HCV Research and News: April 2014

April 22, 2014

AbbVie Submits New Drug Application to U.S. FDA for its Investigational, All-Oral, Interferon-Free Therapy for the Treatment of Hepatitis C

-Submission based on the largest Phase III program in genotype 1 (GT1) hepatitis C patients conducted to date(1)

-AbbVie's investigational regimen was designated as a Breakthrough Therapy by the FDA

-AbbVie plans to submit applications for regulatory approval of its regimen in the European Union in early May

Apr 22, 2014

NORTH CHICAGO, Ill., April 22, 2014 /PRNewswire/ -- AbbVie (NYSE: ABBV) submitted its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval for the company's investigational, all-oral, interferon-free regimen for the treatment of adult patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection. The NDA is supported by data from the largest all-oral, interferon-free clinical program in GT1 patients conducted to date,¹ with six Phase III studies that included more than 2,300 patients in over 25 countries.

"This NDA submission is a significant advancement for AbbVie's HCV development program," said Scott Brun, M.D., vice president, Pharmaceutical Development, AbbVie. "Based on the robust data that have been generated in our international Phase III HCV program, we believe our all-oral, interferon-free regimen holds the potential to be a promising new therapy for patients living with this chronic infection."

In May of 2013, AbbVie's investigational direct-acting antiviral (DAA) regimen with and without ribavirin for HCV genotype 1 was designated as a Breakthrough Therapy by the U.S. FDA. This designation is intended to help expedite the development of drugs for serious or life-threatening conditions and is based in part on preliminary clinical evidence demonstrating a drug or regimen may have substantial improvement on at least one clinically significant endpoint compared to available therapy.

AbbVie plans to submit applications for regulatory approval of its regimen in the European Union in early May.

In the U.S., an estimated 3.2 million people are living with HCV and the infection is most prevalent among those born between 1945 and 1965.²

About AbbVie's Investigational HCV Regimen

The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ombitasvir (ABT-267) 25mg, dosed once daily, and dasabuvir (ABT-333) 250mg with or without RBV (weight-based), dosed twice daily. The combination of three different mechanisms of action interrupts the hepatitis C virus replication process with the goal of optimizing sustained virologic response rates across different patient populations.

Additional information about AbbVie's Phase III studies can be found on www.clinicaltrials.gov.

AbbVie's HCV Development Program

The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral regimen with and without ribavirin with the goal of producing high sustained virologic response rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis.

ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for hepatitis C virus protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of hepatitis C.

About AbbVie

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 approximately 25,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

Forward-Looking Statements

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 2013 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.

¹ Comparison based on review of data from www.clinicaltrials.gov for phase 3a programs of Gilead, BMS and BI as of November 15, 2013.

² Centers for Disease Control and Prevention. Hepatitis C FAQs for Health Professionals. 2013. http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm#section1. Accessed March 14, 2014.

SOURCE AbbVie

For further information: Media: Elizabeth Hoff, +1 (847) 935-4236, elizabeth.hoff@abbvie.com, Javier Boix, +1 (847) 937-6113, javier.boix@abbvie.com, or For Investor Relations: Liz Shea, +1 (847) 935-2211, liz.shea@abbvie.com

Source

April 12, 2014

Gut microbiota may play a role in the development of alcoholic liver disease

PUBLIC RELEASE DATE: 12-Apr-2014

Contact: Courtney Lock
courtney.lock@cohnwolfe.com
44-789-438-6422
European Association for the Study of the Liver

London, UK, Saturday 12 April 2014: Exciting new data presented today at the International Liver Congress™ 2014 shows that the gut microbiota has a potential role in the development of alcoholic liver disease (ALD).1 Though an early stage animal model, the French study highlights the possibility of preventing ALD with faecal microbiota transplantation – the engrafting of new microbiota, usually through administering human faecal material from a healthy donor into the colon of a recipient.2

In the study, two groups of germ-free mice received gut microbiota transplants from human representatives; one set from a patient with severe alcoholic hepatitis, the other from a patient with a history of alcohol abuse but without alcoholic hepatitis. The two sets of germ-free mice were then fed a liquid alcoholic diet.

The group that received microbiota from the patient with severe alcoholic hepatitis developed a more severe liver injury and a higher disruption of the intestinal mucosa in direct comparison to the group that received microbiota from the patient without severe alcoholic hepatitis. The study also identified two Clostridium bacteria that were able to produce ethanol in vitro and that were systematically associated with intestinal microbiota associated liver injury.

EASL Scientific Committee Member Prof. Frank Lammert commented: "Among heavy drinkers, the severity of alcoholic liver disease does not strictly correlate with the amount of alcohol intake, meaning that other factors must be influencing its development."

"These findings provide first evidence for a causal role of gut microbiota in alcohol-induced inflammation, and open up new avenues for the treatment of alcoholic liver disease with potentially better patient outcomes." At present, intestinal microbiota is considered to constitute a "microbial organ": one that has pivotal roles in the body's metabolism as well as immune function. Therefore transplantation aims to restore gut functionality and re-establish the homoestasis of intestinal flora.

The study was developed by an INRA-Micalis and INSERM/Paris-South University/Antoine-Béclère hospital collaboration.

###

Disclaimer: the data referenced in this release is based on the submitted abstract. More recent data may be presented at the International Liver Congress™ 2014.

Notes to Editors

About EASL

EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL 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.

EASL's main focus on education and research is delivered through numerous events and initiatives, including:

The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
Journal of Hepatology published monthly
Organisation of a Mentorship program and Masterclass to support young investigators starting out on their career path
Participation in a number of policy initiatives at European level

About The International Liver CongressTM 2014

The International Liver Congress™ 2014, the 49th annual meeting of the European Association for the study of the Liver, is being held at ExCel London from April 9 – 13, 2014. The congress annually attracts in excess of 9000 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on: Email: easlpressoffice@cohnwolfe.com

Helena Symeou +44 7976 562 430
Courtney Lock +44 7894 386 422

1. M. Llopis et al. INTESTINAL DYSBIOSIS EXPLAINS INTER-INDIVIDUAL DIFFERENCES IN SUSCEPTIBILITY TO ALCOHOLIC LIVER DISEASE. Abstract presented at the International Liver Congress™ 2014

2. Khoruts A and Sadowsky MJ, Therapeutic transplantation of the distal gut microbiota. Mucosal Immunology 2011; 4: 4-7

Source

Immunotherapy could help tackle tough liver cancer

PUBLIC RELEASE DATE: 11-Apr-2014 Contact: Courtney Lock
Courtney.Lock@cohnwolfe.com
44-789-438-6422
European Association for the Study of the Liver

London, England, Friday 11 April 2014 Significant new data presented today at the International Liver Congress™ 2014 indicate that liver cancer (Hepatocellular Carcinoma (HCC)) may be treated by adoptive T-cell therapy.

This new therapeutic approach in the treatment of HCC could be very important as without treatment the 5 year survival rate is just 5%. Globally, HCC accounts for 746,000 deaths, and in the UK alone is responsible for over 4,000 deaths per year.

Glypican-3 (GPC3) is a tumour associated antigen expressed in up to 70% of HCC but not in healthy human tissue. Isolating GPC3-specific T-cell receptors and expressing them on patient's T-cells can help treat HCC, as these T cells can recognise and eliminate GPC3-postive HCC.

The study detected and expanded MHC-multimer-positive CD8+ T-cells specific for targeted GPC3 epitopes and grew T-cell clones. From these clones, the most specific and active T-cell receptor was isolated. When this T-cell receptor was expressed on donor T cells it conferred specificity for GPC3, the HCC-associated antigen. Thus, it enables HLA-A2+ patient's T cells to specifically kill GPC3+ HCC.

Systemic treatments for advanced stage HCC are constantly evolving and current approaches include drug treatment with sorafenib - yet the current standard of care still does not offer a strong enough prognosis for patients. Liver transplant is an option for only 10 -15% of HCC carriers diagnosed at an early stage and therefore the importance of other treatment options for patients is critical. This is a treatment gap that adoptive T-cell therapy could potentially fill.

Disclaimer: the data referenced in this alert is based on the submitted abstract. More recent data may be presented at the International Liver Congress™ 2014.

