patients with advanced liver disease or recurrent HCV after transplant, 12 weeks of treatment yielded high efficacy rates, a researcher said here.</p> <p>Efficacy did not differ greatly among patients randomly assigned to 12 or 24 weeks of treatment with the fixed-dose combination of ledipasvir/sofosbuvir (Harvoni) given with ribavirin, according to <a href="http://elsevierauthors.com/michaelmanns/">Michael Manns, MD</a>, of Hannover Medical School in Hannover, Germany.</p> <p>And the combination was generally well-tolerated -- an important consideration among the seriously ill patients in the so-called SOLAR-2 trial, Manns told reporters here at the <a href="https://ilc-congress.eu/">annual meeting of the European Association for the Study of the Liver</a>.</p> <p>The study evaluated the safety and efficacy of the therapy in patients with <a href="http://www.mdcalc.com/child-pugh-score-for-cirrhosis-mortality/">Child-Pugh</a> scores of B and C either pre- or post-transplant, or in those whose disease had recurred after transplant but who were Child-Pugh A or had fibrosis scores of F0 through F3.</p> <p>The goal was to compare outcomes with 12 weeks of therapy with those after 24 weeks -- the recommended duration for such patients in Europe, Manns said.</p> <p>For most patients with conditions similar to those in the trial, Manns said, "I would feel comfortable treating for 12 weeks."</p> <p>But most of the 328 patients had genotype 1 disease, and the handful of patients in the study with genotype 4 HCV did not do as well, he noted. For those patients, he said, he would continue to aim for 24 weeks of therapy "depending on tolerability."</p> <p>What to do with the difficult-to-treat patients in the study is a tough question, commented <a href="https://ilc-congress.eu/about-easl/governing-board/">Markus Peck-Radosavljevic, MD</a>, of the Medical University of Vienna and current Secretary General of EASL.</p> <p>On one hand, Peck-Radosavljevic told <em>MedPage Today</em>, the study does show that the treatment "is not endangering" the patients and can lead to cures in most cases.</p> <p>But on the other hand, he said, "there might be a point where you don't do them a favor by making them virus-free."</p> <p>It could happen, he said, that treatment might cure a patient of HCV, leaving him or her ineligible for a transplant but still with a seriously damaged liver.</p> <p>In many cases, he said, it might be better to go ahead with a transplant and count on being able to cure recurrent HCV afterward.</p> <p>Patients in the trial, Manns said, had either genotype 1 or 4 and were stratified into six groups: </p> <ul> <li>Patients without transplant and either Child-Pugh B or Child-Pugh C cirrhosis -- groups 1 and 2 </li> <li>Patients with recurrent HCV after liver transplantation and either without cirrhosis or with Child-Pugh A, B, or C cirrhosis -- groups 3 through 6</li> </ul> <p>The endpoint of the study was sustained virologic response 12 weeks after the end of treatment (SVR<sub>12</sub>).</p> <p>Overall, Manns reported, post-transplant patients without fibrosis or with Child-Pugh A status did equally well with 12 or 24 weeks of therapy -- SVR<sub>12</sub> rates were 95% and 98%, respectively.</p> <p>Patients with Child-Pugh B or C cirrhosis, regardless of transplant status, did less well but, again, treatment duration seemed to have little effect -- 85% with SVR<sub>12</sub> at 12 weeks and 88% at 24 weeks, Manns reported.</p> <p>Differences appeared when the patients were broken down by genotype, however.</p> <p>Among patients with genotype 1 disease, 12- and 24-week SVR<sub>12</sub> rates were 96% and 98% if they had low fibrosis scores or Child-Pugh A cirrhosis, and 88% and 89%, respectively, for those with Child-Pugh B or C cirrhosis.</p> <p>The 18 patients with genotype 4 and less advanced liver damage had SVR<sub>12</sub> rates of 91% and 100% after 12 and 24 weeks of therapy, respectively.</p> <p>But among the 14 patients with genotype 4 and Child-Pugh B and C cirrhosis, 12- and 24-week SVR<sub>12</sub> rates were 57% and 86%, respectively.</p> <p>Most patients reported at least one adverse event, with rates of between 92% and 95%, Manns said, but serious adverse events were much less common -- reported by between 14% and 28% of patients, with more seen among those with more advanced disease.</p> <p>There were no treatment-related adverse events in patients without cirrhosis and nine among those with cirrhosis, including five reports of anemia and one each of falling, vomiting, diarrhea, and hyperbilirubinemia.</p> <p>Although there were 10 deaths, none was considered related to treatment, Manns said.</p> <p><em>The study was supported by Gilead Sciences. Manns disclosed relevant relationships with AbbVie, BI, BMS, Gilead, Janssen, Merck, Novartis, Roche, Idenix, and GSK. Some authors are employees of Gilead.</em></p> <p>Reviewed by <a href="http://www.medpagetoday.com/reviewer.cfm?reviewerid=1008">Henry A. Solomon, MD, FACP, FACC</a> Clinical Associate Professor, Weill Cornell Medical College </p> <p>Primary Source: European Association for the Study of the Liver</p> <p><strong>Source Reference:</strong> Manns M, et al "Ledipasvir/sofosbuvir with ribavirin is safe and efficacious in decompensated and post liver transplantation patients with HCV infection: Preliminary results of the prospective SOLAR 2 trial" EASL 2015; Abstract G02.</p> <p><a href="http://www.medpagetoday.com/MeetingCoverage/EASL/51153" target="_blank">Source</a></p> <p>Also See: <a href="http://hepatitiscresearchandnewsupdates.blogspot.com/2015/04/gileads-harvoni-and-sovaldi-demonstrate.html" target="_blank">Gilead’s Harvoni and Sovaldi Demonstrate Efficacy and Safety among Chronic Hepatitis C Patients with Advanced Liver Disease</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-21787254858355553492015-04-23T14:00:00.001-04:002015-04-23T14:00:43.430-04:00Study reveals impact of delaying HCV treatment<p><a href="http://lh3.googleusercontent.com/-4dpgzoHaks8/VTkzR5xfcRI/AAAAAAAANPU/NvPLl_ZtqE8/s1600-h/50thcongress%25255B65%25255D.png"><img title="50thcongress" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="50thcongress" src="http://lh3.googleusercontent.com/-KEB6LWkH_wg/VTkzSe1NgSI/AAAAAAAANPc/0fRA-2FCzJk/50thcongress_thumb%25255B63%25255D.png?imgmax=800" width="302" height="72" /></a></p> <p>Published on April 23, 2015 at 4:01 AM</p> <p>Data revealed today at The International Liver Congress™ 2015 highlights the impact of delaying treatment for the hepatitis C virus (HCV). Researchers found that treatment delays have a serious detrimental effect on treatment efficacy, increasing the risk of morbidity and mortality among patients.</p> <p>The study was conducted using retrospective patient data from the Veterans Administration in the USA to estimate the impact on risk of morbidity and death depending on whether treatment was initiated before or after a patient's FIB4 levels became elevated. The FIB4 index is a simple formula used to predict liver damage (fibrosis) based on standard biochemical values and age.</p> <p>Researchers found that delaying treatment until after a patient's FIB4 level exceeds 3.25 has a clear detrimental effect on treatment effectiveness. Delaying therapy until after the patient's FIB4 level exceeds 1.45 or 1.00 has a smaller detrimental effect on treatment effectiveness.</p> <p>The study demonstrates that delaying HCV treatment in an attempt to save costs has a serious adverse impact on patients, with the most serious effect being the speeding up of time to death. Once HCV diagnosis has been confirmed the most suitable treatment should be initiated as soon as feasible balancing budgetary cash-flow issues against adverse impacts on patients.</p> <p>Source: European Association for the Study of the Liver</p> <p><a href="http://www.news-medical.net/news/20150423/Study-reveals-impact-of-delaying-HCV-treatment.aspx" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-71235238931385388592015-04-23T12:44:00.001-04:002015-04-23T12:44:39.631-04:00Janssen Announces SVR12 Rates with Twelve Weeks of Treatment with All-Oral, Once-Daily Regimen of Simeprevir Plus Sofosbuvir in Genotype 1 HCV Patients With and Without Cirrhosis<p><a href="http://lh3.googleusercontent.com/-XB_n0_g4c2Y/VTkhdNBxNUI/AAAAAAAANO8/AsHkonJ8Wb0/s1600-h/NY88746LOGO%25255B7%25255D.jpg"><img title="NY88746LOGO" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="NY88746LOGO" src="http://lh3.googleusercontent.com/-j-rQAI7NNQQ/VTkhdZItWaI/AAAAAAAANPA/I7fmHSD-sig/NY88746LOGO_thumb%25255B5%25255D.jpg?imgmax=800" width="152" height="152" /></a></p> <p><em>- Data from OPTIMIST-1 and OPTIMIST-2 Trials Showing SVR12 Rates of 97 Percent and 84 Percent to be Presented at The International Liver Congress™ 2015 of the European Association for the Study of the Liver -</em></p> <p>CORK, Ireland, April 23, 2015 /PRNewswire/ -- Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), today announced results for its hepatitis C treatment simeprevir at The International Liver Congress™ 2015 of the European Association for the Study of the Liver (EASL) in Vienna. Late-breaking results from the Phase 3 OPTIMIST-1 and OPTIMIST-2 trials highlight the clinical outcomes of simeprevir in an all-oral combination regimen in a wide range of patients with hepatitis C virus (HCV) infection.</p> <p>"The new data for simeprevir presented at The International Liver Congress™ confirms its efficacy when combined with sofosbuvir in an all-oral, ribavirin-free regimen for HCV patients, including those who are treatment-naive and treatment-experienced, both with and without cirrhosis," said Gaston Picchio, hepatitis disease area leader, Janssen. "These data further demonstrate the role of simeprevir within the HCV treatment landscape, as it provides patients with an important therapeutic option."</p> <p>The results from the OPTIMIST-1 and OPTIMIST-2 trials are the first Phase 3 data to be presented on simeprevir in combination with sofosbuvir (SMV/SOF) in patients with genotype 1 chronic HCV infection, both with and without cirrhosis. Sofosbuvir is a nucleotide analog NS5B polymerase inhibitor developed by Gilead Sciences, Inc.</p> <p><b><u>OPTIMIST-1</u></b><sup>1</sup></p> <ul> <li>OPTIMIST-1 is a Phase 3, randomized, open-label trial to investigate the efficacy and safety of the all-oral regimen of SMV/SOF among treatment-naive and treatment-experienced genotype 1 chronic HCV-infected patients without cirrhosis. The primary objective was to show superior sustained virologic response (SVR) at 12 weeks after treatment (SVR12) with 12 and eight weeks of treatment with SMV/SOF versus a historical control (patients previously treated with approved regimens containing a direct-acting antiviral, pegylated interferon and ribavirin). </li> <li>Ninety-seven (97) percent of patients treated with SMV/SOF for 12 weeks (n=150/155) achieved SVR12, which was superior to the SVR12 rate of 87 percent among the historical control. <ul> <li>SVR12 rates of 100 percent were seen among patients with IL28B CC genotype (n=43/43) and those with baseline NS5A and NS3 Q80K polymorphisms (n=9/9).</li> </ul> </li> <li>Patients treated with eight weeks of SMV/SOF achieved an SVR12 rate of 83 percent (n=128/155), which was not superior to the SVR12 rate of 83 percent in the historical control. <ul> <li>High SVR12 rates were seen among patients with baseline HCV RNA <4 million IU/mL (96 percent; n=46/48), <i>IL28B</i> CC genotype (93 percent; n=38/41), patients with genotype 1b HCV infection (92 percent; n=36/39) and patients without baseline NS5A and Q80K polymorphisms (89 percent; n=78/88).</li> </ul> </li> <li>The most frequently reported adverse events in the 12-week and eight-week treatment arms were headache (14 and 17 percent, respectively), fatigue (12 and 15 percent, respectively) and nausea (15 and 9 percent, respectively).</li> </ul> <p><b><u>OPTIMIST-2</u></b><sup>2</sup></p> <ul> <li>OPTIMIST-2 is a Phase 3, open-label, single-arm trial to investigate the efficacy and safety of SMV/SOF in treatment-naive and treatment-experienced genotype 1 chronic HCV-infected patients with cirrhosis. The primary objective was to show superior SVR12 with 12 weeks of treatment with SMV/SOF versus a historical control. </li> <li>Twelve (12) weeks of treatment with SMV/SOF resulted in SVR12 rates of 84 percent (n=86/103), which was superior to the SVR12 rate of 70 percent in the historical control.</li> <li>Higher SVR12 rates were seen in patients with baseline NS5A polymorphisms with or without NS3 Q80K polymorphisms (100 percent, n=13/13), patients with albumin ≥4 g/dL (94 percent; n=47/50) and treatment-naïve patients (88 percent; n=44/50). </li> <li>The most common adverse events were fatigue (20 percent), headache (20 percent) and nausea (11 percent).</li> </ul> <p>"Chronic HCV infection is a leading cause of cirrhosis, and once it is developed, these patients can be very difficult to cure. The results of the OPTIMIST-2 study demonstrate the safety and efficacy of the all-oral regimen of simeprevir and sofosbuvir for genotype 1 chronic HCV patients with cirrhosis," said Eric Lawitz, M.D., Texas Liver Institute, principal investigator of the OPTIMIST-2 study.</p> <p><b>About Hepatitis C <br /></b>Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is a major global public health concern. Approximately 170 million people are infected with hepatitis C worldwide and 350,000 people per year die from the disease globally. When left untreated, hepatitis C can cause significant damage to the liver, including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.</p> <p><b>About Janssen's HCV Development Program <br /></b>The goal of the Janssen hepatitis C virus (HCV) clinical development program is to provide physicians with multiple treatment options in order to offer patients the best possible chance at successful therapy.</p> <p>Ongoing studies focus on the investigation of the NS3/4A protease inhibitor simeprevir in a number of different treatment combinations and HCV patient populations, including those who are difficult to cure.</p> <p>Janssen's HCV pipeline also includes JNJ-56914845, an investigational NS5A replication complex inhibitor currently in Phase 2 studies, and following the acquisition of Alios BioPharma by Johnson & Johnson in November 2014, AL-335, a uridine-based nucleotide analog in Phase 1 development, and AL-516, a guanosine-based nucleotide analog NS5B polymerase inhibitor in pre-clinical development.</p> <p>These compounds are being developed with the intent of targeting critical steps of the HCV replication cycle. </p> <p><b>About Simeprevir (OLYSIO</b><b><sup>®</sup></b><b>) <br /></b>Simeprevir is an NS3/4A protease inhibitor which has been developed by Janssen Sciences Ireland UC in collaboration with Medivir AB. </p> <p>In November 2013, simeprevir was initially approved by the U.S. Food and Drug Administration, and in May 2014, it was granted marketing authorization by the European Commission. Subsequent marketing authorizations have followed in several other countries around the world. Indications vary by market.</p> <p>Janssen is responsible for the global clinical development of simeprevir and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB retains marketing rights for simeprevir in these countries under the marketing authorization held by Janssen-Cilag International NV.</p> <p><b>About Janssen Pharmaceutical Companies of Johnson & Johnson <br /></b>At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Janssen R&D Ireland is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit <a href="http://www.janssenrnd.com/">http://www.janssenrnd.com</a> for more information.</p> <p><b>INDICATIONS <br /></b>OLYSIO<sup>® </sup>is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated for the treatment of chronic hepatitis C (CHC) genotype 1 infection as a component of a combination antiviral treatment regimen.</p> <p>Limitations of Use:</p> <ul> <li>OLYSIO<sup>®</sup> monotherapy is not recommended. </li> <li>OLYSIO<sup>®</sup> efficacy in combination with peginterferon alfa (Peg‑IFN‑alfa) and ribavirin (RBV) is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism at baseline compared to patients infected with hepatitis C virus (HCV) genotype 1a without the Q80K polymorphism. Screening patients with HCV genotype 1a infection for the presence of virus with the NS3 Q80K polymorphism at baseline is strongly recommended. Alternative therapy should be considered for patients infected with HCV genotype 1a containing the Q80K polymorphism. </li> <li>OLYSIO<sup>®</sup> is not recommended in patients with moderate or severe hepatic impairment (Child‑Pugh Class B or C). </li> <li>OLYSIO<sup>®</sup> is not recommended in patients who have previously failed therapy with a treatment regimen that included OLYSIO<sup>®</sup> or other HCV protease inhibitors.</li> </ul> <p><b>IMPORTANT SAFETY INFORMATION</b></p> <p><b>C</b><b>ontraindications: </b></p> <ul> <li>There are no specific contraindications to OLYSIO<sup>®</sup>. The contraindications to other antiviral drugs administered with OLYSIO<sup>®</sup> for the treatment of CHC infection also apply to OLYSIO<sup>®</sup> combination treatment.  Prescribers should consult the complete prescribing information for these drugs for a description of contraindications.</li> </ul> <p><b>Warnings and Precautions: </b></p> <ul> <li><b>Serious Symptomatic Bradycardia When Co-administered with Sofosbuvir and Amiodarone:  </b>Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is co-administered with sofosbuvir in combination with another HCV direct acting antiviral, including OLYSIO<sup>®</sup>. A fatal cardiac arrest was reported in a patient receiving a sofosbuvir-containing regimen (ledipasvir/sofosbuvir). Bradycardia has generally occurred within hours to days, but cases have been observed up to 2 weeks after initiating HCV treatment. Patients also taking beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease may be at increased risk for symptomatic bradycardia with co-administration of amiodarone. Bradycardia generally resolved after discontinuation of HCV treatment. The mechanism for this bradycardia effect is unknown.  <br />Co-administration of amiodarone with OLYSIO<sup>®</sup> in combination with sofosbuvir is not recommended. For patients taking amiodarone who have no other alternative treatment options, and who will be co-administered OLYSIO and sofosbuvir:  <br />         o    Counsel patients about the risk of serious symptomatic bradycardia <br />         o    Cardiac monitoring in an in-patient setting for the first 48 hours of <br />               co-administration is recommended, after which outpatient or self-monitoring <br />               of the heart rate should occur on a daily basis through at least the first 2 <br />               weeks of treatment. <br />Patients who are taking sofosbuvir in combination with OLYSIO<sup>®</sup> who need to start amiodarone therapy due to no other alternative treatment options should undergo similar cardiac monitoring as outlined above. <br />Due to amiodarone's long elimination half-life, patients discontinuing amiodarone just prior to starting sofosbuvir in combination with OLYSIO<sup>®</sup> should also undergo similar cardiac monitoring as outlined above. <br />Patients who develop signs or symptoms of bradycardia should seek medical evaluation immediately. Symptoms may include near-fainting or fainting, dizziness or lightheadedness, malaise, weakness, excessive tiredness, shortness of breath, chest pain, confusion or memory problems. </li> <li><b>Hepatic Decompensation and Hepatic Failure</b>:  Hepatic decompensation and hepatic failure, including fatal cases, have been reported postmarketing in patients treated with OLYSIO<sup>®</sup> in combination with Peg‑IFN‑alfa and RBV or in combination with sofosbuvir.  Most cases were reported in patients with advanced and/or decompensated cirrhosis who are at increased risk for hepatic decompensation or hepatic failure.  Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between treatment with OLYSIO<sup>®</sup> and these events has not been established. <br />OLYSIO<sup>®</sup> is not recommended for patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). <br />In clinical trials of OLYSIO<sup>®</sup>, modest increases in bilirubin levels were observed without impacting hepatic function. Postmarketing cases of hepatic decompensation with markedly elevated bilirubin levels have been reported.  Monitor liver chemistry tests before and as clinically indicated during OLYSIO<sup>®</sup> combination therapy.  Patients who experience an increase in total bilirubin to greater than 2.5 times the upper limit of normal should be closely monitored: <ul> <li>Patients should be instructed to contact their healthcare provider if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice or discolored feces. </li> <li>Discontinue OLYSIO if elevation in bilirubin is accompanied by liver transaminase increases or clinical signs and symptoms of hepatic decompensation. </li> </ul> </li> <li><b>Risk of Serious Adverse Reactions Associated With Combination Treatment</b>: OLYSIO<sup>®</sup> should be used in combination with other antiviral drugs for the treatment of CHC infection. Therefore, consult the prescribing information for these drugs before starting therapy with OLYSIO<sup>®</sup>. </li> <li><b>Photosensitivity</b><b>: </b>Photosensitivity reactions have been observed with OLYSIO<sup>®</sup> combination therapy. Serious photosensitivity reactions resulting in hospitalization have been observed with OLYSIO<sup>®</sup> in combination with Peg‑IFN‑alfa and RBV. Photosensitivity reactions occurred most frequently in the first 4 weeks of treatment, but can occur at any time during treatment. Photosensitivity may present as an exaggerated sunburn reaction, usually affecting areas exposed to light (typically the face, "V" area of the neck, extensor surfaces of the forearms, and dorsa of the hands). Manifestations may include burning, erythema, exudation, blistering, and edema. <br />Use sun protective measures and limit sun exposure during treatment with OLYSIO<sup>®</sup>. Avoid use of tanning devices during treatment with OLYSIO<sup>®</sup>. Discontinuation of OLYSIO<sup>®</sup> should be considered if a photosensitivity reaction occurs and patients should be monitored until the reaction has resolved. If a decision is made to continue OLYSIO<sup>®</sup> in the setting of a photosensitivity reaction, expert consultation is advised. </li> <li><b>Rash</b><b>:</b> Rash has been observed with OLYSIO<sup>®</sup> combination therapy. Rash occurred most frequently in the first 4 weeks of treatment, but can occur at any time during treatment. Severe rash and rash requiring discontinuation of OLYSIO<sup>®</sup> have been reported in subjects receiving OLYSIO<sup>®</sup> in combination with Peg‑IFN‑alfa and RBV. Most of the rash events in OLYSIO<sup>®</sup>‑treated patients were of mild or moderate severity. Patients with mild to moderate rashes should be followed for possible progression of rash, including the development of mucosal signs (e.g., oral lesions, conjunctivitis) or systemic symptoms. If the rash becomes severe, OLYSIO<sup>®</sup> should be discontinued. Patients should be monitored until the rash has resolved. </li> <li><b>Sulfa Allergy</b><b>: </b>OLYSIO<sup>®</sup> contains a sulfonamide moiety. In subjects with a history of sulfa allergy (n=16), no increased incidence of rash or photosensitivity reactions has been observed. However, there are insufficient data to exclude an association between sulfa allergy and the frequency or severity of adverse reactions observed with the use of OLYSIO<sup>®</sup>. </li> <li><b>Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions</b><b>: </b>Co‑administration of OLYSIO<sup>®</sup> with substances that are moderate or strong inducers or inhibitors of cytochrome P450 3A (CYP3A) is not recommended as this may lead to significantly lower or higher exposure of simeprevir, respectively, which may result in reduced therapeutic effect or adverse reactions.</li> </ul> <p><b>A</b><b>dverse Reactions</b></p> <ul> <li><b>Use with Peg-IFN-alfa and RBV:</b> Adverse reactions (all grades, at least 3% higher frequency) for OLYSIO<sup>®</sup> with Peg-IFN-alfa and RBV vs. Peg-IFN-alfa and RBV alone in the first 12 weeks were rash (including photosensitivity) (28% vs. 20%), pruritus (22% vs. 15%), nausea (22% vs. 18%), myalgia (16% vs. 13%), and dyspnea (12% vs. 8%).</li> </ul> <ul> <li><b>Use with sofosbuvir:</b> The most common (> 10%) adverse reactions reported during 12 weeks treatment with OLYSIO<sup>®</sup> in combination with sofosbuvir without RBV were fatigue (25%), headache (21%), nausea (21%), insomnia (14%) and pruritus (11%). Rash and photosensitivity were reported in 11% and 7% of subjects, respectively. During 24 weeks treatment with OLYSIO<sup>®</sup> in combination with sofosbuvir, dizziness (16%), and diarrhea (16%) were also commonly reported.</li> </ul> <p><b>Use in Specific Populations</b></p> <ul> <li><b>Pregnancy Category C</b>: Adequate and well-controlled trials with OLYSIO<sup>®</sup> have not been conducted in pregnant women. OLYSIO<sup>®</sup> should be used during pregnancy only if the potential benefit justifies the potential risk. Female patients of childbearing potential should use an effective contraceptive method.</li> </ul> <ul> <li><b>Race</b><b>:</b> Patients of East Asian ancestry exhibit higher simeprevir exposures. In clinical trials, higher simeprevir exposures have been associated with increased frequency of adverse reactions, including rash and photosensitivity. There are insufficient safety data to recommend an appropriate dose for patients of East Asian ancestry. The potential risks and benefits of OLYSIO<sup>®</sup> should be carefully considered prior to use in patients of East Asian ancestry.</li> </ul> <ul> <li><b>Renal Impairment</b><b>:  </b>No dose adjustment of OLYSIO<sup>®</sup> is required in patients with mild, moderate or severe renal impairment. The safety and efficacy of OLYSIO<sup>®</sup> have not been studied in HCV‑infected patients with severe renal impairment (creatinine clearance below 30 mL/min) or end‑stage renal disease, including patients requiring dialysis. Simeprevir is highly protein-bound; therefore, dialysis is unlikely to result in significant removal of simeprevir.</li> </ul> <ul> <li><b>Hepatic Impairment:</b> No dose adjustment of OLYSIO<sup>®</sup> is required in patients with mild hepatic impairment (Child‑Pugh Class A). The safety and efficacy of OLYSIO<sup>®</sup> have not been established in HCV‑infected patients with moderate or severe hepatic impairment (Child‑Pugh Class B or C). OLYSIO<sup>®</sup> is not recommended for patients with moderate or severe hepatic impairment (Child‑Pugh Class B or C). There have been postmarketing reports of hepatic decompensation, hepatic failure, and death in patients with advanced or decompensated cirrhosis receiving OLYSIO<sup>®</sup> combination therapy. Simeprevir exposures are increased in patients with moderate or severe hepatic impairment (Child‑Pugh Class B or C). In clinical trials, higher simeprevir exposures have been associated with increased frequency of adverse reactions, including increased bilirubin, rash and photosensitivity.</li> </ul> <ul> <li><b>Other HCV Genotypes</b><b>:</b> The safety and efficacy of OLYSIO<sup>®</sup> have not been established in patients infected with other HCV genotypes.</li> </ul> <ul> <li><b>Liver Transplantation</b><b>:</b> The safety and efficacy of OLYSIO<sup>®</sup> have not been studied in liver transplant patients.</li> </ul> <p>Not a complete list of Uses in Specific Populations.</p> <p>Consult the PI for Peg-IFN-alfa and RBV or sofosbuvir before starting therapy with OLYSIO<sup>®</sup>.  Safety information related to these drugs also applies to their use in OLYSIO<sup>®</sup> combination treatment.</p> <p>Please see <a href="http://www.olysio.com/shared/product/olysio/prescribing-information.pdf"><b>full Prescribing Information</b></a> and <a href="http://www.olysio.com/shared/product/olysio/patient-information.pdf"><b>Patient Information</b></a> for more details.</p> <p>This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen R&D Ireland and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in new product development, including the uncertainty of clinical success and of obtaining regulatory approvals; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 28, 2014, including in Exhibit 99 thereto, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at <a href="http://www.sec.gov/">www.sec.gov</a>, <a href="http://www.jnj.com/">www.jnj.com</a> or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies or Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.</p> <p><b>References</b></p> <p><sup>1 </sup>A Phase 3, randomised, open-label study to evaluate the efficacy and safety of 12 and 8 weeks of treatment with simeprevir plus sofosbuvir in treatment-naive and -experienced patients with chronic HCV genotype 1 infection without cirrhosis: The OPTIMIST-1 study. Presented at The International Liver Congress™ 2015.</p> <p><sup>2</sup> A Phase 3, open-label, single-arm study to evaluate the efficacy and safety of 12 weeks of simeprevir plus sofosbuvir in treatment-naive or –experienced patients with chronic hepatitis c virus genotype 1 infection and cirrhosis: The OPTIMIST-2 study. Presented at The International Liver Congress™ 2015.</p> <p>Media Contact: Ronan Collins (Global) <br />Mobile: +47 488 425 00</p> <p>Media Contact: Lisa Vaga (United States) <br />Mobile: +1 (908) 670-0363</p> <p>Investor Contact: Lesley Fishman <br />Office: +1 (732) 524 2524</p> <p>Investor Contact: Louise Mehrotra <br />Office: +1 (732) 524 6491</p> <p>Logo - <a href="http://photos.prnewswire.com/prnh/20140324/NY88746LOGO">http://photos.prnewswire.com/prnh/20140324/NY88746LOGO</a></p> <p>SOURCE Janssen Sciences Ireland UC</p> <p>RELATED LINKS <br /><a href="http://www.janssenrnd.com">http://www.janssenrnd.com</a></p> <p><a href="http://www.prnewswire.com/news-releases/janssen-announces-svr12-rates-with-twelve-weeks-of-treatment-with-all-oral-once-daily-regimen-of-simeprevir-plus-sofosbuvir-in-genotype-1-hcv-patients-with-and-without-cirrhosis-300070747.html" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-77258466066041736132015-04-23T12:36:00.001-04:002015-04-23T12:36:56.146-04:00Merck Announces Results from Phase 2/3 Study of Investigational Chronic Hepatitis C Therapy Grazoprevir/Elbasvir in Patients with Advanced Chronic Kidney Disease<p><a href="http://lh3.googleusercontent.com/-TsDIixODPlU/VTkfpCWlYhI/AAAAAAAANOo/aAaXJHc-p-0/s1600-h/logo_Merck_no_be_well%25255B81%25255D.jpg"><img title="logo_Merck_no_be_well" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="logo_Merck_no_be_well" src="http://lh3.googleusercontent.com/-aEiyynx_xPA/VTkfpgI1C9I/AAAAAAAANOs/YIIYTXKs91Y/logo_Merck_no_be_well_thumb%25255B79%25255D.jpg?imgmax=800" width="203" height="64" /></a></p> <p><i>C-SURFER</i> Trial is First to Investigate an All-Oral Ribavirin-Free Hepatitis C Treatment Regimen in Treatment-Naïve and Treatment-Experienced Patients with Advanced Chronic Kidney Disease Infected with Hepatitis C Virus Genotype 1 </p> <p>Thursday, April 23, 2015 3:30 am EDT </p> <p>VIENNA--(<a href="http://www.businesswire.com/">BUSINESS WIRE</a>)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first presentation of data from <i>C-SURFER</i>, the company’s Phase 2/3 clinical trial evaluating the investigational once-daily treatment regimen of grazoprevir (100mg) and elbasvir (50mg) in patients with advanced chronic kidney disease (CKD) infected with chronic hepatitis C virus (HCV) genotype 1 (GT1).