###

Notes to Editors

About EASL

EASL's main focus on education and research is delivered through numerous events and initiatives, including:

The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of Hepatology
Journal of Hepatology published monthly
Organisation of a Mentorship program and Masterclass to support young investigators starting out on their career path
Participation in a number of policy initiatives at European level

About The International Liver CongressTM 2014

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:
Email: easlpressoffice@cohnwolfe.com

Helena Symeou +44 7976 562 430
Courtney Lock +44 7894 386 422

1. C.Dargel et al. T-CELL RE-DIRECTION AGAINST GLYPICAN-3 FOR IMMUNOTHERAPY OF HCC. Abstract presented at the International Liver CongressTM 2014

2. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F.GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet].Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr. Accessed 11.03.14

3. Liver Cancer Mortality Statistics http://www.cancerresearchuk.org/cancer-info/cancerstats/types/liver/mortality/uk-liver-cancer-mortality-statistics Accessed 11.03.14

4. Statistics and Outlook for Liver Cancer http://cancerhelp.cancerresearchuk.org/type/liver-cancer/treatment/statistics-and-outlook-for-liver-cancer. Accessed 11.03.14

Source

ProMetic's PBI-4050 Delivers New Positive Preclinical Results in Liver Fibrosis and Liver Cancer

LAVAL, QUEBEC, CANADA, - April 10, 2014 - ProMetic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF), ("ProMetic" or the "Corporation") presented new pre-clinical data at the 2014 annual meeting of the European Association for the Study of the Liver ("EASL") currently being held in London, UK. The new data supports the claim that PBI-4050's anti-fibrotic activity could also address various liver conditions such as non-alcoholic steatohepatitis ("NASH"), a condition affecting 2% to 5% of Americans, as well as liver cancer.

PBI-4050's favorable effect in reducing the progression of fibrosis in the liver was demonstrated in a gold standard animal model where liver fibrosis is induced by chronic administration of carbon tetrachloride ("CCL₄"), a chemical which at high chronic doses, causes irreversible damages to the liver and kidneys. Animals treated with PBI-4050 displayed a significant reduction of liver lesions as evidenced by histology and relevant biomarkers results. Following prolonged exposure to CCL₄, a significant number of the non-treated animals also developed hepatocellular carcinoma unlike those treated with PBI-4050.

"These results clearly indicate that PBI-4050's anti-fibrotic activity is at the core of the fibrosis regulation pathway in the liver", stated Dr. Lyne Gagnon, Head of Biology & Immunology at ProMetic.

Dr. John Moran, Chief Medical Officer at ProMetic stated "The progression from fibrosis to cirrhosis to hepatocellular carcinoma is well defined in humans. The positive effects observed with PBI-4050 in multiple challenging animal models bodes well for its potential use to treat various medical conditions involving and or leading to fibrosis."

The presentation at the EASL annual conference is available on the ProMetic website at: http://www.prometic.com/en/therapeutics/conferences.php

More on NASH:

Non-alcoholic steatohepatitis or NASH is a common, often "silent" liver disease. It resembles
alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and damage. Most people with NASH feel well and are not aware that they have a liver problem. Nevertheless, NASH can be severe and can lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer able to work properly. NASH affects 2 to 5 percent of Americans

More on Hepatocellular Carcinoma

Hepatic fibrosis is an outcome of many chronic liver diseases, including hepatitis B virus, hepatitis
C virus, alcoholic liver disease and non-alcoholic steatohepatitis. Liver fibrosis is characterized by the excess accumulation and alteration of extracellular matrix molecules, including collagen, in the tissue. Liver fibrosis can progress to liver cirrhosis, liver failure, portal hypertension and hepatocellular carcinoma. Liver transplantation is the only treatment available for patients with advanced stage of fibrosis.

About ProMetic Life Sciences Inc.

ProMetic Life Sciences Inc. (www.prometic.com) is a long established biopharmaceutical company with globally recognized expertise in bioseparations, plasma-derived therapeutics and small-molecule drug development. ProMetic offers its state of the art technologies for large-scale purification of biologics, drug development, proteomics and the elimination of pathogens to a growing base of industry leaders and uses its own affinity technology that provides for highly efficient extraction and purification of therapeutic proteins from human plasma in order to develop best-in-class therapeutics and orphan drugs. ProMetic is also active in developing its own novel small-molecule therapeutic products targeting unmet medical needs in the field of fibrosis, cancer and autoimmune diseases/inflammation. Headquartered in Laval (Canada), ProMetic has R&D facilities in the UK, the U.S. and Canada, manufacturing facilities in the UK and business development activities in the U.S., Europe and Asia.

Forward Looking Statements

This press release contains forward-looking statements about ProMetic's objectives, strategies and businesses that involve risks and uncertainties. These statements are "forward-looking" because they are based on our current expectations about the markets we operate in and on various estimates and assumptions. Actual events or results may differ materially from those anticipated in these forward-looking statements if known or unknown risks affect our business, or if our estimates or assumptions turn out to be inaccurate. Such risks and assumptions include, but are not limited to, ProMetic's ability to develop, manufacture, and successfully commercialize value-added pharmaceutical products, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of ProMetic to take advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. You will find a more detailed assessment of the risks that could cause actual events or results to materially differ from our current expectations in ProMetic's Annual Information Form for the year ended December 31, 2013, under the heading "Risk and Uncertainties related to ProMetic's business". As a result, we cannot guarantee that any forward-looking statement will materialize. We assume no obligation to update any forward-looking statement even if new information becomes available, as a result of future events or for any other reason, unless required by applicable securities laws and regulations. All amounts are in Canadian dollars unless indicated otherwise.

Source

Final Data from the Phase 2 COSMOS Study of Janssen’s Once-Daily Simeprevir in Combination with Sofosbuvir Presented at the International Liver Congress™

Additional Analyses Presented in European and Hepatitis C Genotype 4 Patient Subgroups Underscore Benefit of Simeprevir-based Treatment Regimens

April 12, 2014 11:24 AM Eastern Daylight Time

LONDON--(BUSINESS WIRE)--Janssen R&D Ireland (Janssen) today announced positive new data from the clinical development programme of simeprevir, including final data from cohort 2 of the Phase 2 COSMOS study of the protease inhibitor simeprevir administered once daily with Gilead Sciences Inc.’s nucleotide inhibitor sofosbuvir, with and without ribavirin (RBV), in adult patients chronically infected with genotype 1 hepatitis C virus (HCV). The final data, along with an additional analysis from COSMOS cohort 1 and new subgroup analyses of Phase 3 data in European and genotype 4 HCV patients, were presented at The International Liver Congress™ 2014 of the European Association for the Study of the Liver (EASL) in London.

“Following the recent positive opinion for simeprevir from the Committee for Medicinal Products for Human Use in the European Union, we look forward to bringing this regimen to patients in Europe in the near future.”

Final Phase 2 Data from the Interferon-free COSMOS Study
Cohort 2¹
Final results from cohort 2 of the Phase 2 COSMOS study* found that overall, 94 percent of genotype 1 treatment-naïve and prior null-responder HCV patients, with advanced liver fibrosis (METAVIR F3 or F4 scores) treated with simeprevir in combination with sofosbuvir, with or without RBV, for either 12 or 24 weeks achieved sustained virologic response 12 weeks after the end of treatment (SVR12). In patients treated with simeprevir and sofosbuvir alone, 93 percent and 100 percent of patients achieved SVR12 after 12 weeks and 24 weeks of treatment, respectively. The addition of RBV did not improve SVR rates; 93 percent of patients treated with the ribavirin-containing regimen achieved SVR12 after both 12 weeks and 24 weeks of treatment. Among HCV genotype 1a patients without Q80K, overall 97 percent of patients achieved SVR12 after 12 or 24 weeks of treatment regardless of treatment regimen, respectively. All patients with HCV genotype 1b achieved SVR12, regardless of treatment regimen or duration.

Among patients with baseline characteristics typically considered more difficult to treat, overall 98 percent of patients with the IL28B CT genotype, 95 percent of patients with the IL28B TT genotype, 95 percent of patients with METAVIR F4 scores, and 96 percent of genotype 1a patients with the Q80K polymorphism at baseline achieved SVR12. The most common adverse events reported during the study were fatigue, headache and nausea.

*Excluding non-virologic failures

Cohort 1²
An analysis of data from cohort 1 of the COSMOS study* demonstrated that overall 97 percent and 96 percent of genotype 1 HCV patients with METAVIR F0-F1 scores and F2 scores, respectively, treated with simeprevir and sofosbuvir alone achieved SVR12 after both 12 and 24 weeks of treatment. In patients treated with the ribavirin-containing regimen, 100 percent achieved SVR12 after 12 weeks and 24 weeks of treatment, respectively.