<sup>1</sup> Treatment-naïve patients and patients who failed prior pegylated interferon HCV therapy, with or without cirrhosis, all of whom had CKD stages 4 or 5, were enrolled.<sup>2</sup> Following 12 weeks of treatment with grazoprevir and elbasvir, 99 percent (115/116) of patients in the pre-specified primary population for analysis of efficacy data achieved a sustained virologic response 12 weeks after the completion of treatment (SVR12).<sup>3</sup> These data will be presented today at <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Filc-congress.eu%2F&esheet=51085574&newsitemid=20150423005068&lan=en-US&anchor=The+International+Liver+CongressTM+2015&index=1&md5=2970199627f944945a9ef8756bdf26d8">The International Liver Congress<sup>TM </sup>2015</a> – the 50<sup>th</sup> annual congress of the European Association for the Study of the Liver (late breaking E-Poster #LP02). </p> <p>“There is an unmet medical need to treat chronic hepatitis C virus infection in patients with advanced chronic kidney disease,” said Dr. Howard Monsour, Jr., chief of hepatology, Houston Methodist Hospital, Houston, Texas. “In this trial, the first to investigate an all-oral ribavirin-free treatment regimen in treatment-naïve and treatment-experienced CKD patients, treatment with grazoprevir and elbasvir for 12 weeks was effective in this study population with HCV genotype 1 infection.” </p> <p>The ongoing <i>C-SURFER</i> Phase 2/3 clinical trial is a randomized, parallel-group, placebo-controlled study evaluating patients infected with chronic HCV GT1 with advanced CKD with or without liver cirrhosis. Patients were randomized to one of two study arms: </p> <ul> <li>Immediate treatment group (ITG), grazoprevir plus elbasvir (blinded) once-daily for 12 weeks (n=111); </li> <li>Deferred treatment group (DTG), initially placebo (control arm) for 12 weeks followed by a four week follow-up period and then treatment with grazoprevir plus elbasvir (open label) once-daily for 12 weeks (n=113). </li> </ul> <p>In addition, 11 patients received grazoprevir plus elbasvir (open label) once-daily for 12 weeks with intensive pharmacokinetic sampling. </p> <p>Of the 122 patients who received grazoprevir plus elbasvir, 83 percent were treatment-naïve, 36 percent had diabetes, 18 percent had stage 4 CKD, 82 percent had stage 5 CKD, 75 percent were receiving hemodialysis and 45 percent were African-American. Among those patients who received at least one dose of grazoprevir plus elbasvir, five percent (6/122) were excluded from the pre-specified primary efficacy analysis population, or modified full analysis set, due to missing data caused by death or early discontinuation for reasons unrelated to study drug. In the modified full analysis set, 99 percent (115/116) of patients receiving grazoprevir plus elbasvir achieved SVR12. One GT1b infected, non-cirrhotic, interferon-intolerant patient showed a viral relapse at follow-up week 12. Within the modified full analysis set, efficacy was consistent across the patient sub-populations assessed. In a supportive analysis of all 122 patients who received at least one dose of grazoprevir plus elbasvir in the ITG arms, including patients who did not complete the study for reasons not related to study drug, 94 percent (115/122) of patients achieved SVR12. </p> <p>“Merck’s broad clinical development program includes studies dedicated to bringing a once-daily regimen to diverse populations of patients infected with chronic HCV, including certain types of patients with co-morbidities, such as advanced chronic kidney disease,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “These data highlight how emerging innovations in chronic hepatitis C treatment may lead to new options for patient populations in which it historically has been difficult to achieve high rates of sustained viral clearance.” </p> <p>No patients in the ITG arms discontinued treatment due to adverse events (AEs), while four percent (5/113) of patients in the comparator placebo phase of the DTG arm discontinued treatment due to AEs. The rates of serious AEs reported were 14 percent (16/111) in the ITG arms and 17 percent (19/113) in the placebo control DTG arm. The most common treatment-related AEs in the ITG arms and DTG arm (placebo) were headache (17%, 17%), nausea (15%, 16%) and fatigue (10%, 15%), respectively. There were four deaths reported during the initial treatment phase and the first 14 days of study follow-up. One patient (1%) in the open label arm died from cardiac arrest (not considered related to study medicine) and three patients (2%) in the placebo group died from aortic aneurysm, pneumonia and an unknown cause. </p> <p>On April 8, 2015, the company announced that the U.S. Food and Drug Administration (FDA) had granted Breakthrough Therapy designation to grazoprevir/elbasvir for the treatment of patients infected with chronic HCV GT1 with end-stage renal disease on hemodialysis and patients infected with chronic HCV GT4. Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. </p> <p><b>About <i>C-SURFER</i></b></p> <p><a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fct2%2Fshow%2FNCT02092350&esheet=51085574&newsitemid=20150423005068&lan=en-US&anchor=C-SURFER&index=2&md5=865decb1e26af759585ac4e1da7dba47"><i>C-SURFER</i></a> is a Phase 2/3 clinical trial<i> </i>evaluating Merck’s investigational grazoprevir plus elbasvir in patients infected with chronic HCV GT1 and with advanced chronic kidney disease (stages 4 and 5, including patients on hemodialysis) with or without liver cirrhosis, which are among those with HCV infection who are most difficult to treat, over 12 weeks. </p> <p><b>About Chronic HCV Infection and Chronic Kidney Disease</b></p> <p>Chronic HCV infection is both a cause and complication of the treatment of CKD. In patients with CKD, chronic HCV infection is associated with an increased risk of accelerated loss of remaining kidney function, kidney transplant failure and death. Furthermore, patients with chronic HCV infection and advanced CKD represent an unmet need due to a lack of demonstrated HCV treatment options for this group. </p> <p><b>About Grazoprevir/Elbasvir</b></p> <p>Grazoprevir/elbasvir is an investigational, once-daily single tablet regimen consisting of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A replication complex inhibitor). As part of Merck’s broad clinical trials program, grazoprevir/elbasvir is being studied in multiple HCV genotypes and in patients with difficult-to-treat conditions such as HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, liver cirrhosis and those on opiate substitution therapy. </p> <p><b>Merck’s Commitment to HCV</b></p> <p>For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative health care solutions that support people living with HCV worldwide. </p> <p><b>About Merck</b></p> <p>Today’s Merck is a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. For more information, visit <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.merck.com&esheet=51085574&newsitemid=20150423005068&lan=en-US&anchor=www.merck.com&index=3&md5=215e4e99d8c5c3929d0941145c736fbb">www.merck.com</a> and connect with us on <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Ftwitter.com%2FMerck&esheet=51085574&newsitemid=20150423005068&lan=en-US&anchor=Twitter&index=4&md5=ef22779fb545c670169b5e84dad82939">Twitter</a>, <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.facebook.com%2FMerckBeWell&esheet=51085574&newsitemid=20150423005068&lan=en-US&anchor=Facebook&index=5&md5=5694b80cc1474e179228c33a73db5bca">Facebook</a> and <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.youtube.com%2FMerck&esheet=51085574&newsitemid=20150423005068&lan=en-US&anchor=YouTube&index=6&md5=9cf0fe51fe35898a0d2d3954f24e2d77">YouTube</a>. </p> <p><b>Forward-Looking Statement</b></p> <p>This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. </p> <p>Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. </p> <p>Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise except as required by applicable law. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2014 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (<a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.sec.gov&esheet=51085574&newsitemid=20150423005068&lan=en-US&anchor=www.sec.gov&index=7&md5=776415f4ff9f0e23912bf993b6aaabc6">www.sec.gov</a>). </p> <p><sup>1</sup> In Phase 2 studies, grazoprevir/elbasvir are administered as two separate tablets </p> <p><sup>2</sup> Stages 4 and 5 chronic kidney disease are defined as severely or very severely reduced kidney function, based on estimated glomerular filtration rate <30 mL/min/1.73m<sup>2</sup></p> <p><sup>3</sup> Includes patients who received ≥1 dose of study drug and excluded those with missing data because of death or early discontinuation for reasons unrelated to study drug </p> <p><strong><img alt="" src="http://cts.businesswire.com/ct/CT?id=bwnews&sty=20150423005068r1&sid=hq1sc1&distro=nx&lang=en" />Contact:</strong> </p> <p>Media: <br />Doris Li, 908-246-5701 <br />or <br />Sarra Herzog, 201-669-6570 <br />or <br />Investors: <br />Joe Romanelli, 908-740-1986 <br />or <br />Justin Holko, 908-740-1879 </p> <p><a href="http://www.mercknewsroom.com/news-release/hepatitis-c-newsroom/merck-announces-results-phase-23-study-investigational-chronic-hep" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-68734392028664043022015-04-23T11:59:00.001-04:002015-04-23T11:59:59.050-04:00Civacir can effectively prevent HCV recurrence following liver transplants<p><a href="http://lh3.googleusercontent.com/-UPfhx9Pecqk/VTkWudUkFbI/AAAAAAAANOQ/YVHaQ38D1k8/s1600-h/50thcongress%25255B109%25255D.png"><img title="50thcongress" style="border-left-width: 0px; border-right-width: 0px; background-image: none; border-bottom-width: 0px; padding-top: 0px; padding-left: 0px; display: inline; padding-right: 0px; border-top-width: 0px" border="0" alt="50thcongress" src="http://lh3.googleusercontent.com/-C400HJuoIvk/VTkW_aeoa9I/AAAAAAAANOY/fHfV1BUauUY/50thcongress_thumb107.png?imgmax=800" width="344" height="83" /></a></p> <p>Published on April 23, 2015 at 6:50 AM</p> <p>New data from an ongoing Phase III trial revealed today at The International Liver CongressTM 2015 show that the use of hepatitis C immune globulin (HCIG, Civacir®) can effectively prevent hepatitis C virus (HCV) recurrence in patients following a liver transplant (LT). The data demonstrate that intravenous Civacir given both peri- and post-LT prevents HCV-reinfection in patients who also received antiviral therapy (AVT) before their transplant operation.</p> <p>Civacir is a hepatitis C immune globulin (HCIG) produced from pooled plasma from hundreds of screened donors who have high antibody titers against HCV. In this trial, patients received AVT before their LT and those in the active treatment groups received 16 infusions of Civacir in the peri- and immediate post-LT period for 10 weeks. The control group received current standard of care (no treatment) post-LT.</p> <p>The preliminary results suggest that Civacir provides an effective alternative approach as compared to current standard of care to prevent HCV recurrence in post-LT patients. Civacir was well tolerated with no drug-related serious adverse events observed during the study.</p> <p>Hepatitis C virus (HCV) remains the leading cause for liver transplantation (LT) and recurrent HCV disease is the most frequent cause of graft loss. Prevention of recurrence independent of genotype and severity of cirrhosis is highly desirable because it simplifies post-LT management.</p> <p>Source: European Association for the Study of the Liver</p> <p><a href="http://www.news-medical.net/news/20150423/Civacir-can-effectively-prevent-HCV-recurrence-following-liver-transplants.aspx" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-53105299270808989612015-04-23T11:53:00.001-04:002015-04-23T17:33:29.614-04:00All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study<p><em>Hepatology</em></p> <p><a href="http://onlinelibrary.wiley.com/doi/10.1002/hep.v61.4/issuetoc" target="_blank">Volume 61, Issue 4</a> <br />April 2015 <br />Pages 1127–1135 </p> <p><font style="font-weight: normal">David R. Nelson, James N. Cooper, Jacob P. Lalezari, Eric Lawitz, Paul J. Pockros, Norman Gitlin, Bradley F. Freilich, Ziad H. Younes, William Harlan, Reem Ghalib, Godson Oguchi, Paul J. Thuluvath, Grisell Ortiz-Lasanta, Mordechai Rabinovitz, David Bernstein, Michael Bennett, Trevor Hawkins, Natarajan Ravendhran, Aasim M. Sheikh, Peter Varunok, Kris V. Kowdley, Delphine Hennicken, Fiona McPhee, Khurram Rana, Eric A. Hughes, on behalf of the ALLY-3 Study Team</font></p> <p>First published: 10 March 2015 </p> <p>DOI: 10.1002/hep.27726 </p> <p><em>Potential conflict of interest: Dr. Nelson received grants from Bristol-Myers Squibb, Gilead, and Merck. Dr. Lawitz consults, advises, is on the speakers' bureau for, and received grants from AbbVie, Gilead, Janssen, Merck, and Vertex. He consults, advises, and received grants from Achillion, Bristol-Myers Squibb, Idenix, Novartis, Santaris, and Theravance. He consults and advises BioCryst, Biotica, and Regulus. He is on the speakers' bureau for Kadmon. He received grants from Boehringer Ingelheim, GlaxoSmithKline, Presidio, and Roche. Dr. Pockros consults, advises, is on the speakers' bureau for, and received grants from Bristol-Myers Squibb, Gilead, and Janssen. Dr. Gitlin is on the speakers' bureau for and received grants from Bristol-Myers Squibb and Gilead. Dr. Freilich received grants from Bristol-Myers Squibb. Dr. Younes is on the speakers' bureau for and received grants from Vertex, Gilead, and AbbVie. He received grants from Bristol-Myers Squibb, Idenix, and Merck. Dr. Ghalib received grants from Gilead, AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Salix, Pharmasset, Boehringer Ingelheim, Anadys, Janssen, Evoke, Idenix, Takeda, Vertex, Virochem, Achillion, and Debio. Dr. Thuluvath is on the speakers' bureau and received grants from Gilead and AbbVie. He is on the speakers' bureau for Onyx. He received grants from Salix and Bristol-Myers Squibb. Dr. Bernstein consults, advises, is on the speakers' bureau for, and received grants from Gilead and AbbVie. He consults and received grants from Bristol-Myers Squibb. Dr. Hawkins consults, advises, is on the speakers' bureau for, and received grants from Gilead, AbbVie, and Janssen. He is on the speakers' bureau and received grants from ViiV. He received grants from Bristol-Myers Squibb. Dr. Ravendhran advises, is on the speakers' bureau for, and received grants from Gilead and AbbVie. He is on the speakers' bureau for Salix and Onyx. He received grants from Bristol-Myers Squibb and Merck. Dr. Sheikh advises, is on the speakers' bureau for, and received grants from Gilead. He advises and is on the speakers' bureau for AbbVie. He received grants from Bristol-Myers Squibb, Idenix, Merck, Achillion, Vertex, Genentech, and Hologic. Dr. Kowdley advises and received grants from AbbVie, Gilead, Merck, and Bristol-Myers Squibb. He advises Achillion and Trio Health. He received grants from Beckman, Boehringer Ingelheim, Ikaria, Intercept, Janssen, Mochida, Novartis, and Vertex. Dr. Hennicken is employed by Bristol-Myers Squibb. Dr. McPhee is employed by and owns stock in Bristol-Myers Squibb. Dr. Rana is employed by Bristol-Myers Squibb. Dr. Hughes is employed by Bristol-Myers Squibb.</em></p> <p><em>This study was funded by Bristol-Myers Squibb.</em></p> <p><strong>Abstract</strong></p> <p>Treatment options for patients with hepatitis C virus (HCV) genotype 3 infection are limited, with the currently approved all-oral regimens requiring 24-week treatment and the addition of ribavirin (RBV). This phase III study (ALLY-3; <a href="http://clinicaltrials.gov/">ClinicalTrials.gov</a>: NCT02032901) evaluated the 12-week regimen of daclatasvir (DCV; pangenotypic nonstructural protein [NS]5A inhibitor) plus sofosbuvir (SOF; pangenotypic NS5B inhibitor) in patients infected with genotype 3. Patients were either treatment naïve (n = 101) or treatment experienced (n = 51) and received DCV 60 mg plus SOF 400 mg once-daily for 12 weeks. Coprimary endpoints were the proportions of treatment-naïve and treatment-experienced patients achieving a sustained virological response (SVR) at post-treatment week 12 (SVR12). SVR12 rates were 90% (91 of 101) and 86% (44 of 51) in treatment-naïve and treatment-experienced patients, respectively; no virological breakthrough was observed, and ≥99% of patients had a virological response (VR) at the end of treatment. SVR12 rates were higher in patients without cirrhosis (96%; 105 of 109) than in those with cirrhosis (63%; 20 of 32). Five of seven patients who previously failed treatment with an SOF-containing regimen and 2 of 2 who previously failed treatment with an alisporivir-containing regimen achieved SVR12. Baseline characteristics, including gender, age, HCV-RNA levels, and <em>interleukin-28B</em> genotype, did not impact virological outcome. DCV plus SOF was well tolerated; there were no adverse events (AEs) leading to discontinuation and only 1 serious AE on-treatment, which was unrelated to study medications. The few treatment-emergent grade 3/4 laboratory abnormalities that were observed were transient. <em>Conclusion</em>: A 12-week regimen of DCV plus SOF achieved SVR12 in 96% of patients with genotype 3 infection without cirrhosis and was well tolerated. Additional evaluation to optimize efficacy in genotype 3–infected patients with cirrhosis is underway. (Hepatology 2015;61:1127–1135)</p> <p>Chronic infection with hepatitis C virus (HCV) genotype 3 is common throughout the world and remains a significant disease burden for many patients.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0001">1, 2</a>] Infection with HCV genotype 3 has been associated with an increased risk of progression to cirrhosis, as well as development of steatosis or hepatocellular carcinoma (HCC), compared with other HCV genotypes.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0003">3-5</a>] In an observational cohort study, analysis of real-world data from the Veterans Affairs HCV clinical registry found that the risks of cirrhosis, HCC, liver-related hospitalization, and death were significantly higher in genotype 3–infected patients, compared with genotype 1–infected patients,[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0006">6</a>] underscoring the medical need for safe, effective treatment options for patients with genotype 3 infection. Recent advances have led to the approval of interferon (IFN)-free and/or ribavirin (RBV)-free therapies for chronic infection with HCV genotypes 1, 2, 3, and 4. However, for both treatment-naïve and treatment-experienced patients with genotype 3 infection, IFN- and RBV-free therapy options are currently limited.</p> <p>Therapies approved in the United States and Europe for treatment of genotype 3 infection include a 24-week, all-oral regimen of sofosbuvir (SOF; a pangenotypic nonstructural protein [NS]5B inhibitor) in combination with RBV[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0007">7, 8</a>] and a 24-week regimen of pegylated IFN (Peg-IFN) plus RBV.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0009">9, 10</a>] In addition, a 12-week, IFN-based regimen of SOF plus Peg-IFN and RBV[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0008">8</a>] is approved in Europe for treating genotype 3 infection, as are all-oral, 24-week regimens of daclatasvir (DCV; a potent, pangenotypic NS5A inhibitor) plus SOF with RBV[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0011">11</a>] and ledipasvir (LDV; an NS5A inhibitor) plus SOF with RBV[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0012">12</a>] for patients with compensated cirrhosis and/or previous treatment experience. The all-oral combination of SOF plus RBV requires 24 weeks of treatment because 12- and 16-week treatment durations were associated with lower response rates (30%-61% and 62%, respectively) in genotype 3–infected patients.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0007">7, 13, 14</a>] With 24-week treatment, lower response rates were observed in genotype 3–infected patients who were treatment experienced (77%), particularly those with cirrhosis (60%), compared with those who were treatment naïve (93%).[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0007">7, 15</a>] In addition, there was an increased incidence of anemia, which is consistent with the hemolytic anemia known to occur with RBV treatment.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0015">15, 16</a>] Thus, patients with genotype 3 infection have a need for improved treatment options, preferably with therapies of shorter duration and without the addition of Peg-IFN or RBV.</p> <p>DCV was evaluated in combination with SOF in a phase II study.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0017">17</a>] Treatment for 24 weeks with DCV plus SOF, with or without the addition of RBV, resulted in an 89% rate of sustained virological response (SVR) at post-treatment week 12 (SVR12) among 18 treatment-naïve patients with genotype 3 infection.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0011">11, 17</a>] Of 5 genotype 3–infected patients who had ≥F3 fibrosis (based on FibroTest scores), all 5 achieved SVR12.<sup>11</sup> In this phase III study, the efficacy and safety of 12-week, RBV-free treatment with DCV plus SOF were evaluated in treatment-naïve and treatment-experienced patients chronically infected with HCV genotype 3.</p> <p><strong>Patients and Methods</strong></p> <p><strong><em>Study Design and Patients</em></strong></p> <p>This was an open-label, two-cohort phase III study (<a href="http://clinicaltrials.gov/">ClinicalTrials.gov</a>: NCT02032901) of a 12-week regimen of DCV plus SOF in genotype 3 infection. Eligible patients were males and females ≥18 years of age with chronic genotype 3 infection who were either treatment naïve or treatment-experienced and had HCV-RNA levels ≥10,000 IU/mL at screening. Treatment-naïve patients had no previous exposure to any IFN formulation, RBV, or any HCV direct-acting antiviral (DAA) agent, whereas treatment-experienced patients received previous therapy with IFN-α (with or without RBV), SOF plus RBV, or other anti-HCV agents, such as inhibitors of cyclophilin or microRNA. Patients who received previous therapy with NS5A inhibitors and those who previously discontinued treatment with SOF plus RBV prematurely because of intolerance (other than exacerbation of anemia) were excluded. All permitted previous anti-HCV therapies must have been completed or discontinued at least 12 weeks before screening.</p> <p>Patients with compensated cirrhosis were eligible (up to 50% in each cohort), with cirrhosis determined by liver biopsy (Metavir F4) at any time before screening, FibroScan (>14.6 kilopascals [kPa]) within 1 year of baseline (day 1), or a FibroTest score ≥0.75 coupled with an aspartate aminotransferase (AST) to platelet ratio index (APRI) >2. Per the study protocol, FibroTest assessments (scores determined by BioPredictive) were performed during screening; a FibroTest score ≤0.74 corresponded to a fibrosis stage of F0-F3, and a score >0.74 corresponded to a fibrosis stage of F4. Key patient exclusion criteria included chronic liver disease other than that related to HCV infection, infection with HCV genotypes other than genotype 3 or with mixed genotypes, coinfection with human immunodeficiency virus (HIV) or hepatitis B virus, documented or suspected HCC, or evidence of hepatic decompensation.</p> <p>All patients received open-label treatment with DCV 60 mg plus SOF 400 mg once-daily for 12 weeks, with a subsequent 24-week follow-up. The study was conducted in accord with the ethical principles that originated in the Declaration of Helsinki, and the study protocol was approved by the institutional review board or independent ethics committee at each study site. All patients provided written informed consent before participation in the study.</p> <p><strong><em>Study Assessments</em></strong></p> <p>Adherence to study treatment was assessed at each study visit based on tablet counts and dosing information recorded in patient diaries. HCV-RNA levels were determined at baseline; on-treatment weeks 1, 2, 4, 6, 8, and 12; and post-treatment weeks 4, 12, and 24 using the COBAS TaqMan HCV test (version 2.0; Roche Molecular Systems, Pleasanton, CA), with a lower limit of quantitation (LLOQ) of 25 IU/mL. HCV genotype or subtype was determined using the RealTime HCV genotype II assay (Abbott Molecular, Abbott Park, IL) and confirmed by viral sequence analysis. <em>Interleukin-28B</em> (<em>IL28B</em>) genotype (rs12979860 single-nucleotide polymorphism) was determined by polymerase chain reaction amplification and sequencing. Resistance testing was performed by population-based sequencing of plasma samples from all patients at baseline and from patients with virological failure (VF) who had HCV-RNA levels of ≥1,000 IU/mL. VFs included virological breakthrough (VBT), defined as a confirmed, on-treatment HCV-RNA increase of ≥1 log<sub>10</sub> IU/mL from nadir or a confirmed HCV-RNA measurement of ≥LLOQ following a previous measurement of <LLOQ; relapse, defined as a confirmed HCV-RNA measurement of ≥LLOQ post-treatment following an undetectable HCV-RNA measurement at the end of treatment; and HCV-RNA measurement of ≥LLOQ at any time point not meeting the definition of VBT or relapse. Safety and tolerability were assessed based on adverse event (AE) reporting, clinical laboratory tests, vital signs, and physical examinations.</p> <p><strong><em>Statistical Analyses</em></strong></p> <p>The coprimary endpoints were the proportions of treatment-naïve and treatment-experienced patients achieving SVR12 (defined as HCV-RNA levels <LLOQ, either detectable or undetectable). Target sample sizes of 100 treatment-naïve and 50 treatment-experienced patients would provide 95% confidence intervals (CI) for the observed SVR12 rates of within 9.7% and 14.2%, respectively, when the observed SVR12 rates were ≥75%. In the treatment-naïve cohort, a target sample size of 100 patients would provide a 95% CI lower bound of >76% with an observed SVR12 rate of 85%. In the treatment-experienced cohort, a target sample size of 50 patients would provide a 95% CI lower bound of >73% with an observed SVR12 rate of 86%.</p> <p>Secondary efficacy endpoints included the proportion of patients achieving HCV-RNA levels <LLOQ, detectable or undetectable, at on-treatment weeks 1, 2, 4, 6, and 8, the end of treatment, and post-treatment weeks 4 and 24; the proportion achieving HCV-RNA levels <LLOQ, undetectable, at on-treatment weeks 1, 2, 4, 6, and 8 and the end of treatment; and SVR12 rates by baseline cirrhosis status and <em>IL28B</em> genotype. Efficacy analyses included all patients who received ≥1 dose of study medications, and response rates and two-sided 95% exact binomial CI were estimated by cohort for efficacy endpoints.</p> <p><strong>Results</strong></p> <p><strong><em>Patients</em></strong></p> <p>A total of 152 patients received ≥1 dose of study medications; of these, 101 (66%) were treatment naïve and 51 (34%) were treatment experienced. Treatment-experienced patients included those who had previously failed treatment with IFN-based therapies or other anti-HCV therapies, including SOF- and alisporivir (ALV)-containing regimens (Table <a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-tbl-0001">1</a>). One hundred (99%) treatment-naïve patients and all 51 (100%) treatment-experienced patients completed 12 weeks of treatment; 1 treatment-naïve patient discontinued treatment after week 8 because of pregnancy, but achieved SVR12.</p> <p><font face="Thread-000018c0-Id-00000009"><font size="2"><font color="#cccccc"><span class="table__caption-label" style="vertical-align: baseline; background-position: 0px 0px; line-height: 1.4"><strong>Table 1. </strong></span><em>Demographic and Baseline Disease Characteristics</em></font></font></font></header> </p> <p><a href="http://lh3.googleusercontent.com/-Pb5MTBJ8Zd0/VTkVTlpD8xI/AAAAAAAANLs/3fMYm2Xn5yQ/s1600-h/Capture%25255B5%25255D.png"><img title="Capture" style="border-left-width: 0px; border-right-width: 0px; background-image: none; border-bottom-width: 0px; padding-top: 0px; padding-left: 0px; display: inline; padding-right: 0px; border-top-width: 0px" border="0" alt="Capture" src="http://lh3.googleusercontent.com/-O5FqcNBBBXk/VTkVUFCX4jI/AAAAAAAANL0/Ews2n6kAil8/Capture_thumb%25255B3%25255D.png?imgmax=800" width="442" height="405" /></a></p> <p><a href="http://lh3.googleusercontent.com/-iPPI8PSAzLc/VTkVUxJV0OI/AAAAAAAANL8/dgRla9m_YXI/s1600-h/Capture2%25255B5%25255D.png"><img title="Capture2" style="border-left-width: 0px; border-right-width: 0px; background-image: none; border-bottom-width: 0px; padding-top: 0px; padding-left: 0px; display: inline; padding-right: 0px; border-top-width: 0px" border="0" alt="Capture2" src="http://lh3.googleusercontent.com/-mojZZXayoEA/VTkVVTO8vMI/AAAAAAAANME/mgVvjZoEbxI/Capture2_thumb%25255B3%25255D.png?imgmax=800" width="442" height="405" /></a></p> <p><a href="http://lh3.googleusercontent.com/-NBw2ZosBLCs/VTkVV_s2DiI/AAAAAAAANMM/s83Gm0ElSkk/s1600-h/Capture3%25255B4%25255D.png"><img title="Capture3" style="border-left-width: 0px; border-right-width: 0px; background-image: none; border-bottom-width: 0px; padding-top: 0px; padding-left: 0px; display: inline; padding-right: 0px; border-top-width: 0px" border="0" alt="Capture3" src="http://lh3.googleusercontent.com/-ujB6OjNfebo/VTkVWgJ4SyI/AAAAAAAANMQ/ZZrzQ9-n6HA/Capture3_thumb%25255B2%25255D.png?imgmax=800" width="442" height="304" /></a></p> <p>Overall, patients were 90% white and 59% male, with a median age of 55 years; the majority of patients had baseline HCV-RNA levels of ≥800,000 IU/mL (71%) and a non-CC <em>IL28B</em> genotype (61%; Table <a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-tbl-0001">1</a>). All patients were chronically infected with HCV genotype 3. Cirrhosis, as determined by liver biopsy, FibroScan, or FibroTest/APRI per protocol, was present in 21% of patients overall (treatment naïve, 19%; treatment experienced, 25%). Fibrosis stage was also determined using FibroTest scores, based on which, 119 (78%) patients had a fibrosis stage of F0-F3 and 30 (20%) had a fibrosis stage of F4; FibroTest scores were not reported for 3 patients (all 3 achieved SVR12). Baseline albumin levels were similar in patients with cirrhosis (median, 41 g/L; range, 33-47) and without cirrhosis (median, 44 g/L; range, 36-53); baseline platelet (PLT) counts were lower in patients with cirrhosis (median, 124.5 × 10<sup>9</sup>/L; range, 62-382) than in those without cirrhosis (median, 200 × 10<sup>9</sup>/L; range, 89-334).