Among HCV genotype 1a patients with Q80K, 83 percent and 100 percent of patients treated with simeprevir and sofosbuvir alone achieved SVR12 after 12 or 24 weeks of treatment, respectively, compared to 89 percent of patients treated with simeprevir and sofosbuvir in combination with ribavirin. All patients with HCV genotype 1b achieved SVR12, regardless of treatment regimen or duration. Among patients with baseline characteristics typically considered more difficult to treat, overall 100 percent of patients with the IL28B CT genotype, 83 percent of patients with the IL28B TT genotype, and 100 percent of patients with IL28B CC genotype achieved SVR12. All patients without the Q80K polymorphism achieved SVR12, regardless of treatment regimen or duration. Adverse events (AEs) were mostly Grade 1/2 (77.5%); no serious AEs were reported, two patients discontinued treatment due to AEs.³

“The efficacy seen with the combination of simeprevir and sofosbuvir is very promising, especially considering the inclusion of patients with more advanced liver fibrosis in Cohort 2,” said Dr. Eric Lawitz, M.D., simeprevir clinical trial investigator, CEO at The Texas Liver Institute and Alamo Medical Research and Clinical Professor of Medicine at University of Texas Health Science Center. “I look forward to seeing the combination of simeprevir and sofosbuvir further evaluated in the recently initiated Phase 3 OPTIMIST trial.”

*Excluding non-virologic failures

Phase 3 Efficacy Data in European Patients with Genotype 4 Hepatitis C

Results from the Phase 3 RESTORE trial of simeprevir in combination with pegylated interferon and ribavirin in HCV genotype 4 treatment-naïve and treatment-experienced patients demonstrated that overall 65 percent of patients achieved SVR12, including 83 percent of treatment-naïve patients, 86 percent of prior relapsers, 60 percent of prior partial responders, and 40 percent of prior null responders. Among patients with genotype 4a and 4d HCV, 69 percent and 52 percent achieved SVR12, respectively.

In patients with the IL28B CT and TT genotypes, 66 percent and 60 percent achieved SVR12, respectively. Among patients with more severe liver fibrosis characterized by a METAVIR score of F3 or F4, 67 percent and 47 percent achieved SVR12, respectively. The most frequent adverse events included influenza-like illness, asthenia (weakness) and fatigue. Genotype 4 HCV is considered particularly difficult to treat and currently only limited treatment options are available.⁴

Subgroup Analyses of European Patients from Phase 3 Studies of Simeprevir

Analyses of pooled efficacy data from the QUEST-1 and QUEST-2 studies found 87 percent of European patients treated with simeprevir in combination with pegylated interferon (PegIFN) and RBV achieved SVR12, compared to 81 percent in the overall study population.⁵ In an analysis from the PROMISE study, 88 percent of European patients treated with simeprevir in combination with PegIFN and RBV achieved SVR12 compared to 79 percent in the overall study population.⁶

The efficacy of simeprevir in combination with pegylated interferon and ribavirin was also observed among European patients with baseline characteristics typically considered more difficult to treat. In QUEST-1 and QUEST-2, 71 percent of patients with METAVIR F4 scores, 86 percent of patients with the IL28B CT genotype, 69 percent of patients with the IL28B TT genotype and 64 percent of genotype 1a patients with the Q80K polymorphism at baseline achieved SVR12 in the simeprevir arm, compared to 25 percent, 44 percent, 31 percent and 50 percent of patients in the placebo arm, respectively. In PROMISE, 85 percent of patients with METAVIR F4 scores, 88 percent of patients with the IL28B CT genotype, 77 percent of patients with the IL28B TT genotype and 75 percent of genotype 1a patients with the Q80K polymorphism at baseline achieved SVR12 in the simeprevir arm, compared to 30 percent, 41 percent, 18 percent and 57 percent of patients treated in the placebo arm, respectively.^5,6

“The data presented at EASL further reinforce the benefit of simeprevir-based treatment across diverse patient populations, including European patients,” said Gaston Picchio, Hepatitis Disease Area Leader, Janssen Research & Development. “Following the recent positive opinion for simeprevir from the Committee for Medicinal Products for Human Use in the European Union, we look forward to bringing this regimen to patients in Europe in the near future.”

About Simeprevir

Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB and indicated for the treatment of chronic hepatitis C infection in combination with pegylated interferon and ribavirin in genotype 1 HCV infected patients with compensated liver disease, including cirrhosis.

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. Simeprevir was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan, in November 2013 in Canada and the U.S., and in March 2014 in Russia. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C and the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending Marketing Authorisation in the European Union for the use of simeprevir in combination with other medicinal products for the treatment of chronic HCV. This application is under review by the EMA.

About Hepatitis C

Hepatitis C (HCV) is a major global public health concern. It is a serious and complex blood-borne virus which manifests itself through complications of the liver. If left untreated, it can cause significant and potentially fatal damage to the liver including cirrhosis, leading to eventual transplantation. In Europe it is a leading cause of liver transplantation.⁷

The World Health Organisation (WHO) and the European Association for the Study of the Liver (EASL) estimate that 150 million people worldwide were chronically infected with HCV in 2011.⁸The virus is responsible for 350,000 deaths globally⁸ and 86,000 deaths in the European region each year.⁹ As the disease is often asymptomatic in its early stages it can be difficult to diagnose and treat. Up to 90 percent of those with HCV do not clear the virus without treatment and become chronically infected.¹⁰ The WHO estimates that 20 percent of people with HCV will develop cirrhosis and, of those, up to 20 percent may progress to liver cancer.¹¹Genotype 1 HCV is the most prevalent form of the virus worldwide¹² and one of the most challenging to treat successfully.

About Janssen Pharmaceutical Companies

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 http://www.janssenrnd.com for more information.

References
__________________________

¹ Lawitz M et al. The COSMOS cohort 2 study, abstract presented at the European Associate for the Study of the Liver (EASL) 2014.

² Sulkowski MS et al. The COSMOS study, oral presentation presented at the European Association for the Study of the Liver (EASL) 2014.

³ Sulkowski MS et al. The COSMOS study, abstract presented at the European Associate for the Study of the Liver (EASL)

⁴ Moreno C et al. The RESTORE study, abstract presented at the European Association for the Study of the Liver (EASL) 2014.

⁵ Foster GR et al. The QUEST 1 and 2, abstract presented at the European Association for the Study of the Liver (EASL) 2014.

⁶ Forns X et al. The PROMISE study, abstract presented at the European Association for the Study of the Liver (EASL) 2014.

⁷ European Association for the Study of the Liver. EASL The Burden of Liver Disease in Europe. Available from http://www.easl.eu/assets/application/files/54ae845caec619f_file.pdf. Accessed March 2014.

⁸ World Health Organisation. Hepatitis C. Fact sheet N. 164. Available at: http://www.who.int/mediacentre/factsheets/fs164/en/. Accessed March 2014.

⁹ Muhlberger M et al. HCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality. BMC Public Health 2009:9,34.

¹⁰ World Health Organisations (WHO). “Hepatitis C: About HCV Infection.” Available at: www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index3.html Accessed March 2014.

¹¹ World Health Organisation. Hepatitis C. Available at: http://www.who.int/csr/disease/hepatitis/Hepc.pdf. Accessed March 2014

¹² Zein NN. Clinical Significance of Hepatitis C Virus Genotypes. Clin. Microbiol. Rev. April 2000:13(2),223-235.

Contacts

Janssen EMEA
Media:
Hans Vanavermaete
Mobile: +32 (0) 478 447278
or
Rikki Jones
Mobile: +44 (0) 75 9591 9643
or
Investors:
Stan Panasewicz
Office: +1 (732) 524 2524
or
Louise Mehrotra
Office: +1 (732) 524 6491

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Also See: Final data from the phase II COSMOS study with Simeprevir in combination with Sofosbuvir presented at EASL (Medivirs’ Press Release)

Final data from the phase II COSMOS study with Simeprevir in combination with Sofosbuvir presented at EASL

Stockholm, Sweden — Medivir AB (OMX: MVIR) today announces that positive new simeprevir data were presented at The International Liver Congress™ 2014 of the European Association for the Study of the Liver (EASL) in London.
The data presented included;

Final phase II data from the interferon-free COSMOS study
Phase III efficacy data in patients with genotype 4 hepatitis C
Subgroup analyses of patients from phase III studies QUEST-1, QUEST-2 and PROMISE

Final phase II data from the interferon-free COSMOS study

Cohort 2
Final results from cohort 2 of the phase II COSMOS study demonstrated that 93 percent of prior null responder and treatment-naïve patients with genotype 1 HCV and advanced liver fibrosis (METAVIR scores F3 and F4) who were treated with simeprevir and sofosbuvir for 12 weeks achieved sustained virologic response 12 weeks after the end of treatment (SVR12). The addition of ribavirin did not improve SVR rates and consistent responses for both treatment arms were seen across HCV genotype subgroups after 12 weeks.