</p> <p><strong><em>Virological Response</em></strong></p> <p>DCV plus SOF for 12 weeks achieved SVR12 rates of 90% in treatment-naïve patients and 86% in treatment-experienced patients with genotype 3 infection, with an overall SVR12 rate of 89% (Table <a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-tbl-0002">2</a>). Rapid and sustained reductions from baseline in HCV-RNA levels were observed, with mean decreases of 4.3-4.5 log<sub>10</sub> IU/mL at on-treatment week 1 and 4.7-4.9 log<sub>10</sub> IU/mL at on-treatment week 2. The proportion of patients achieving HCV-RNA levels <LLOQ, detectable or undetectable, at early on-treatment time points in the treatment-naïve and treatment-experienced cohorts, respectively, was 40% and 24% for week 1, 77% and 69% for week 2, and 94% and 98% for week 4. HCV-RNA levels were undetectable at end of treatment in ≥99% of patients.</p> <p><strong>Table 2.</strong> <em>Virological Response</em></p> <p><a href="http://lh3.googleusercontent.com/-pidsA0_W1BY/VTkVW7mtTyI/AAAAAAAANMY/-l4PqdEwxDY/s1600-h/Capture%25255B10%25255D.png"><img title="Capture" style="border-left-width: 0px; border-right-width: 0px; background-image: none; border-bottom-width: 0px; padding-top: 0px; padding-left: 0px; display: inline; padding-right: 0px; border-top-width: 0px" border="0" alt="Capture" src="http://lh3.googleusercontent.com/-EnRs041V74U/VTkVXUMIiZI/AAAAAAAANMg/VLAkJvtwYjs/Capture_thumb%25255B6%25255D.png?imgmax=800" width="442" height="336" /></a></p> <p><a href="http://lh3.googleusercontent.com/-E5ehsNbp6Pc/VTkVX7jFRJI/AAAAAAAANMs/eYttj3VpA6k/s1600-h/Capture2%25255B10%25255D.png"><img title="Capture2" style="border-left-width: 0px; border-right-width: 0px; background-image: none; border-bottom-width: 0px; padding-top: 0px; padding-left: 0px; display: inline; padding-right: 0px; border-top-width: 0px" border="0" alt="Capture2" src="http://lh3.googleusercontent.com/-_2kDF_JRgJI/VTkVYemQ42I/AAAAAAAANMw/n64ZCBFbshM/Capture2_thumb%25255B6%25255D.png?imgmax=800" width="442" height="361" /></a></p> <p>The relationship between virological response (VR) at early on-treatment time points and achievement of SVR12 was assessed. SVR12 was achieved by 94% of patients with HCV-RNA levels <LLOQ, detectable or undetectable, and 86% of patients with HCV-RNA levels ≥LLOQ, at week 1; 92% and 79% of patients with HCV-RNA levels <LLOQ, detectable or undetectable, or ≥LLOQ, respectively, at week 2 achieved SVR12. Among patients with HCV-RNA levels <LLOQ, detectable or undetectable, at week 4, 90% achieved SVR12, compared with 71% of patients with HCV-RNA levels ≥LLOQ. When VR at week 4 was assessed based on undetectable HCV-RNA levels, the proportion of patients with a week 4 response who achieved SVR12 was 91%.</p> <p>Analysis of SVR12 in patient subgroups based on baseline characteristics showed no notable differences by gender, age, HCV-RNA levels, or <em>IL28B</em> genotype (Fig. <a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-fig-0001">1</a>). Among treatment-experienced patients, SVR12 was achieved by 25 of 31 patients with previous relapse and by all 7 null responders, 2 partial responders, and 2 patients who experienced VBT with past treatment. In addition, all 6 patients who were intolerant of past treatment achieved SVR12, as did 2 of 3 patients with other types of past treatment failure (HCV-RNA never undetectable on treatment or indeterminate). SVR12 was achieved in 5 of 7 patients who previously failed treatment with an SOF-containing regimen and in both patients who previously failed treatment with an ALV-containing regimen.</p> <p><a href="http://lh3.googleusercontent.com/-H-RljPr1NGQ/VTkVY4ztpiI/AAAAAAAANM8/6Pe_owexD4c/s1600-h/hep27726-fig-0001%25255B4%25255D.png"><img title="hep27726-fig-0001" style="border-left-width: 0px; border-right-width: 0px; background-image: none; border-bottom-width: 0px; padding-top: 0px; padding-left: 0px; display: inline; padding-right: 0px; border-top-width: 0px" border="0" alt="hep27726-fig-0001" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhsUmbXrUYg_mbvwoUgd5v5MCBgfqk-fWr3TwdEMId1XxI0HCbiGjKqfdGrlZlTMsbV_7e2YiwG6hUPuI1y1iMZd86CirPpUq2sqxfoF6AiwnpuZD__rBPBO0Bva54qHukls3CH1w_LXQ/?imgmax=800" width="442" height="198" /></a></p> <p><strong>Figure 1.</strong> <em>VR by baseline characteristics. <sup>a</sup>HCV RNA <LLOQ (25 IU/mL), detectable or undetectable; error bars reflect 95% CI.</em></p> <p>SVR12 rates were higher in patients without cirrhosis (96%) than in patients with cirrhosis (63%; Fig. <a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-fig-0002">2</a>A), although high response rates at end of treatment were noted both in patients with and without cirrhosis (97% and 100%, respectively). A similar trend was observed when SVR12 was analyzed by fibrosis stage, based on FibroTest scores, of F0-F3 (93%) and F4 (70%; Fig. <a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-fig-0002">2</a>B). Overall, results by cirrhosis status or by fibrosis stage based on FibroTest scores were generally consistent between the treatment-naïve and treatment-experienced cohorts. VR at early on-treatment time points did not appear to impact SVR12 rates in patients with cirrhosis, given that the proportion of patients with cirrhosis who achieved SVR12 was the same among those who did or did not have undetectable HCV-RNA levels at on-treatment week 4 (10 of 16 patients with undetectable HCV-RNA levels at week 4 and 10 of 16 patients without undetectable HCV-RNA levels at week 4 achieved SVR12).</p> <p><strong><a href="http://lh3.googleusercontent.com/-EYSU0zIQ5mE/VTkVZ74h7BI/AAAAAAAANNM/rXguu7DBOSI/s1600-h/hep27726-fig-0002%25255B4%25255D.png"><img title="hep27726-fig-0002" style="border-left-width: 0px; border-right-width: 0px; background-image: none; border-bottom-width: 0px; padding-top: 0px; padding-left: 0px; display: inline; padding-right: 0px; border-top-width: 0px" border="0" alt="hep27726-fig-0002" src="http://lh3.googleusercontent.com/-5EMGFg7JH9g/VTkVaRMMeDI/AAAAAAAANNQ/MezOucSGLPU/hep27726-fig-0002_thumb%25255B2%25255D.png?imgmax=800" width="442" height="427" /></a></strong></p> <p><strong>Figure 2.</strong> <em>VR in patients with (A) cirrhosis or (B) fibrosis stage of F4 (FibroTest). <sup>a</sup>HCV RNA <LLOQ (25 IU/mL), detectable or undetectable; error bars reflect 95% CI. <sup>b</sup>Among 32 patients with cirrhosis, 11 (34%) had baseline PLT counts ≤100 × 10<sup>9</sup> cells/mL. <sup>c</sup>Cirrhosis status determined in 141 patients by liver biopsy (Metavir F4), FibroScan (>14.6 kPa), or FibroTest score ≥0.75 and APRI >2; for 11 patients, cirrhosis status was missing or inconclusive (FibroTest score >0.48 to <0.75 or APRI >1 to ≤2). <sup>d</sup>Per the study protocol, FibroTest assessments were performed during screening (FibroTest scores not available for 3 treatment-naïve patients); F0-F3 defined as FibroTest score of ≤0.74 and F4 defined as FibroTest score of >0.74.</em></p> <p>The relationship between resistance-associated variants (RAVs) at NS5A amino acid positions M28, A30, L31, and Y93 at baseline and SVR12 was assessed. No patients had L31 polymorphisms at baseline; 1 patient without cirrhosis had M28V at baseline and achieved SVR12. NS5A-A30 polymorphisms were detected in 14 of 147 patients at baseline. Of the 14 patients with A30 polymorphisms, 9 of 9 without cirrhosis and 1 of 5 with cirrhosis achieved SVR12. Among the 4 patients with cirrhosis with baseline A30 polymorphisms who did not achieve SVR12, 2 also had Y93H at baseline, 1 had A30T, which has no effect on DCV potency <em>in vitro</em>, and 1 had A30K, which was associated with SVR12 in the 5 remaining patients with this polymorphism.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0018">18</a>] NS5A-Y93H was detected in 13 of 147 patients who had NS5A sequence at baseline; of these 13 patients, 6 of 9 without cirrhosis and 1 of 4 with cirrhosis achieved SVR12. No NS5B RAVs were detected at amino acid positions associated with resistance to SOF (159, 282, or 321) at baseline.</p> <p><strong><em>Virologic Failure</em></strong></p> <p>Occurrence of VF was low, with no VBTs observed (Table <a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-tbl-0002">2</a>). One treatment-naïve patient with cirrhosis had a quantifiable HCV-RNA level of 53 IU/mL at end of treatment; this event did not meet the protocol definition of VBT, which required on-treatment confirmation of the HCV-RNA measurement. The patient was a slow responder through week 4 and had a low baseline PLT count (83 × 10<sup>9</sup> cells/L), reflecting advanced cirrhosis. Sixteen patients (9 treatment naïve and 7 treatment experienced) had post-treatment relapse, of whom 11 (7 treatment naïve and 4 treatment experienced) had cirrhosis at baseline. All of the relapses occurred by post-treatment week 4 except for 1, which occurred between post-treatment week 4 and post-treatment week 12 in a treatment-naïve patient without cirrhosis. Factors that may have contributed to treatment failure in this patient included a very high baseline HCV-RNA level (27.5 × 10<sup>6</sup> IU/mL), presence of the NS5A-Y93H RAV at baseline, and incomplete treatment adherence (93% adherent), although no relapses occurred among the other 4 patients who were not completely adherent to treatment (3 with 90%-95% adherence and 1, who discontinued after week 8 because of pregnancy, with 66% adherence). The NS5A-Y93H RAV emerged in 9 of 16 patients with relapse; of the remaining 7 patients with relapse, 6 had NS5A-Y93H at baseline and 1 had emergent NS5A-L31I. NS5B RAVs at amino acid positions associated with resistance to SOF (159, 282, or 321) were not detected at relapse.</p> <p><strong><em>Safety and Tolerability</em></strong></p> <p>DCV plus SOF was well tolerated, with no AEs leading to discontinuation of treatment (Table <a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-tbl-0003">3</a>). There were no deaths and only 1 serious AE (SAE) was reported on-treatment: an event of gastrointestinal hemorrhage that was considered not related to study medications. The most common AEs (in >10% of patients) were headache, fatigue, and nausea, and the incidence of grade 3 AEs was low (2%), with no grade 4 AEs reported.</p> <p><strong>Table 3.</strong> <em>Safety and Tolerability</em></p> <p><a href="http://lh3.googleusercontent.com/-giCd-mejPsM/VTkVaqbbQ4I/AAAAAAAANNY/A-2O-w2CR0A/s1600-h/Capture%25255B15%25255D.png"><img title="Capture" style="border-left-width: 0px; border-right-width: 0px; background-image: none; border-bottom-width: 0px; padding-top: 0px; padding-left: 0px; display: inline; padding-right: 0px; border-top-width: 0px" border="0" alt="Capture" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjBtIS_lqjU_HURFYBfDbo51BARRPoX95QFTCB3jHztN4ysPtiD0jdaeIHuMTmPor-Fsp-VwDfjmSV2rjkkSp4WZfPTbDFSBh556mLzdgec9bqvDo5_8FZxqfSK3NQH-aCENezJs7SuoA/?imgmax=800" width="442" height="336" /></a></p> <a href="http://lh3.googleusercontent.com/-H8bBPvjTsjg/VTkVbaS7ctI/AAAAAAAANNo/lNUZxMud1WI/s1600-h/Capture2%25255B15%25255D.png"><img title="Capture2" style="border-left-width: 0px; border-right-width: 0px; background-image: none; border-bottom-width: 0px; padding-top: 0px; padding-left: 0px; display: inline; padding-right: 0px; border-top-width: 0px" border="0" alt="Capture2" src="http://lh3.googleusercontent.com/-fn80fJaRm4c/VTkVbwiQrbI/AAAAAAAANNw/QtXC-31tDJw/Capture2_thumb%25255B9%25255D.png?imgmax=800" width="442" height="372" /></a> <p><a href="http://lh3.googleusercontent.com/-lI8XkF1zQqE/VTkVcQ_mNmI/AAAAAAAANN8/0CH7f8JTPlw/s1600-h/Capture3%25255B9%25255D.png"><img title="Capture3" style="border-left-width: 0px; border-right-width: 0px; background-image: none; border-bottom-width: 0px; padding-top: 0px; padding-left: 0px; display: inline; padding-right: 0px; border-top-width: 0px" border="0" alt="Capture3" src="http://lh3.googleusercontent.com/-uX_Dhg87Now/VTkVc6B2oPI/AAAAAAAANOA/wWcqyiXAwJ4/Capture3_thumb%25255B5%25255D.png?imgmax=800" width="442" height="84" /></a></p> <p>Few treatment-emergent grade 3/4 laboratory abnormalities were observed with DCV plus SOF, with such events reported only for absolute lymphocytes, PLTs, international normalized ratio (INR), and lipase. Incidences of these grade 3/4 laboratory abnormalities were low (≤2% each), and none led to clinically significant bleeding or pancreatitis or to treatment discontinuation. Moreover, these abnormalities were primarily transient increases or decreases that were not present for prolonged periods during treatment. No treatment-emergent grade 3/4 abnormalities were observed in hemoglobin (Hgb) or liver-related parameters, including alanine aminotransferase (ALT) and AST and total bilirubin.</p> <p><strong>Discussion</strong></p> <p>In patients chronically infected with HCV genotype 3, the all-oral, 12-week regimen of DCV plus SOF achieved SVR12 rates of 90% in treatment-naïve patients and 86% in treatment-experienced patients; SVR12 was achieved in 96% of patients without cirrhosis and in 63% of patients with cirrhosis. No VBTs were observed, and all but 1 patient achieved a VR at end of treatment. The combination of DCV plus SOF was well tolerated, with a low incidence of SAEs, no deaths or AEs leading to discontinuation, and few treatment-emergent grade 3/4 laboratory abnormalities. These results are generally consistent with those from a phase II study demonstrating the efficacy and tolerability of DCV plus SOF, with or without RBV, in patients with genotype 3 infection.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0017">17</a>] Overall, findings from the present study show that in genotype 3–infected patients without cirrhosis, a 12-week treatment with DCV plus SOF is efficacious, compared with the current 24-week, all-oral regimens containing RBV.</p> <p>SVR12 rates were comparable across subgroups based on gender, age, baseline HCV-RNA levels, and <em>IL28B</em> genotype. Notably, this study included patients who previously failed treatment with SOF- or ALV-containing regimens, of whom 71% and 100%, respectively, achieved SVR12. A limitation of the study is that the impact of race on SVR12 rates could not be fully assessed owing to the high proportion of white patents enrolled (90% overall); however, all 6 of the black patients enrolled in the study achieved SVR12.</p> <p>SVR12 rates with DCV plus SOF were higher in patients without cirrhosis than in those with cirrhosis, and in patients with a fibrosis stage (based on FibroTest scores) of F0-F3 than in those with F4. However, the 63% SVR12 rate in patients with cirrhosis is comparable to that achieved with 16 (61%) or 24 weeks (67%) of SOF plus RBV, with the advantages of an IFN-free and shorter-duration regimen.