The most common adverse events reported during the study were fatigue, headache, nausea, anemia, pruritus, dizziness, rash and photosensitivity. One patient discontinued treatment due to adverse events.

Cohort 1
Previously presented data from cohort 1 at AASLD in November 2013, demonstrated that 96 percent and 93 percent of prior null responder patients with METAVIR F0-F2 scores treated with simeprevir and sofosbuvir without or with ribavirin, respectively, for 12 weeks achieved SVR12.

In genotype 1a patients with the Q80K polymorphism at baseline, 83 percent and 89 percent achieved SVR12 after 12 weeks of treatment without and with ribavirin, respectively. The most common adverse events reported during the study were fatigue, headache, nausea and insomnia. Two patients discontinued treatment due to adverse events.

Phase III efficacy data in patients with genotype 4 hepatitis C

Results from the Phase III RESTORE trial of simeprevir in combination with pegylated interferon and ribavirin in HCV genotype 4 treatment-naïve and treatment-experienced patients demonstrated that overall 65 percent of patients achieved SVR12, including 83 percent of treatment-naïve patients, 86 percent of prior relapsers, 60 percent of prior partial responders, and 40 percent of prior null responders. Among patients with more severe liver fibrosis characterized by a METAVIR score of F3 or F4, 67 percent and 47 percent achieved SVR12, respectively. Among patients with genotype 4a and 4d HCV, 69 percent and 52 percent achieved SVR12, respectively. The most frequent adverse events included influenza-like illness, asthenia (weakness) and fatigue.

Genotype 4 HCV is considered particularly difficult to cure and currently only limited treatment options are available.

Subgroup analyses of patients from phase III studies of Simeprevir

Analyses of pooled efficacy data from the QUEST-1 and QUEST-2 studies found 87 percent of European patients treated with simeprevir in combination with pegylated interferon and ribavirin achieved SVR12, compared to 80 in the overall study population. In an analysis from the PROMISE study, 88 percent of European patients treated with simeprevir in combination with pegylated interferon and ribavirin achieved SVR12 compared to 79 percent in the overall study population.

The efficacy of simeprevir in combination with pegylated interferon and ribavirin was also observed among European patients with baseline characteristics typically considered more difficult to cure. In QUEST-1 and QUEST-2, 71 percent of patients with METAVIR F4 scores, 86 percent of patients with the IL28B CT genotype, 69 percent of patients with the IL28B TT genotype and 64 percent of genotype 1a patients with the Q80K polymorphism at baseline achieved SVR12 in the simeprevir arm, compared to 25 percent, 44 percent, 31 percent and 50 percent of patients in the active placebo arm, respectively. In PROMISE, 85 percent of patients with METAVIR F4 scores, 88 percent of patients with the IL28B CT genotype, 77 percent of patients with the IL28B TT genotype and 75 percent of genotype 1a patients with the Q80K polymorphism at baseline achieved SVR12 in the simeprevir arm, compared to 30 percent, 41 percent, 18 percent and 57 percent of patients treated in the active placebo arm, respectively.

For more information please contact:

Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 17.15 CET on 12 April 2014.

About Simeprevir

Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB and indicated for the treatment chronic hepatitis C infection in combination with pegylated interferon and ribavirin in HCV genotype 1 and 4 infected patients with compensated liver disease, including cirrhosis.

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. Simeprevir was approved for the treatment of chronic hepatitis C infection as part of an antiviral treatment regimen in combination with pegylated interferon and ribavirin in genotype 1 infected adults with compensated liver disease, including cirrhosis in September 2013 in Japan, in November 2013 in Canada and the U.S. and in March 2014 in Russia. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C and the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending Marketing Authorisation in the European Union for the use of simeprevir in combination with other medicinal products for the treatment of chronic HCV. This application is under review by the EMA.

About Medivir

Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

Source

Hepatitis C treatment cures over 90 percent of patients with cirrhosis

PUBLIC RELEASE DATE: 12-Apr-2014

Contact: Will Sansom
sansom@uthscsa.edu
210-567-2579
University of Texas Health Science Center at San Antonio

Oral combination proves safe for patients who could not have interferon therapy

SAN ANTONIO, Texas (April 12, 2014) — Twelve weeks of an investigational oral therapy cured hepatitis C infection in more than 90 percent of patients with liver cirrhosis and was well tolerated by these patients, according to an international study that included researchers from UT Medicine San Antonio and the Texas Liver Institute. Historically, hepatitis C cure rates in patients with cirrhosis (liver scarring) have been lower than 50 percent and the treatment was not safe for many of these patients.

Hepatitis C virus is the No. 1 driver of cirrhosis, liver transplants and liver cancer in the United States, noted Fred Poordad, M.D., lead author on the study, which was released Saturday by The New England Journal of Medicine in conjunction with Dr. Poordad's presentation of the data at the International Liver Congress in London. UT Medicine is the clinical practice of the School of Medicine at The University of Texas Health Science Center at San Antonio, where Dr. Poordad is a professor of medicine. He is vice president of the Texas Liver Institute in San Antonio.

Interferon previously was the only agent to show effectiveness against hepatitis C, but patients often relapsed and the therapy caused multiple side effects. The new regimen is interferon-free and consists of several agents — ABT-450/ritonavir, ombitasvir, dasabuvir and ribavirin. Twelve weeks after the last dose, no hepatitis C virus was detected in the bloodstream of 91.8 percent of patients who took the pills for 12 weeks. Among patients treated for 24 weeks, 95.9 percent were virus-free 12 weeks after the end of therapy.

"These are out-of-the-ballpark response rates, not on the same planet as interferon," Dr. Poordad said. "The reason this study is so profound is because interferon is not tolerated nor is it safe in many people with cirrhosis. Many of the patients with cirrhosis in this study were not even eligible to be treated with interferon."

One of those patients was retired San Antonio anesthesiologist Sergio Buentello, M.D. Diagnosed with hepatitis C infection 11 years ago, Dr. Buentello had treatment with side effects and no cure eight years ago. "My viral count came down, but never to zero," he said.

When Eric Lawitz, M.D., of the Texas Liver Institute told him of the possibility of treatment with the new therapy, Dr. Buentello said he was skeptical. But as for so many others, the therapy worked.

"I feel very lucky to be living in this time, because I was almost resigned to the idea that I could never be cured," Dr. Buentello said.

The study examined outcomes in 380 patients at 78 sites, including hospitals and centers in Spain, Germany, England, Canada and the U.S. The biopharmaceutical company AbbVie provided support.

Investigators are cataloging patient blood samples for three years after therapy and so far have noticed no long-term, late relapses, Dr. Poordad said.

"Patients with advanced liver disease can now be cured of their hepatitis with a very well-tolerated and short regimen," he said.

The combination medication regimen is expected to be on the market as early as the end of 2014 or very early 2015.

###

For current news from the UT Health Science Center San Antonio, please visit our news release website, like us on Facebook or follow us on Twitter.

About UT Medicine San Antonio

UT Medicine San Antonio is the clinical practice of the School of Medicine at the UT Health Science Center San Antonio. With more than 700 doctors – all School of Medicine faculty – UT Medicine is the largest medical practice in Central and South Texas. Expertise is in more than 100 medical specialties and subspecialties. Primary care doctors and specialists see patients in private practice at UT Medicine's flagship clinical home, the Medical Arts & Research Center (MARC), located at 8300 Floyd Curl Drive, San Antonio 78229. Most major health plans are accepted, and UT Medicine physicians also practice at several local and regional hospitals. Call (210) 450-9000 to schedule an appointment, or visit http://www.UTMedicine.org for a list of clinics and phone numbers.

About the Texas Liver Institute

The Texas Liver Institute's mission is to set the standard of excellence in care and innovative research in the field of liver disease. The institute is affiliated with The University of Texas Health Science Center at San Antonio. The physicians are professors and teach at University Hospital of the University Health System and are involved with the liver transplantation program of the University Transplant Center, a partnership between the Health Science Center and the University Health System. For more information, visit http://www.txliver.com/.

Source

Also See: AbbVie to Present Late-Breaking Results from TURQUOISE-II Study in Chronic Hepatitis C Patients with Cirrhosis at the 2014 International Liver Congress™

Impressive SVR12 data for once-daily combination to treat HCV genotype 1 patients

PUBLIC RELEASE DATE: 12-Apr-2014 Contact: Courtney Lock
courtney.lock@cohnwolfe.com
44-789-438-6422
European Association for the Study of the Liver

High cure rates achieved with fixed-dose interferon-free and ribavirin-free regimen

London, UK, Saturday 12 April 2014: Results from three Phase III clinical trials (ION-1, ION-2 and ION-3) evaluating the investigational once-daily fixed-dose combination of the nucleotide analogue polymerase inhibitor sofosbuvir (SOF) 400mg and the NS5A inhibitor ledipasvir (LDV) 90mg, with and without ribavirin (RBV), for the treatment of genotype 1 chronic hepatitis C virus (HCV) infection have been presented at the International Liver CongressTM 2014.

"With cure rates well in excess of 90% with as little as eight weeks of treatment for some patients, these data represent a significant advance in the race to develop a new, all-oral treatment for Hepatitis C," said Professor Markus Peck-Radosavljevic, Secretary-General of the European Association for the Study of the Liver and Associate Professor of Medicine, University of Vienna, Austria.

"The results of the ION studies demonstrated highly satisfactory cure rates with a fixed dose combination of sofosbuvir/ledipasvir among patients with genotype 1 HCV infection without the use of either injectable interferon, which causes miserable flu-like symptoms, or ribavirin, an antiviral pill associated with a variety of troublesome side effects, including anaemia and rash," Professor Peck-Radosavljevic continued. "As a result of this marked improvement in tolerability, many more people are likely to seek treatment with this ribavirin-free regimen, which involves just one pill once a day."

Across the three ION studies, 1,952 patients with genotype 1 HCV infection were randomised to receive LDV/SOF with or without RBV for eight, 12 or 24 weeks of therapy. Of these, 1,512 patients were treatment-naïve, 440 were treatment experienced and 224 had compensated cirrhosis.

Of the 1,952 patients randomised in ION-1, ION-2 and ION-3, 1,886 patients (96.6%) achieved the primary efficacy endpoint of SVR12. Of the 66 patients (3.4%) who failed to achieve SVR12, 38 patients (1.9%) experienced virological failure: 36 due to relapse and two patients due to on-treatment breakthrough (with documented non-compliance). 28 patients (1.4%) were lost to follow-up.

Fewer adverse events were observed in the RBV-free, fixed-dose combination arms compared to the RBV-containing arms in all the ION studies. Adverse events observed in those taking LDV/SOF were generally mild and included fatigue and headache. In the RBV-containing arms of the ION studies, the most common adverse events were fatigue, headache, nausea and insomnia. Anaemia, which is a common side effect associated with RBV, was reported in 0.5% of patients in the LDV/SOF arms versus 9.2% of patients in the RBV-containing arms. Less than 1% of patients in the studies discontinued treatment due to treatment-emergent adverse events.

Genotype 1 is the most common, but hardest to treat, strain of the hepatitis C virus. Sofosbuvir belongs to a class of directly acting anti-viral (DAA) drugs known as nucleotide analogue polymerase inhibitors, which are designed to block an enzyme the hepatitis C virus needs to copy itself. Ledipasvir belongs to a promising new class of DAA drugs that work by blocking the NS5A protein, which the hepatitis C virus also needs to replicate.

ION STUDY SUMMARIES

ION-2 STUDY[i]

The ION-2 study evaluated 440 treatment-experienced genotype 1 HCV patients, including 88 with compensated cirrhosis, who had failed past therapy with regimens containing Peg-IFN (including Peg-IFN plus a protease inhibitor)
Patients received LDV/SOF with or without RBV for 12 or 24 weeks
After 12 weeks of therapy, SVR-12 was 96.4% and 93.6% for SOF+LDV+RBV and SOF+LDV
After 24 weeks of therapy, SVR-12 was 99.1% and 99.1% for SOF+LDV+RBV and SOF+LDV
One patient experienced on-treatment virological failure
No patients discontinued treatment due to an adverse event
Nine patients (2%) had treatment-emergent SAEs
Haemoglobin <10 g/dL occurred in 5% of patients taking LDV/SOF+RBV, and no patients taking LDV/SOF

ION-1 STUDY[ii]

The ION-1 study looked at 865 previously untreated patients, including 136 with cirrhosis
Patients received LDV/SOF with or without RBV for 12 or 24 weeks
After 12 weeks of therapy, SVR-12 was 97.2% and 98.6% for SOF+LDV+RBV and SOF+LDV
After 24 weeks of therapy, SVR-12 was 99.1% and 97.7% for SOF+LDV+RBV and SOF+LDV
The most frequent AEs reported for LDV/SOF were headache (25%), fatigue (23%), and nausea (12%)
33 patients (4%) had treatment-emergent SAEs
No patients receiving 12-Weeks of treatment and 10 patients receiving 24-Weeks of treatment discontinued therapy due to an AE
Haemoglobin <10 g/dL occurred in 8% of patients taking LDV/SOF+RBV and no patients taking LDV/SOF

ION-1 STUDY - Patient reported outcomes[iii]

Patient reported outcomes (PRO) were evaluated using: Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Work Productivity and Activity Index: Specific Health Problem (WPAI: SHP)
Throughout treatment, some of the PRO scores, especially those related to fatigue, activity and work productivity, were superior for RBV-free regimen (by up to 13.1%; p-values ≤0.5 to < 0.0001)
During treatment with the RBV-containing regimen, significant decrements in PROs were noted from baseline scores (up to -8.1%, p< 0.0001)
In contrast, most of PROs for the RBV-free regimens improved (up to +6.1%, p< 0.0001). This improvement was noted as early as treatment week 2, and maximised by end of treatment
Regardless of the regimen, patients who achieved SVR-12 showed significant improvement of PROs (+3.1% to +9.6%, p=0.045 to < 0.001)

ION-3 STUDY[iv]

In ION-3, 647 previously untreated patients without cirrhosis received LDV/SOF with or without RBV for 8 weeks or without RBV for 12 weeks
94% achieved SVR-12 after just eight weeks of treatment with LDV/SOF, rising to 95.4% with a 12-week regimen of LDV SOF.
There were no virological failures during treatment
Treatment was well tolerated: three patients discontinued due to adverse events
10 patients had SAEs: none were related to treatment
Haemoglobin <10 g/dL occurred in 5% of patients receiving LDV/SOF+RBV and in a single patient who received LDV/SOF

###

Disclaimer: the data referenced in this release is based on the submitted abstract. More recent data may be presented at the International Liver Congress™ 2014.

Notes to Editors

About EASL

EASL's main focus on education and research is delivered through numerous events and initiatives, including:

The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
Journal of Hepatology published monthly
Participation in a number of policy initiatives at European level

About The International Liver CongressTM 2014

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:
Email: easlpressoffice@cohnwolfe.com

Helena Symeou +44 7976 562 430
Courtney Lock +44 7894 386 422

[i] N.Afdhal et al. ALL ORAL FIXED-DOSE COMBINATION SOFOSBUVIR/LEDIPASVIR WITH OR WITHOUT RIBAVIRIN FOR 12 OR 24 WEEKS IN TREATMENT-EXPERIENCED GENOTYPE 1 HCV-INFECTED PATIENTS: THE PHASE 3 ION-2 STUDY. Abstract presented at the International Liver CongressTM 2014

[ii] A.Mangia et al. ALL ORAL FIXED-DOSE COMBINATION SOFOSBUVIR/LEDIPASVIR WITH OR WITHOUT RIBAVIRIN FOR 12 OR 24 WEEKS IN TREATMENT-NAIVE GENOTYPE 1 HCV-INFECTED PATIENTS: THE PHASE 3 ION-1 STUDY. Abstract presented at the International Liver CongressTM 2014

[iii] Z.Younossi et al. LEDIPASVIR (LDV) AND SOFOSBUVIR (SOF) COMBINATION IMPROVES PATIENT-REPORTED OUTCOMES (PRO) DURING TREATMENT OF CHRONIC HEPATITIS C (CH-C) PATIENTS: RESULTS FROM THE ION-1 CLINICAL TRIAL. Abstract presented at the International Liver CongressTM 2014

[iv] K.Kowdley et al. LEDIPASVIR (LDV) AND SOFOSBUVIR (SOF) COMBINATION IMPROVES PATIENT-REPORTED OUTCOMES (PRO) DURING TREATMENT OF CHRONIC HEPATITIS C (CH-C) PATIENTS: RESULTS FROM THE ION-3 CLINICAL TRIAL. Abstract presented at the International Liver CongressTM 2014

Source

New interferon-free, all-oral 3D regimen achieves high SVR in chronic HCV genotype 1 patients

PUBLIC RELEASE DATE: 12-Apr-2014 Contact: Courtney Lock
courtney.lock@cohnwolfe.com
44-789-438-6422
European Association for the Study of the Liver

London, UK, Saturday 12 April 2014: The new interferon-free, all-oral, three direct-acting-antiviral (3D) treatment regimen in development by AbbVie has achieved very high rates of virological response in patients chronically infected with hepatitis C virus (HCV) genotype 1 (GT1); according to the results of three studies presented today at the International Liver CongressTM 2014.