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0007">7</a>] On-treatment and end-of-treatment response rates were similar in patients with or without cirrhosis, with relapse accounting for all but one of the treatment failures: among the 16 patients with relapse, 11 had cirrhosis. Relapse was more frequent in the 4 patients with cirrhosis who had Y93H RAVs at baseline, although these RAVs did not measurably affect on-treatment response. Other possible reasons for the higher relapse rate in genotype 3–infected patients with cirrhosis remain uncertain. Given that high relapse rates have also been observed with other all-oral regimens after treatment of genotype 3 infection,[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0014">14, 18</a>] this HCV genotype may be more difficult than others to eradicate with DAAs, particularly in patients with cirrhosis. Multiple factors may contribute to this effect and require further study.</p> <p>The robust on-treatment VR with DCV plus SOF, with nearly all VFs the result of post-treatment relapse, suggests that optimizing treatment outcomes in patients with cirrhosis could include the addition of RBV or a longer treatment duration. A randomized study has been initiated (<a href="http://clinicaltrials.gov/">clinicaltrials.gov</a>: NCT02319031)[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0019">19</a>] in which patients with genotype 3 infection and compensated advanced cirrhosis are receiving DCV in combination with SOF and RBV for 12 or 16 weeks, with the objective of determining whether adding RBV and extending treatment will improve the durability of response post-treatment. This strategy has been successful with other all-oral regimens. A recent report regarding a phase II study of SOF plus GS-5816, with or without RBV, suggests that the addition of RBV improves response rates in genotype 3–infected patients with cirrhosis. In treatment-experienced patients with cirrhosis treated for 12 weeks, SVR12 rates were higher with SOF plus GS-5816 with the addition of RBV (85%-96%) than with sofosbuvir plus GS-5816 alone (58%-88%).[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0020">20</a>] The combination of LDV plus SOF with RBV for 12 weeks has been reported to provide SVR12 rates of 89% in genotype 3–infected, treatment-experienced patients without cirrhosis and a lower rate of 77% in those with cirrhosis.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0021">21</a>] Because DCV has shown greater potency <em>in vitro</em> against genotype 3, compared with LDV,[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0011">11, 22-24</a>] the combination of DCV plus SOF, with the addition of RBV, may be expected to provide improved response rates relative to the current results in patients with cirrhosis. DCV plus SOF, with or without RBV, is also being evaluated in additional patient populations with high unmet medical needs in other studies of the ALLY phase 3 program. These include patients who have cirrhosis or who are post–liver transplant (ALLY-1; <a href="http://clinicaltrials.gov/">ClinicalTrials.gov</a>: NCT02032875) and patients who are coinfected with HIV (ALLY-2; <a href="http://clinicaltrials.gov/">ClinicalTrials.gov</a>: NCT02032888). DCV has been approved in combination with other anti-HCV agents in Europe and Japan.</p> <p>DCV plus SOF was associated with a favorable safety profile. Incidences of SAEs and grade 3/4 AEs were low, and no deaths or AEs leading to discontinuation were reported. Few grade 3/4 laboratory abnormalities were reported, and the events that were observed were primarily transient changes and did not lead to treatment discontinuation. No grade 3/4 abnormalities in Hgb emerged during treatment, whereas previous studies have reported reductions in Hgb levels with the combination of SOF plus RBV.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0014">14, 15</a>] Overall, no notable safety concerns were observed with the combination of DCV plus SOF.</p> <p>In summary, a 12-week regimen of DCV plus SOF achieved SVR12 in 96% of treatment-naïve and treatment-experienced patients with genotype 3 infection without cirrhosis and was well tolerated. This regimen, without the addition of RBV and with a shorter treatment duration relative to currently approved all-oral regimens, demonstrated high SVR12 rates across patient subgroups, except in patients with cirrhosis and regardless of past treatment response. These findings support the 12-week regimen of DCV plus SOF as an efficacious, well-tolerated treatment option. Additional evaluation to optimize efficacy in genotype 3–infected patients with cirrhosis is underway.[<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#hep27726-bib-0019">19</a>]</p> <p><a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259#references-section" target="_blank"><strong>References</strong></a></p> <p><a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/hep.27726/?campaign=wlytk-42068.5028009259" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-74058270013834228192015-04-23T10:21:00.001-04:002015-04-23T10:21:08.617-04:00FDA to revisit its policies on homeopathic products<p>Provided by <a href="http://www.washingtonpost.com/" target="_blank">The Washington Post</a></p> <p align="center"><a href="http://lh3.googleusercontent.com/-d817YQJYgRg/VTj_0Y17FeI/AAAAAAAANLU/upo04ufZyjo/s1600-h/iStock_000029270656_Large1426147381%25255B3%25255D.jpg"><img title="iStock_000029270656_Large1426147381" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="iStock_000029270656_Large1426147381" src="http://lh3.googleusercontent.com/-b0EKhnNpcJ8/VTj_05yneuI/AAAAAAAANLY/yBK7HsIGXqw/iStock_000029270656_Large1426147381_thumb%25255B1%25255D.jpg?imgmax=800" width="242" height="161" /></a></p> <p align="center"><em>Homeopathic remedies, derived from plants, minerals and other substances, often are tailored to individual patients. (iStock)</em></p> <p>By <a href="http://www.washingtonpost.com/people/brady-dennis">Brady Dennis</a> April 18</p> <p>Homeopathy has long been a magnet for controversy, earning a devoted following among patients who insist its remedies are safe and effective, while attracting criticism from many doctors and researchers who say its treatments offer no more help than a placebo.</p> <p>After problems within the industry in recent years, the Food and Drug Administration says it wants to revisit how it oversees homeopathic products, which can be manufactured and marketed without prior approval from regulators.</p> <p>Should the FDA regulate homeopathic remedies such as Cold-Eeze the same way it does over-the-counter drugs such as Advil? Should it hold products such as Zicam, which contains small amounts of zinc, to the same safety and efficacy standards that it requires for Tylenol?</p> <p>Hundreds of public <a href="http://www.regulations.gov/#!docketDetail;D=FDA-2015-N-0540">comments have poured in to the FDA</a> ahead of two days of hearings that begin Monday. The agency said it wants more data to “better assess the risks and benefits” of homeopathic remedies, which have become a mainstay on modern pharmacy shelves, often sold alongside over-the-counter pharmaceutical drugs. Stores such as Whole Foods feature sections of homeopathic remedies aimed at treating conditions including allergies and heartburn.</p> <p>The FDA has not made any decisions about whether to change how it approaches homeopathic products, said Cynthia Schnedar, director of the Office of Compliance at the FDA’s Center for Drug Evaluation and Research. “At this stage,” she said, “we are gathering information about whether to adjust our current enforcement policy.”</p> <p>The FDA has issued nearly 40 warning letters since 2009 to companies making homeopathic products, Schnedar said.</p> <p>Last month, the agency warned consumers not to rely on over-the-counter asthma products labeled as homeopathic, saying they have not been evaluated for safety and effectiveness. In 2009, the FDA warned consumers to stop using several types of Zicam cold remedies after reports of more than 130 cases of people losing their sense of smell; the company <a href="http://www.zicam.com/our-story.php">issued</a> a recall. The following year, Hyland’s Teething Tablets were recalled after <a href="http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm230764.htm">reports</a> of reactions in some children; the tablets later were <a href="http://www.hylands.com/news/hylands-teething-recall.php">reintroduced</a> with a new formulation.</p> <p>Homeopathic medicines have had the <a href="http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074360.htm">same legal status</a> as regular pharmaceuticals since 1938, when then-New York Sen. Royal Copeland, who was a trained homeopath, helped shepherd a landmark food and drug law through Congress.</p> <p>In the 1970s, lawmakers directed the FDA to review the safety and effectiveness of over-the-counter medications. But the agency deferred reviewing homeopathic treatments at the time and <a href="https://www.federalregister.gov/articles/2015/03/27/2015-07018/homeopathic-product-regulation-evaluating-the-food-and-drug-administrations-regulatory-framework">last evaluated</a> its policies in 1988. It has allowed most prescription and non-prescription homeopathic products to go to market without prior approval.</p> <p>Homeopathy traces its founding back two centuries to German doctor and chemist Samuel Hahnemann — whose <a href="http://www.nlm.nih.gov/hmd/medtour/hahnemann.html">statue</a>, incidentally, has been in downtown Washington, east of Scott Circle, since 1900.</p> <p>A key principle underpinning the practice of homeopathy is the notion that “like cures like,” or that substances that create certain symptoms in a healthy person can help to cure diseases with similar symptoms. Homeopathic remedies, derived from plants, minerals and other substances, often are tailored to individual patients. Many treatments are diluted to the point that there is little or no active ingredient remaining. The dilution, which homeopaths believe triggers an immune response in the body, has led skeptics to claim that the practice amounts to little more than selling water and wishful thinking.</p> <p>The National Institutes of Health has said that there is “little evidence to support homeopathy as an effective treatment for any specific condition,” and that “several key concepts of homeopathy are inconsistent with fundamental concepts of chemistry and physics.”</p> <p>Last month, Australia’s National Health and Medical Research Council concluded that “there are no health conditions for which there is reliable evidence that homeopathy is effective.” The organization found that there were “no good-quality, well-designed studies with enough participants” to determine whether such treatments were more effective than a placebo.</p> <p>Edzard Ernst, an emeritus professor at the University of Exeter in England and an outspoken homeopathy critic, said in an e-mail, “There is an appalling amount of misinformation out there, targeted at the often naive consumer.”</p> <p>He said that the FDA should require homeopathic products to meet the same standards as other medications. “This is a most dangerous situation, and has to be corrected in the interest of public safety,” he said.</p> <p>Given such criticisms, the FDA’s decision to revisit the issue has worried advocates of homeopathy, who fear that any broad new regulations might unfairly cripple the industry.</p> <p>“Obviously, people are alarmed and wondering what the FDA is up to,” said Jennifer Jacobs, who practiced homeopathy for 30 years and is now a clinical assistant professor of epidemiology at the University of Washington School of Public Health. “It seems to me that they have bigger fish to fry.”</p> <p>Jacobs said that homeopathic remedies have a long history of overall safety, particularly when compared with the harmful side effects caused by many conventional drugs. In addition, she said, homeopathic remedies shouldn’t be dismissed merely because science lacks a clear explanation for why they have helped patients.</p> <p>“It’s foolish to think we understand everything about physics and chemistry at this point in time,” Jacobs said. “Just because we don’t understand exactly how they work doesn’t mean we won’t be able to in the future.”</p> <p>Ronald Whitmont, a homeopathic doctor in New York and president of the American Institute of Homeopathy, said his organization supports the FDA’s actions to crack down on poor manufacturing practices. “There are always bad apples in the manufacturing world, and they need to be policed just like in any other industry,” he said. “We are behind the FDA. Their concern is our concern.”</p> <p>But he said he hopes the hearing doesn’t turn into a debate about the legitimacy of homeopathy itself, which has a long safety record and a growing list of ardent patients nearly two centuries after it began.</p> <p>“Since homeopathy has been in existence, there have been detractors who said this couldn’t possibly work,” Whitmont said. “If it doesn’t work, why is it used worldwide by millions of people? Why isn’t it going away?”</p> <p><em>Brady Dennis is a national reporter for The Washington Post, focusing on food and drug issues.</em></p> <p><a href="http://www.washingtonpost.com/national/health-science/for-first-time-in-decades-fda-to-revisit-how-it-regulates-homeopathic-products/2015/04/18/2753315c-e207-11e4-81ea-0649268f729e_story.html" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-34545002730342257602015-04-23T09:43:00.001-04:002015-04-23T09:43:11.851-04:00Positive preclinical antiviral and safety profile of MIV-802 supports continued development<p><a href="http://lh3.googleusercontent.com/-jfzVLsznqlA/VTj27OW9F6I/AAAAAAAANK8/v7Op-TnCq5Q/s1600-h/Medivir_logo%25255B44%25255D.jpg"><img title="Medivir_final_C300" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="Medivir_final_C300" src="http://lh3.googleusercontent.com/-4UAPLhWq1cg/VTj27pe4HwI/AAAAAAAANLE/I7F4XbiJj-I/Medivir_logo_thumb%25255B42%25255D.jpg?imgmax=800" width="191" height="66" /></a></p> <p><strong>Stockholm, Sweden — Medivir AB (Nasdaq Stockholm: MVIR</strong>)<strong> </strong>today announce that the preclinical antiviral and safety profile of MIV-802, Medivir’s wholly-owned nucleotide polymerase inhibitor under development for the treatment of hepatitis C virus (HCV) infection, was presented at The International Liver Congress™ 2015 of the European Association for the Study of the Liver (EASL), taking place in Vienna from April 22-26.</p> <p>The presentation, entitled “Preclinical characterization of MIV-802, a novel uridine nucleotide HCV NS5B polymerase inhibitor, for treatment of hepatitis C virus infection” (Abstract P0688), outlines the favourable preclinical profile of MIV-802. This includes selective inhibition of the HCV NS5B polymerase by the active metabolite of MIV-802 when compared with several human DNA and RNA polymerases, the potent and selective pan-genotypic inhibition of HCV RNA replication by MIV-802 <em>in vitro</em>, and its low toxicity in a range of <em>in vitro</em> and <em>in vivo</em> studies. The presentation also describes preclinical studies that show the selective delivery of high levels of the active metabolite of MIV-802 to the liver. The data therefore support the continuing development of MIV-802 for the future treatment of HCV infection in combination with other Direct Acting Antivirals (DAAs).