The 3D regimen consists of the HCV NS3/4A protease inhibitor ABT-450 dosed with ritonavir, the NS5A inhibitor ABT-267, and the NS5B RNA polymerase inhibitor ABT-333.

"Using this investigational 3D regimen, with or without ribavirin, these studies have demonstrated consistently high cure rates across a number of patient types, including the more difficult-to-treat subtype GT1a, and HCV patients with compensated cirrhosis," said EASL's Scientific Committee Member Dr. Alessio Aghemo, Gastroenterology and Hepatology Unit, Ospedale Maggiore Policlinico, University of Milan. "The impressive SVR12 results seen are consistent with the results from AbbVie's phase II studies," he added.

In the SAPPHIRE-I study, treatment naïve patients with chronic HCV GT1 infection and no evidence of liver cirrhosis, were given 12 weeks of treatment with the 3D regimen plus ribavirin (RBV). After 12 weeks, the overall intention-to-treat SVR12 rate was 96.2%. Even in the more difficult-to-treat subtype GT1a, which made up the majority of patients in this study, the SVR12 rate was 95.3% compared to 98% in GT1b patients.

Dr. Aghemo also presented the results from TURQUOISE-II, which demonstrated the efficacy of the 3D regimen even in HCV GT1a and GT1b patients with cirrhosis. Using an intention-to-treat analysis, in the 12 weeks treatment arm 91.8% of patients achieved SVR12; in the 24 weeks treatment arm, 95.9% of patients achieved SVR12.

Finally, a third study, PEARL-III, studying the efficacy and tolerability of AbbVie's investigational 3D regimen in treatment naïve adults with chronic genotype 1b (GT1b), and no evidence of liver cirrhosis, were randomised to receive the 3D regimen with or without (RBV). Following 12 weeks of treatment, 99.0% receiving the regimen without RBV and 99.5% receiving the regimen with RBV achieved SVR12.

"This collection of studies show encouraging data and further support our understanding of the efficacy and safety of this 3D regimen in a variety of patient types," summarised Dr Aghemo. "Such research continues to highlight the advances being made in treating complex diseases of this type."

Study 1: SAPPHIRE I: PHASE 3 PLACEBO-CONTROLLED STUDY OF INTERFERON-FREE, 12-WEEK REGIMEN OF ABT-450/R/ABT-267, ABT-333, AND RIBAVIRIN IN 631 TREATMENT-NAÏVE ADULTS WITH HEPATITIS C VIRUS GENOTYPE 1

Ninety-six percent SVR12 achieved in treatment naïve HCV Genotype 1 patients on investigational all-oral, interferon-free, 12-week regimen

In the 631-patient SAPPHIRE-I study, treatment-naïve patients chronically infected with HCV GT1, were treated with the 3D regimen plus ribavirin for 12 weeks. Patients were randomized to active treatment for 12 weeks or to start with a placebo for 12 weeks, followed by active treatment. The intention-to-treat SVR12 rate for the 3D regimen for those initially randomized to the active treatment arm was 96.2% (n=455/473). The final SVR12 results for those randomized to start with the placebo treatment are not yet available.

In the active treatment arm, patients with GT1b infection achieved 98 percent SVR12 (148/151), while patients with the more difficult-to-treat subtype GT1a achieved 95.3 percent SVR12 (307/322).

In this intent-to-treat analysis, patients with missing values for any reason were considered treatment failures. The rate of virological relapse or breakthrough was low, occurring in only 0.2% of patients during treatment with the 3D regimen and 1.5% of patients as a post-treatment relapse.

During the double-blind period, the most common treatment-emergent adverse events in the 3D and placebo arms were fatigue (34.7% and 28.5%, respectively) and headache (33.0% and 26.0%, respectively); the frequency of these events did not differ between treatment arms (P=NS). Discontinuation rates due to adverse events were low, and an equal percentage (0.6%) in both active and placebo groups.

"GT1 (with subtypes 1a and 1b) is the most prevalent HCV genotype worldwide," said Dr. Aghemo. "There is currently a large unmet need for a safe, efficacious and simple therapy in this patient population, and this SVR12 rate is superior to the historical SVR12 rate for telaprevir and peginterferon/ribavirin," he added.

The 3D regimen consisted of the NS5B RNA polymerase inhibitor ABT-333 (250mg), ribavirin (weight-based -- 1000mg or 1200mg daily), both dosed twice daily, and the fixed-dose combination of the HCV NS3/4A protease inhibitor ABT-450 (150mg) dosed with ritonavir (100mg) (ABT-450/r 150/100mg) co-formulated with the NS5A inhibitor ABT-267 (25mg).

Study 2: TURQUOISE-II: SVR12 RATES OF 92%-96% IN 380 HEPATITIS C VIRUS GENOTYPE 1-INFECTED ADULTS WITH COMPENSATED CIRRHOSIS TREATED WITH ABT-450/R/ABT-267 AND ABT-333 PLUS RIBAVIRIN (3D+RBV)

TURQUOISE-II demonstrates efficacy of 3D regimen even in HCV GT1 patients with cirrhosis

Finally, Dr. Aghemo presented the results from TURQUOISE-II the first completed phase III study investigating an all-oral, interferon-free regimen exclusively in GT1 cirrhotic patients.

From a global study population of 380 GT1a and GT1b, treatment-naive and treatment-experienced patients with compensated cirrhosis: 208 patients were randomised to the 3D regimen with ribavirin (RBV) for 12 weeks, and 172 patients randomised to the 3D regimen with RBV for 24 weeks.

Using an intention-to-treat analysis, in the 12 weeks treatment arm 91.8% of patients (n=191/208) achieved SVR12; in the 24 weeks treatment arm, 95.9% of patients (n=165/172) achieved SVR12. The difference between the two treatment arms was not statistically significant.

Virological relapse or breakthrough was noted in around 6% of patients in the 12-week arm and around 2 percent in the 24-week arm.

The three most common adverse events in the 12-week and 24-week treatment arms were respectively fatigue (32.7% and 46.5%), headache (27.9% and 30.8%) and nausea (17.8% and 20.3%). Discontinuations due to adverse events were noted in approximately 2% of subjects in both treatment arms. The safety profile was consistent with results in non-cirrhotic populations using the 3D with RBV regimen.

Study 3: PEARL-III: 12 WEEKS OF ABT-450/R/267 + ABT-333 ACHIEVED SVR IN >99% OF 419 TREATMENT-NAÏVE HCV GENOTYPE 1B-INFECTED ADULTS WITH OR WITHOUT RIBAVIRIN

PEARL-III demonstrates efficacy of 3D regimen with or without ribavirin for treatment of HCV GT1b-infected, non-cirrhotic, treatment-naive adults

This 419-patient studied 3D regimen with or without ribavirin (RBV), in adults with chronic genotype 1b (GT1b) who were new to treatment and had no evidence of liver cirrhosis. Following 12 weeks of treatment, 99.0 percent receiving the 3D regimen with placebo in place of RBV (n=207/209) and 99.5 percent receiving the regimen with RBV (n=209/210) achieved SVR12. High response rates were observed across all HCV GT1b patients in the study, including those patient populations with those characteristics (male gender, Black race and IL28B non-CC genotypes) historically associated with having a decreased response to treatment.

No on-treatment virological failures occurred in the treatment arm without RBV and one single virological failure occurred in the treatment arm with RBV. Across both treatment arms, there were no documented relapses within 12 weeks post-treatment.

###

Disclaimer: the data referenced in this release is based on the submitted abstracts. More recent data may be presented at the International Liver Congress™ 2014.

Notes to Editors

About EASL

EASL's main focus on education and research is delivered through numerous events and initiatives, including:

The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
Journal of Hepatology published monthly
Organisation of a Mentorship program and Masterclass to support young investigators starting out on their career path
Participation in a number of policy initiatives at European level

About The International Liver CongressTM 2014

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:
Email: easlpressoffice@cohnwolfe.com

Helena Symeou +44 7976 562 430
Courtney Lock +44 7894 386 422

1. JJ FELD, ET AL. SAPPHIRE I: PHASE 3 PLACEBO-CONTROLLED STUDY OF INTERFERON-FREE, 12-WEEK REGIMEN OF ABT-450/R/ABT-267, ABT-333, AND RIBAVIRIN IN 631 TREATMENT-NAÏVE ADULTS WITH HEPATITIS C VIRUS GENOTYPE 1. ABSTRACT PRESENTED AT THE INTERNATIONAL LIVER CONGRESS™ 2014

2. F POORDAD, ET AL. TURQUOISE-II: SVR12 RATES OF 92%-96% IN 380 HEPATITIS C VIRUS GENOTYPE 1-INFECTED ADULTS WITH COMPENSATED CIRRHOSIS TREATED WITH ABT-450/R/ABT-267AND ABT-333 PLUS RIBAVIRIN (3D+RBV). ABSTRACT PRESENTED AT THE INTERNATIONAL LIVER CONGRESS™ 2014

3. P FERENCI, ET AL. PEARL-III: 12 WEEKS OF ABT-450/R/267 + ABT-333 ACHIEVED SVR IN >99% OF 419 TREATMENT-NAÏVE HCV GENOTYPE 1B-INFECTED ADULTS WITH OR WITHOUT RIBAVIRIN. ABSTRACT PRESENTED AT THE INTERNATIONAL LIVER CONGRESS™ 2014

Source

Also See: AbbVie to Present Late-Breaking Results from TURQUOISE-II Study in Chronic Hepatitis C Patients with Cirrhosis at the 2014 International Liver Congress™

New Chinese herbal medicine has significant potential in treating hepatitis C

PUBLIC RELEASE DATE: 12-Apr-2014 Contact: Courtney Lock
courtney.lock@cohnwolfe.com
44-789-438-6422
European Association for the Study of the Liver

London, UK, Saturday 12 April 2014: Data from a late-breaking abstract presented at the International Liver CongressTM 2014 identifies a new compound, SBEL1, that has the ability to inhibit hepatitis C virus (HCV) activity in cells at several points in the virus' lifecycle.[i]

SBEL1 is a compound isolated from Chinese herbal medicines that was found to inhibit HCV activity by approximately 90%. SBEL1 is extracted from a herb found in certain regions of Taiwan and Southern China. In Chinese medicine, it is used to treat sore throats and inflammations. The function of SBEL1 within the plant is unknown and its role and origins are currently being investigated.

Scientists pre-treated human liver cells in vitro with SBEL1 prior to HCV infection and found that SBEL1 pre-treated cells contained 23 percent less HCV protein than the control, suggesting that SBEL1 blocks virus entry. The liver cells transfected with an HCV internal ribosome entry site (IRES)-driven luciferase reporter that were treated with SBEL1 reduced reporter activity by 50% compared to control. This suggests that that SBEL1 inhibits IRES-mediated translation, a critical process for viral protein production.

In addition, the HCV ribonucleic acid (RNA) levels were significantly reduced by 78 percent in HCV infected cells treated with SBEL1 compared to the control group. This demonstrates that SBEL1 may also affect the viral RNA replication process.

Prof. Markus Peck-Radosavljevic, Secretary-General of the European Association for the Study of the Liver and Associate Professor of Medicine, University of Vienna, Austria, commented: "People infected with hepatitis C are at risk of developing severe liver damage including liver cancer and cirrhosis. In the past, less than 20 percent of all HCV patients were treated because the available treatments were unsuitable due to poor efficacy and high toxicity. Recent advances means that we can now virtually cure HCV without unpleasant side effects. However, the different virus genotypes coupled with the complexity of the disease means there is still a major unmet need to improve options for all populations."

Professor Peck-Radosavljevic continued: "SBEL1 has demonstrated significant inhibition of HCV at multiple stages of the viral lifecycle, which is an exciting discovery because it allows us to gain a deeper understanding of the virus and its interactions with other compounds. Ultimately this adds to our library of knowledge that may bring us closer to improving future treatment outcomes."

HCV invades cells in the body by binding to specific receptors on the cell, enabling the virus to enter it.2 Once inside, HCV hijacks functions of the cell known as transcription, translation and replication, which enables HCV to make copies of its viral genome and proteins, allowing the virus to spread to other sites of the body.2 When HCV enters the host cell, it releases viral (+)RNA that is transcribed by viral RNA replicase into viral (-)RNA, which can be used as a template for viral genome replication to produce more (+) RNA or for viral protein synthesis. Once the viral RNA is transcribed, HCV initiates a process known as IRES-mediated translation, which allows the viral RNA to be translated into proteins by bypassing certain protein translation checkpoints that would normally be required by the host cell to start protein translation.[ii],[iii] Viral RNA is the genetic material that gives HCV its particular characteristics. This process enables the virus to take advantage of the host cell's protein translation machinery for its own purposes.

There are an estimated 150 million to 200 million people living with chronic HCV and more than 350,000 people die annually from HCV-related diseases.[iv] HCV is transmitted through blood contact between an infected individual and someone who is not infected. This can occur through needlestick injuries or sharing of equipment used to inject drugs.[v]

###

Disclaimer: the data referenced in this release is based on the submitted abstract. More recent data may be presented at the International Liver Congress™ 2014.

Notes to Editors

About EASL

EASL's main focus on education and research is delivered through numerous events and initiatives, including:

The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of Hepatology
Journal of Hepatology published monthly
Organisation of a Mentorship program and Masterclass to support young investigators starting out on their career path
Participation in a number of policy initiatives at European level

About The International Liver CongressTM 2014

For further information on the studies, or to request an interview, please do not hesitate to contact the EASL Press Office on:
Email: easlpressoffice@cohnwolfe.com

Helena Symeou +44 7976 562 430
Courtney Lock +44 7894 386 422

[i] C.W Lin et al. Multiple Effects Of Chinese Herbal Medicine SBEL1 On Hepatitis C Virus Life Cycle. Abstract presented at the International Liver Congress™ 2014

[ii] Scheel, T.K.H. and Charles M Rice, C.M. Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nature Medicine, 2013; 19: 837-849

[iii] Komar, A.A. and Hatzoglou. Cellular IRES-mediated translation. Cell cycle, 2011; 10 (2): 229-240

[iv] European Comission. Horizon 2020. Breaking the Hepatitis C lifecycle. February 2014. Available at http://ec.europa.eu/programmes/horizon2020/en/news/breaking-hepatitis-c-lifecycle Accessed 19.03.14.

[v] Centers for Disease Control and Prevention. Hepatitis C FAQs for the Public. 2014. Available at http://www.cdc.gov/hepatitis/c/cfaq.htm#cFAQ31 Accessed 19.03.14.

Source

AbbVie to Present Late-Breaking Results from TURQUOISE-II Study in Chronic Hepatitis C Patients with Cirrhosis at the 2014 International Liver Congress™

- In patients with compensated liver cirrhosis and genotype 1 (GT1) chronic hepatitis C virus (HCV) infection, a difficult-to-treat population, TURQUOISE-II demonstrated SVR(12) rates of 91.8 and 95.9 percent after 12 and 24 weeks of treatment, respectively

- TURQUOISE-II is the largest phase III study of an all-oral, interferon-free treatment regimen conducted to date exclusively in GT1 HCV patients with cirrhosis

- Results from TURQUOISE-II demonstrated high virologic response and similar tolerability profile as seen in GT1 patients in other AbbVie phase III studies

- Results from TURQUOISE-II were published online today in The New England Journal of Medicine

- AbbVie will also present detailed data from the phase II M12-999 study and phase III PEARL-III study

Apr 12, 2014

LONDON, April 12, 2014 /PRNewswire/ -- AbbVie (NYSE:ABBV) announced that new, detailed results from its hepatitis C development program will be presented today at the International Liver Congress^TM (ILC) 2014. Data from a pivotal phase III study, TURQUOISE-II, featured in the ILC press conference on Friday, will be presented as a late-breaker. Additionally, results from the study have been published online in The New England Journal of Medicine.

TURQUOISE-II is a global, multi-center, randomized, open-label study evaluating the efficacy and safety of 12 weeks or 24 weeks of treatment with AbbVie's regimen with ribavirin (RBV) in adult patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection with compensated liver cirrhosis. Patients achieved sustained virologic response rates 12 weeks post-treatment (SVR₁₂) of 91.8 percent and 95.9 percent in the 12-week and 24-week treatment arms, respectively. Patients in the study were either new to therapy or treatment-experienced (failed previous treatment with pegylated interferon and RBV).