</p> <p>Full session details and data presentation on <a href="http://www.medivir.com/">www.medivir.com</a> and listings for The International Liver Congress™ 2015 can be found at <a href="http://www.ilc-congress.eu/">http://www.ilc-congress.eu</a>.</p> <p><strong>For further information, please contact:</strong> <br />Ola Burmark, CFO Medivir AB, mobile: +46 (0)725-480 580. <br />Richard Bethell, EVP Research and Discovery, mobile: +46 (0)72-704 32 11</p> <p>Medivir is required under the Securities Markets Act to make the information in this press release public. <br />The information was submitted for publication at 14.00 CET on 23 April 2015.</p> <p><strong>About MIV-802</strong> <br />MIV-802 is a highly potent, pangenotypic nucleotide-based inhibitor of the HCV NS5B polymerase, which recently entered preclinical development. Hepatitis C treatment comprises a combination of several pharmaceuticals with different mechanisms. Nucleotides are regarded as the most important component of any such combination, due to their potent and broad spectrum antiviral effect on multiple HCV genotypes and high barriers to the emergence of resistance. Preclinical data indicate that MIV-802 can be used effectively in combination with other classes of antiviral agents for the treatment of HCV, including protease inhibitors and NS5A inhibitors.</p> <p><strong>About Medivir</strong> <br />Medivir is a research based pharmaceutical company with a research focus on infectious diseases and oncology. We have a leading competence within protease inhibitor design and nucleotide/nucleoside science and we are dedicated to develop innovative pharmaceuticals that meet great unmet medical need. Our commercial organization provides a growing portfolio of specialty care pharmaceuticals on the Nordic market. Medivir is listed on the Nasdaq Stockholm Mid Cap List.</p> <p><a href="http://www.medivir.se/v5/en/uptodate/pressrelease.cfm" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-21417652027848693272015-04-23T09:38:00.001-04:002015-04-23T09:38:16.611-04:00Enanta Announces U.S. FDA Grants Priority Review for AbbVie’s Investigational, All-Oral, Interferon-Free Treatment Regimen for Genotype 4 Chronic Hepatitis C Infection<p><a href="http://lh3.googleusercontent.com/-LnfP92mj-Xs/VTj1xFMl2HI/AAAAAAAANKs/lLBFKjV_jUA/s1600-h/bwlogo_web%25255B42%25255D.jpg"><img title="bwlogo_web" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="bwlogo_web" src="http://lh3.googleusercontent.com/-89PdaTFRJvY/VTj1xsx5h3I/AAAAAAAANK0/TflrflhMmsY/bwlogo_web_thumb%25255B40%25255D.jpg?imgmax=800" width="212" height="85" /></a></p> <p>April 23, 2015 08:16 AM Eastern Daylight Time</p> <p>WATERTOWN, Mass.--(<a href="http://www.businesswire.com/">BUSINESS WIRE</a>)--Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a research and development-focused biotechnology company dedicated to creating small molecule drugs for viral infections and liver diseases, announced today that AbbVie has stated that the U.S. Food and Drug Administration (FDA) has accepted AbbVie’s New Drug Application (NDA) and granted priority review for its all-oral, interferon-free, two direct-acting antiviral (2-DAA) treatment regimen consisting of the fixed-dose combination of ombitasvir, paritaprevir, ritonavir (OBV/PTV/r), with ribavirin (RBV) for the treatment of adult patients with chronic genotype 4 (GT4) hepatitis C virus (HCV) infection. </p> <p>The FDA grants priority review designation to investigational therapies that treat a serious condition and, if approved, would provide a significant improvement in safety or effectiveness. AbbVie’s regimen was also granted a Breakthrough Therapy designation by the FDA on June 30, 2014, a status given to investigational treatments for serious or life-threatening conditions with preliminary clinical evidence that may demonstrate substantial improvement on at least one clinically significant endpoint compared to available therapy.<sup>1</sup></p> <p>Paritaprevir is Enanta’s lead protease inhibitor identified within the ongoing Enanta-AbbVie collaboration and is one of the two DAAs in AbbVie’s treatment regimen included in the NDA for the treatment of GT4 chronic hepatitis C patients. AbbVie is responsible for all development and commercialization activities for regimens that contain paritaprevir. Paritaprevir is included in AbbVie’s GT1 HCV treatment regimens approved in the U.S. in late 2014 and in the E.U. in early 2015. In addition, Enanta will be eligible to receive annually tiered royalties ranging from the low double digits up to twenty percent, on 45% of AbbVie’s worldwide net sales of any 2-DAA paritaprevir-containing regimen. </p> <p>The Centers for Disease Control and Prevention (CDC) estimates that in the United States, 3.2 million people are chronically infected with HCV.<sup>2 </sup>While genotype 1 (GT1) is the most prevalent form of HCV in the U.S., accounting for approximately 73 percent of all cases, GT4 infection accounts for up to 6 percent of HCV infections in the U.S.<sup>3,4</sup> Hepatitis C is inflammation of the liver caused by an infection with the HCV virus.<sup>5</sup> It is transmitted when an infected person's blood enters the bloodstream of another person.<sup>6</sup> There are six major HCV genotypes (GT1-6).<sup>7</sup> Presently, there is no vaccine for HCV infection.<sup>4</sup></p> <p><b>Protease Inhibitor Collaboration with AbbVie</b> <br />In December 2006, Enanta and Abbott announced a worldwide agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors and HCV- protease-inhibitor-containing drug combinations. Paritaprevir and ABT-493 are protease inhibitors identified through the collaboration. AbbVie is Abbott’s successor under the agreement and is responsible for all development and commercialization activities for paritaprevir, as well as ABT-493, the collaboration’s next-generation protease inhibitor. </p> <p><b>About Enanta</b> <br />Enanta Pharmaceuticals is a research and development-focused biotechnology company that uses its robust chemistry-driven approach and drug discovery capabilities to create small molecule drugs for viral infections and liver diseases. Enanta is discovering, and in some cases developing, novel inhibitors designed for use against the hepatitis C virus (HCV). These inhibitors include members of the direct–acting-antiviral (DAA) inhibitor classes – protease (partnered with AbbVie), NS5A, and nucleotide polymerase – as well as a host-targeted antiviral (HTA) inhibitor class targeted against cyclophilin. In addition, Enanta has a preclinical program in non-alcoholic steatohepatitis, or NASH, which is a condition that results in liver inflammation and damage caused by a buildup of fat in the liver. </p> <p><b>Forward Looking Statements Disclaimer</b> <br />This press release contains forward-looking statements, including with respect to the prospects for AbbVie’s paritaprevir-containing regimens for patients with GT4 HCV infection. Statements that are not historical facts are based on our management’s current expectations, estimates, forecasts and projections about our business and the industry in which we operate and our management’s beliefs and assumptions. The statements contained in this release are not guarantees of future performance and involve certain risks, uncertainties and assumptions, which are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed in such forward-looking statements. Important factors that may affect actual results include the efforts of AbbVie (our collaborator on paritaprevir) regarding regulatory approval and commercialization of regimens containing paritaprevir; the level of market acceptance and the pricing and rate of reimbursement for those regimens; the impact of competitive products on the use and sales of those regimens; regulatory actions affecting clinical development of competitive product candidates; and other risk factors described or referred to in “Risk Factors” in Enanta’s most recent Form 10-K for the fiscal year ended September 30, 2014 and other periodic reports filed more recently with the Securities and Exchange Commission. Enanta cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this release, and Enanta undertakes no obligation to update or revise these statements, except as may be required by law. </p> <p><sup>1</sup> U.S. Food and Drug Administration Online. Fact Sheet: Breakthrough Therapies. <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.fda.gov%2Fregulatoryinformation%2Flegislation%2Ffederalfooddrugandcosmeticactfdcact%2Fsignificantamendmentstothefdcact%2Ffdasia%2Fucm329491.htm&esheet=51086637&newsitemid=20150423005681&lan=en-US&anchor=http%3A%2F%2Fwww.fda.gov%2Fregulatoryinformation%2Flegislation%2Ffederalfooddrugandcosmeticactfdcact%2Fsignificantamendmentstothefdcact%2Ffdasia%2Fucm329491.htm&index=1&md5=8cb673b7b50e97683c382a4f258324ce">http://www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact/significantamendmentstothefdcact/fdasia/ucm329491.htm</a>. Accessed March 20, 2015. </p> <p><sup>2</sup> Centers for Disease Control and Prevention (CDC). Hepatitis C FAQs for health professionals. <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.cdc.gov%2Fhepatitis%2Fhcv%2Fhcvfaq.htm&esheet=51086637&newsitemid=20150423005681&lan=en-US&anchor=http%3A%2F%2Fwww.cdc.gov%2Fhepatitis%2Fhcv%2Fhcvfaq.htm&index=2&md5=1c40c15b33e81e5702390ddf9de1d591">http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm</a>. Accessed March 10, 2015 </p> <p><sup>3</sup> O’Leary JG, Davis GL. Hepatitis C. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 9th ed, Vol 1. Philadelphia, PA: Saunders Elsevier. 2010:1313-1335. </p> <p><sup>4</sup> Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. <i>J Hepatology.</i> 2014;61:S45-S57. </p> <p><sup>5</sup> Mayo Clinic. Hepatitis C: Definition. <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.mayoclinic.org%2Fdiseases-conditions%2Fhepatitis-c%2Fbasics%2Fdefinition%2Fcon-20030618&esheet=51086637&newsitemid=20150423005681&lan=en-US&anchor=http%3A%2F%2Fwww.mayoclinic.org%2Fdiseases-conditions%2Fhepatitis-c%2Fbasics%2Fdefinition%2Fcon-20030618&index=3&md5=8bd995d15bd4a69076eb224850c19695">http://www.mayoclinic.org/diseases-conditions/hepatitis-c/basics/definition/con-20030618</a>. Accessed November 2013. </p> <p><sup>6</sup> World Health Organization. Hepatitis C Fact Sheet 2014. <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.who.int%2Fmediacentre%2Ffactsheets%2Ffs164%2Fen%2F&esheet=51086637&newsitemid=20150423005681&lan=en-US&anchor=http%3A%2F%2Fwww.who.int%2Fmediacentre%2Ffactsheets%2Ffs164%2Fen%2F&index=4&md5=e8dcaad99a420f65bbd066cca153ccd8">http://www.who.int/mediacentre/factsheets/fs164/en/</a>. Accessed April 2014. </p> <p><sup>7</sup> AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.hcvguidelines.org&esheet=51086637&newsitemid=20150423005681&lan=en-US&anchor=http%3A%2F%2Fwww.hcvguidelines.org&index=5&md5=740d27de671a7713745f58ab3d82b62e">http://www.hcvguidelines.org</a>. Accessed March 9, 2015. </p> <h4>Contacts</h4> <p><b>Investor</b> <br />Carol Miceli, 617-607-0710 <br />Enanta Pharmaceuticals, Inc. <br /><a href="mailto:cmiceli@enanta.com">cmiceli@enanta.com</a> <br />or <br /><b>Media</b> <br />Kari Watson, 781-235-3060 <br />MacDougall Biomedical Communications <br /><a href="mailto:kwatson@macbiocom.com">kwatson@macbiocom.com</a></p> <p><a href="http://www.businesswire.com/news/home/20150423005681/en/Enanta-Announces-U.S.-FDA-Grants-Priority-Review#.VTj1PJVFCM8" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-90719679861935669132015-04-23T01:36:00.001-04:002015-04-23T01:36:33.282-04:00Gilead’s Harvoni and Sovaldi Demonstrate Efficacy and Safety among Chronic Hepatitis C Patients with Advanced Liver Disease<p><i><b>-- High Cure Rates in More Than 600 Genotype 1 and 4 Patients With Limited or No Approved Treatment Options --</b></i></p> <p>VIENNA, Austria--(BUSINESS WIRE)--Apr. 23, 2015-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from several Phase 2 clinical studies evaluating investigational uses of Harvoni<sup>®</sup> (ledipasvir 90 mg/sofosbuvir 400 mg) and other Sovaldi<sup>®</sup> (sofosbuvir 400 mg)-based regimens for the treatment of chronic hepatitis C virus (HCV) infection in patients with advanced liver disease, including patients with decompensated cirrhosis, patients with fibrosing cholestatic hepatitis C (a rare and severe form of the disease following liver transplantation) and patients with portal hypertension. These data will be presented this week at the 50th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress™ 2015) in Vienna, Austria. </p> <p>“The patients included in these analyses are among the most difficult to both treat and cure and, until now, have had limited or no treatment options,” said Michael P. Manns, MD, Professor and Chairman, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. “These data demonstrate that, even among these difficult-to-treat patient groups, sofosbuvir-based oral therapy offers the potential of high cure rates, improves outcomes and is generally well tolerated with a favorable safety profile.” </p> <p>Harvoni and Sovaldi are each approved in the United States for the treatment of chronic HCV infection. Harvoni is indicated for patients with genotype 1; Sovaldi is used in combination with other agents and its efficacy has been established in patients with genotypes 1-4. </p> <p><b>Decompensated and Post-Liver Transplantation</b></p> <p>In SOLAR-2 (Study GS-US-337-0124, Oral #G02), 328 genotype 1 or 4 HCV patients with decompensated liver disease before liver transplantation or recurrent HCV infection following liver transplantation were randomized to receive either 12 or 24 weeks of Harvoni plus ribavirin (RBV). Ten patients were excluded from the analysis because of transplantation (n=7) or because they were pre-transplantation, but not decompensated (n=3); an additional 27 of these patients have not yet reached post-treatment week 12. The number and proportion of genotype 1 patients with available data achieving sustained virologic response 12 weeks after treatment (SVR12) are summarized in the table below. </p> <p><a href="http://lh3.googleusercontent.com/-J10CRddFuEc/VTiE3jWN8II/AAAAAAAANKQ/Se5RLW8l54E/Capture4.png?imgmax=800"><img title="Capture" style="border-left-width: 0px; border-right-width: 0px; background-image: none; border-bottom-width: 0px; padding-top: 0px; padding-left: 0px; display: inline; padding-right: 0px; border-top-width: 0px" border="0" alt="Capture" src="http://lh3.googleusercontent.com/-HC5oyUHut_Y/VTiE3xHbrNI/AAAAAAAANKY/rUF5c77cq6M/Capture_thumb2.png?imgmax=800" width="442" height="194" /></a></p> <p>Of the 32 genotype 4 patients, 27 (84 percent) achieved SVR12. Additionally, among patients with compensated and decompensated cirrhosis before and after liver transplantation, virologic response was associated with improvements in Model for End-Stage Liver Disease (MELD) and CPT scores used to stage end-stage liver disease. </p> <p>The most common adverse events were fatigue, anemia, nausea and headache. Overall, six patients discontinued treatment due to adverse events, five of whom had decompensated cirrhosis. </p> <p>Further supporting the safety profile of Harvoni plus RBV among this patient population was data from a pooled safety