"Results from the TURQUOISE-II study demonstrate that high SVR₁₂ rates can be achieved in GT1 patients with compensated liver cirrhosis in both 12-week and 24-week treatment durations," said Fred Poordad, M.D., lead clinical investigator for TURQUOISE-II and Clinical Professor of Medicine at the University of Texas Health Science Center at San Antonio. "These data are encouraging, as cirrhotic patients are often a difficult-to-treat population in the HCV community."

Discontinuation rates due to adverse events were 1.9 percent (four patients) and 2.3 percent (four patients) in the 12-week and 24-week arms, respectively. The most commonly reported adverse events (>10 percent in either arm) in TURQUOISE-II were fatigue, headache, nausea, pruritus, insomnia, diarrhea, asthenia, rash, cough, irritability, anemia and dyspnea.

On-treatment virologic failure occurred in one patient (0.5 percent) in the 12-week arm and three patients (1.7 percent) in the 24-week arm. In addition, 12 patients (5.9 percent) in the 12-week arm and one patient (0.6 percent) in the 24-week arm experienced relapse within 12 weeks post-treatment.

"We designed our comprehensive HCV clinical trial program to generate important information about treating a range of GT1 patients," said Scott Brun, M.D., Vice President, Pharmaceutical Development, AbbVie. "These data will help the medical community better understand the use of our regimen for specific patient types they encounter with GT1 infection in actual practice."

In addition, AbbVie will present the following at the ILC today:

PEARL-III late-breaker poster: A phase III study examining the AbbVie regimen for 12 weeks with or without RBV in non-cirrhotic GT1b HCV-infected adult patients who were new to therapy
M12-999 oral presentation: Interim results of a phase II study examining the AbbVie regimen with RBV for 24 weeks in non-cirrhotic adult liver transplant recipients with recurrent GT1 HCV infection

Additional information about AbbVie's studies can be found on www.clinicaltrials.gov.

About AbbVie's Investigational HCV Regimen
The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ombitasvir (ABT-267) 25mg, dosed once daily, and dasabuvir (ABT-333) 250mg with or without RBV (weight-based), dosed twice daily. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations.

AbbVie's HCV Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral regimen with and without RBV with the goal of producing high SVR rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis.

ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of HCV.

Safety Information for Ribavirin and Ritonavir
Ribavirin and ritonavir 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.

There are special safety considerations when prescribing these drugs in approved populations.

Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.

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.

See approved product labels for more information.

About AbbVie
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 approximately 25,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

Forward-Looking Statements
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.

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.

SOURCE AbbVie

For further information: Media: Elizabeth Hoff, +1 (847) 935-4236, elizabeth.hoff@abbvie.com, Javier Boix, +1 (847) 937-6113, javier.boix@abbvie.com, Investor Relations: Liz Shea, +1 (847) 935-2211, liz.shea@abbvie.com

Source

Therapy for Hepatitis C — The Costs of Success

The New England Journal of Medicine

Editorial

Jay H. Hoofnagle, M.D., and Averell H. Sherker, M.D.

April 12, 2014DOI: 10.1056/NEJMe1401508

Welcomed and exciting results from three large, controlled trials of different regimens of oral antiviral agents for chronic hepatitis C, genotype 1, have now been published in the Journal.1-3 The regimens all included the combination of ledipasvir and sofosbuvir, two new direct-acting antiviral agents with potent activity against hepatitis C virus (HCV). The two drugs were given as a single tablet once daily for 8, 12, or 24 weeks, with or without ribavirin. The results were consistent and striking: the various regimens yielded rates of sustained virologic response of 93% to 99%. The combination of ledipasvir and sofosbuvir alone (without ribavirin) for 12 weeks was associated with response rates of 94% in the ION-2 study and 99% in the ION-1 study.1,2 Extending therapy to 24 weeks increased the rate minimally (to 98% and 99%, respectively). In contrast, adding ribavirin provided no further benefit, regardless of duration. In previously untreated patients without cirrhosis, shortening the duration of therapy (without ribavirin) to 8 weeks did not lessen the rate of response (94%, vs. 95% with 12 weeks of therapy in the ION-1 study).3 Importantly, the single-tablet regimen was easy to administer and had few side effects; among the 539 patients who received ledipasvir and sofosbuvir alone for 12 weeks in these three trials, only 2 stopped therapy early because of adverse events.

The rates of response to ledipasvir and sofosbuvir were virtually the same in all subgroups of patients, regardless of patients' age, sex, race, liver-enzyme levels, HCV genotype (1a vs. 1b), preexisting antiviral resistance variants, or host genetic factors. Even in the difficult-to-treat patients who had not had a sustained response to a previous course of the most effective interferon-based therapies,4 the response rate at post-treatment week 12 was 94%. In this group of patients, the presence of cirrhosis was associated with a slightly lower response rate (88%, vs. 95% without cirrhosis), but with the longer course of treatment (24 weeks), these differences disappeared (100% in both groups).2 Preliminary studies with interferon-free drug combinations in patients with other HCV genotypes (2 or 3) suggest that high rates of response can be expected with those HCV strains as well.5

The combined results of the three trials include 1952 patients, of whom 97% had a sustained virologic response. Among the 3% who did not have a response, almost half were lost to follow-up or withdrew consent. Only 2 patients did not have an undetectable level of HCV RNA that was maintained during treatment (on-treatment virologic failure). Furthermore, the relapse rate after stopping therapy was only 2%. Relapses were more common with shorter courses of therapy: 5% of patients who received 8 weeks of treatment had a relapse, as did 2% of those who received 12 weeks and 0.2% of those who received 24 weeks of treatment. Trials focusing on retreatment of these rare patients with relapse are ongoing and will provide important guidance.

Ledipasvir and sofosbuvir are not the only promising antiviral agents for hepatitis C on the near horizon. Several other all-oral antiviral regimens have performed similarly in phase 2 studies, with sustained response rates in the range of 90% or higher.6,7 Thus, there are likely to be several options for oral therapy of hepatitis C within the next year.

The availability of effective, oral regimens of therapy for hepatitis C will lead to major changes in the management of this disease and probably affect both its morbidity and its mortality. Since the first use of antiviral therapy for chronic hepatitis C almost 30 years ago,8 treatment has been based on alpha interferon and was limited by the common and sometimes serious side effects of this cytokine, as well as the need for up to a year of therapy and the limited response rates of 50% or less, even among carefully selected patients. In patients with coexisting conditions such as human immunodeficiency virus (HIV) infection, an autoimmune disorder, solid-organ transplant, active substance abuse, or serious heart, renal, or psychiatric disease, interferon was usually contraindicated and, if given, had a high rate of adverse events and was often not effective. In real-life situations, fewer than half the HCV-infected persons qualify for interferon therapy, many patients decline treatment, and response rates can be far lower than 50%.9 Furthermore, the management of therapy requires physicians and health care staff with special expertise and experience. It is hardly surprising that, despite the availability of interferon-based therapy for more than 20 years, the mortality from hepatitis C in the United States has continued to increase and now exceeds that from HIV infection.10

The limitations and medical barriers to treatment, however, may now largely disappear. The ease of administration, short duration of treatment, and minimal side effects of all-oral regimens will probably mean that most persons will qualify for therapy. Collectively, these regimens promise to transform hepatitis C from a condition requiring complex, unsatisfactory therapies and specialist care to one that can be effectively treated and easily managed by a general physician with few contraindications and side effects.

Unfortunately, not all barriers to treatment will be lifted. The major limitation remaining will be economic. The current cost of a 12-week regimen of sofosbuvir alone is $84,000, or $1,000 per tablet.11 The addition of ledipasvir will add to the costs, and these estimates do not include expenses for diagnostic assays, monitoring, and physician visits.

The predicted costs of the new oral antiviral agents are as breathtaking as their effectiveness. Chronic hepatitis C is estimated to affect 3.2 million Americans, half of whom may not be aware that they are infected.12 Public health efforts are now under way to identify persons with HCV infection and to direct them to medical care.13 With the present estimates of costs, however, treating even half the HCV-infected persons in the United States would add billions of dollars to an already overburdened medical care system. Costs alone cast a pall over the stunning success in achieving the long-hoped-for goal of a safe and effective therapy for hepatitis C.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on April 12, 2014, at NEJM.org.

Source Information

From the Liver Diseases Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.

Source