analysis of 659 patients treated in the SOLAR-1 and SOLAR-2 studies (ePoster #P0774). Both studies evaluated Harvoni plus RBV for 12 or 24 weeks in genotype 1 or 4 HCV patients with decompensated liver disease or recurrent HCV infection following liver transplantation. SOLAR-1 was conducted in the United States, with data presented in November at The Liver Meeting<sup> </sup>2014 and SOLAR-2 was conducted in Australia, Canada, Europe and New Zealand. Overall, adverse events were similar to those seen in previous studies, including the Phase 3 ION studies. Fewer than three percent (n=19/659) of patients discontinued due to an adverse event, none of which were attributed to Harvoni treatment. There were a total of 20 deaths in these two studies, none of which was assessed by the investigator as related to study treatment. </p> <p><b>Fibrosing Cholestatic Hepatitis C</b></p> <p>A further subset of the SOLAR-1 and SOLAR-2 studies (ePoster #P0779) demonstrated 100 percent SVR12 rates among 11 patients who were confirmed to have fibrosing cholestatic hepatitis (FCH), following 12 or 24 weeks of Harvoni plus RBV. FCH is a rare and severe form of recurrent hepatitis that occurs after liver transplantation. It is associated with high morbidity and mortality rates and there are no currently approved treatment options. </p> <p><b>Cirrhosis and Portal Hypertension</b></p> <p>Study GS-US-334-0125 (ePoster LB #4283) evaluated 50 genotype 1-4 HCV-infected patients with cirrhosis and portal hypertension. Patients were randomized to receive either 48 weeks of Sovaldi plus RBV initially (n=25) or at the conclusion of a 24-week observation period (n=21). Four patients in the observation arm discontinued the study prior to receiving treatment. Of the patients who received treatment with Sovaldi plus RBV, 72 percent (n=33/46) achieved SVR12. A subset of 37 patients had paired hepatic venous pressure gradient (HVPG) measurements at baseline and end of treatment. Of these, 38 percent (14/37) of patients experienced a ≥10 percent reduction and 24 percent (9/37) of patients experienced a ≥20 percent decrease in HVPG from baseline to end of treatment. A baseline total bilirubin of <1.5 mg/dL was associated with a ≥20 percent decrease in HVPG (p=0.03). This study is the first to demonstrate the effect of direct acting antivirals like Sovaldi on HVPG, and additional assessments will be undertaken in these patients one-year post treatment. </p> <p>The safety and efficacy of these investigational uses of Harvoni and Sovaldi have not been established. </p> <p><b>Important Safety Information About Harvoni</b></p> <p><b>Warnings and Precautions</b></p> <p><b>Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone:</b> Amiodarone is not recommended for use with Harvoni due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia. </p> <p><b>Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: </b>Rifampin and St. John’s wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations. </p> <p><b>Related Products Not Recommended:</b> Harvoni is not recommended for use with other products containing sofosbuvir (Sovaldi). </p> <p><b>Adverse Reactions</b></p> <p>Most common (≥10 percent, all grades) adverse reactions were fatigue and headache. </p> <p><b>Drug Interactions</b></p> <p>In addition to rifampin and St. John’s wort, coadministration of Harvoni is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of Harvoni. </p> <p>Coadministration of Harvoni is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively. </p> <p>Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments. </p> <p><b>Important Safety Information About Sovaldi</b></p> <p><b>Contraindications</b></p> <p>Sovaldi combination treatment with ribavirin or with peginterferon alfa plus ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risk for birth defects and fetal death associated with ribavirin. Contraindications to peginterferon alfa and ribavirin also apply to Sovaldi combination treatment. Refer to the prescribing information of peginterferon alfa and ribavirin for a list of their contraindications. </p> <p><b>Warnings and Precautions</b></p> <p><b>Serious Symptomatic Bradycardia When Coadministered with Amiodarone and Another HCV Direct Acting Antiviral (DAA):</b> Amiodarone is not recommended for use with Sovaldi in combination with another DAA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia. </p> <p><b>Pregnancy:</b> Use with ribavirin or peginterferon alfa/ribavirin: Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Female patients of childbearing potential and their male partners must use two forms of non-hormonal contraception during treatment and for at least 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. Refer to the prescribing information for ribavirin. </p> <p><b>Use with Potent P-gp Inducers: </b>Rifampin and St. John’s wort should not be used with Sovaldi as they may significantly decrease sofosbuvir plasma concentration, reducing its therapeutic effect. </p> <p>Adverse Reactions </p> <p>Most common (≥20 percent, all grades) adverse reactions for: </p> <p>Sovaldi + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia, and anemia </p> <p>Sovaldi + ribavirin combination therapy were fatigue, and headache </p> <p><b>Drug Interactions</b></p> <p>In addition to rifampin and St. John’s wort, coadministration of Sovaldi is not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of sofosbuvir, reducing its therapeutic effect. </p> <p><b>About Gilead</b></p> <p>Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California. </p> <p><b>Forward-Looking Statement</b></p> <p>This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including that Gilead may observe unfavorable results from additional clinical trials involving Sovaldi and Harvoni for various difficult-to-treat patient groups, including patients with decompensated cirrhosis, fibrosing cholestatic hepatitis C and portal hypertension. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements. </p> <p><i>U.S. full Prescribing Information for Sovaldi and Harvoni is available at </i><a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.gilead.com&esheet=51085677&newsitemid=20150422006666&lan=en-US&anchor=www.gilead.com&index=1&md5=e4518e055eb7353831c57b5168eec23c"><i></i></a><i><a href="http://www.gilead.com/">www.gilead.com</a></i>. </p> <p><i>Sovaldi and Harvoni are registered trademarks of Gilead Sciences, Inc., or its related companies.</i></p> <p><i>For more information on Gilead Sciences, please visit the company’s website at </i><a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.gilead.com%2F&esheet=51085677&newsitemid=20150422006666&lan=en-US&anchor=www.gilead.com&index=2&md5=0ee477968364a89a5539090216be061e"><i></i></a><i><a href="http://www.gilead.com/">www.gilead.com</a></i><i>, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.</i></p> <p>Source: Gilead Sciences, Inc.</p> <p>Gilead Sciences, Inc. <br />Sung Lee, +1 650-524-7792 (Investors) <br />Nathan Kaiser, +1 650-522-1853 (Media) <br />Michele Rest, +1 650-577-6935 (Media)</p> <p><a href="http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=2039077" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-15183770277937190242015-04-23T01:15:00.001-04:002015-04-23T01:15:04.359-04:00Gilead Announces Data for Investigational, All-Oral, Pan-Genotypic Three-Drug Regimen of Sofosbuvir, GS-5816 and GS-9857 for Chronic Hepatitis C<p><a href="http://lh3.googleusercontent.com/-VWAIp92EcJw/VTh_01JBfCI/AAAAAAAANJ4/3hYgckQleZo/s1600-h/Gilead%25255B3%25255D.gif"><img title="Gilead" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="Gilead" src="http://lh3.googleusercontent.com/-wLgkr_e5vSI/VTh_1sOi26I/AAAAAAAANKA/tbJqS8CIvAQ/Gilead_thumb%25255B1%25255D.gif?imgmax=800" width="205" height="71" /></a></p> <p><i><b>-- Data Support Ongoing Trials Evaluating Shortened Course of Therapy --</b></i></p> <p>VIENNA, Austria--(BUSINESS WIRE)--Apr. 23, 2015-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced pre-clinical data and results from Phase 1 and Phase 2 studies supporting the development of an investigational all-oral, pan-genotypic regimen of Sovaldi<sup>®</sup> (sofosbuvir 400 mg/SOF), the investigational NS5A inhibitor GS-5816 and GS-9857, an investigational NS3/4A protease inhibitor. These data will be presented at the 50th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress™ 2015) in Vienna, Austria. </p> <p>In pre-clinical studies, GS-9857 demonstrated similarly potent antiviral activity against HCV replicons of all tested genotypes (1-6), as well as an improved resistance profile compared to other HCV protease inhibitors (ePoster #P0899). In a healthy volunteer study, GS-9857 demonstrated a favorable pharmacokinetic profile (ePoster #P0861). Data from a three-day monotherapy study also demonstrated that GS-9857 was well-tolerated and achieved median HCV RNA reductions of more than 3 log10 IU/mL for HCV patients with genotypes 1, 2, 3 and 4 at the 100 mg dose (ePoster #P0901). </p> <p>Presented as a late-breaker ePoster (ePoster #LP03), a Phase 2 study of triple-combination therapy with a fixed-dose combination of SOF/GS-5816 plus GS-9857 among genotype 1 patients demonstrated sustained virologic response (SVR12) rates following six weeks of treatment of 93 percent (n=14/15) among treatment-naïve, non-cirrhotic patients, 87 percent (n=13/15) among treatment-naïve, cirrhotic patients, and 67 percent (n=20/30) among those who had failed therapy with two or more direct-acting antiviral agents (DAAs). The four-week regimen resulted in a sub-optimal SVR12 rate of 27 percent (n=4/15). </p> <p>“These data support the ongoing development of GS-9857 and the potential for an all-oral, triple combination therapy containing Sovaldi, GS-5816 and GS-9857 to attempt to further reduce treatment duration for hepatitis C patients,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. “We are encouraged by the six-week SVR12 rates and other data presented at EASL demonstrating this regimen’s pan-genotypic potential, and have recently initiated additional Phase 2 studies to further evaluate the appropriate treatment duration of this regimen for all patients, regardless of genotype, including those who have failed prior therapy with directly acting antivirals and those with cirrhosis.” </p> <p>SOF/GS-5816 plus GS-9857 was generally well tolerated. There were no Grade 3 or 4 adverse events nor serious adverse events. The most frequent adverse events were nausea (25 percent), headache (24 percent) and fatigue (16 percent). Transient, asymptomatic, elevated lipase (Grade 3 or 4) occurred in four patients (5 percent). </p> <p>GS-5816 and GS-9857 are investigational products and their safety and efficacy have not been established. Additional information about these studies can be found at <a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.clinicaltrials.gov&esheet=51085678&newsitemid=20150422006654&lan=en-US&anchor=www.clinicaltrials.gov&index=1&md5=7367c4e624045ad8f01442604be56831">www.clinicaltrials.gov</a>. </p> <p><b>About Gilead</b></p> <p>Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California. </p> <p><b>Forward-Looking Statement</b></p> <p>This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that Gilead may observe unfavorable results from additional clinical trials involving GS-9857, including in combination with Sovaldi and GS-5816. In addition, Gilead may make a strategic decision to discontinue development of GS-9857, including in combination with Sovaldi and GS-5816 if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. As a result, GS-9857 may never be successfully commercialized. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements. </p> <p><i>U.S. full Prescribing Information for Sovaldi is available at </i><a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.gilead.com&esheet=51085678&newsitemid=20150422006654&lan=en-US&anchor=www.gilead.com&index=2&md5=4d85ef45f2d8298936a4846b2b6192e7"><i></i></a><i><a href="http://www.gilead.com/">www.gilead.com</a></i>. </p> <p><i>Sovaldi is a registered trademark of Gilead Sciences, Inc., or its related companies.</i></p> <p><i>For more information on Gilead Sciences, please visit the company’s website at </i><a href="http://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.gilead.com%2F&esheet=51085678&newsitemid=20150422006654&lan=en-US&anchor=www.gilead.com&index=3&md5=1fade477284b59ea596db52442f9a73f"><i></i></a><i><a href="http://www.gilead.com/">www.gilead.com</a></i><i>, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.</i></p> <p>Source: Gilead Sciences, Inc.</p> <p>Gilead Sciences, Inc. <br />Sung Lee, +1 650-524-7792 (Investors) <br />Nathan Kaiser, +1 650-522-1853 (Media) <br />Michele Rest, +1 650-577-6935 (Media)</p> <p><a href="http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=2039076" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0tag:blogger.com,1999:blog-2424607637992982887.post-55506810683184812952015-04-22T19:19:00.001-04:002015-04-22T19:20:08.542-04:00The EASL Releases New Recommendations on the Treatment of Hepatitis C 2015<p>April 21, 2015</p> <p>The European Association for the Study of the Liver releases new recommendations for treating Hepatitis C.</p> <p>“These EASL Recommendations on Treatment of Hepatitis C are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with acute and chronic HCV infections.”</p> <p><font size="2">You can view the <strong>Summary</strong> ebook </font><a href="https://ilc-congress.eu/cpgs/summary/" target="_blank"><font size="2"><strong>here</strong></font></a><font size="2"> or download the PDF </font><a href="https://ilc-congress.eu/cpgs/summary/https://ilc-congress.eu/cpgs/EASL%20Recommendations%20on%20Treatment%20of%20Hepatitis%20C%202015%20-%20Summary.pdf" target="_blank"><font size="2"><strong>here</strong></font></a></p> <p><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgrEVfR_3Ug9PD4d78LJAMyduFH1_2zF_TQHRD1ySrakCQwjHwnfhDsczDu_NNoRElymDArlaMjUpT4GQrijlqgOHaWZg5SSUHQNHIPSDz1MhnAWxohQ0jzd6RkqKOpouaMyYWEs7AMIA/s1600-h/CPGs_summary%25255B3%25255D.jpg"><img title="CPGs_summary" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="CPGs_summary" src="http://lh3.googleusercontent.com/-coYw3_wioxY/VTgsfGaPvYI/AAAAAAAANJU/sZrVV-YEFoI/CPGs_summary_thumb%25255B1%25255D.jpg?imgmax=800" width="215" height="242" /></a></p> <p>or </p> <p>You can view the <strong>Full Version</strong> ebook <a href="https://ilc-congress.eu/cpgs_full/" target="_blank"><strong>here</strong></a> or download the PDF <a href="https://ilc-congress.eu/cpgs_full/EASL%20Recommendations%20on%20Treatment%20of%20Hepatitis%20C%202015.pdf" target="_blank"><strong>here</strong></a></p> <p><a href="http://lh3.googleusercontent.com/-Hxqnv-YgE2Q/VTgsfpw2iVI/AAAAAAAANJc/g9a9J5iMhMM/s1600-h/CPGs_full_version%25255B3%25255D.jpg"><img title="CPGs_full_version" style="border-top: 0px; border-right: 0px; background-image: none; border-bottom: 0px; padding-top: 0px; padding-left: 0px; border-left: 0px; display: inline; padding-right: 0px" border="0" alt="CPGs_full_version" src="http://lh3.googleusercontent.com/-VxLuxZQTkVY/VTgsgBV_znI/AAAAAAAANJg/YwckTb9y3RQ/CPGs_full_version_thumb%25255B1%25255D.jpg?imgmax=800" width="215" height="242" /></a></p> <p> </p> <p><a href="https://ilc-congress.eu/scientific-info/etools-ebooks-ilc2015/" target="_blank">Source</a></p> Hepatitis C Research and Newshttp://www.blogger.com/profile/17201491048437787105noreply@blogger.com0