Ledipasvir-sofosbuvir plus ribavirin for patients with genotype 1 HCV previously treated in clinical trials of sofosbuvir regimens

Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Viral Hepatitis

David Wyles^1,*, Paul Pockros², Giuseppe Morelli³, Ziad Younes⁴, Evguenia Svarovskaia⁵, Jenny C. Yang⁵, Phillip S. Pang⁵, Yanni Zhu⁵, John G. McHutchison⁵, Steven Flamm⁶ and Eric Lawitz⁷

DOI: 10.1002/hep.27814

© 2015 by the American Association for the Study of Liver Diseases

Publication History

Accepted manuscript online: 2 APR 2015 11:45AM EST
Manuscript Accepted: 26 MAR 2015
Manuscript Revised: 16 MAR 2015
Manuscript Received: 23 FEB 2015

Keywords: direct-acting antiviral agents; HCV NS5B polymerase inhibitor; retreatment

Abstract

Patients who fail to achieve sustained virologic response (SVR) after treatment with sofosbuvir plus ribavirin with or without peginterferon do not have established retreatment options. We conducted an open-label trial to assess the efficacy and safety of ledipasvir-sofosbuvir plus ribavirin in patients with genotype 1 HCV who did not achieve SVR after treatment in phase 2 and 3 trials of sofosbuvir regimens. We enrolled 51 patients at 24 sites in the United States. All patients received the fixed-dose combination tablet of ledipasvir-sofosbuvir once daily plus weight-based ribavirin (1000 or 1200 mg/day) for 12 weeks. The efficacy endpoint was the proportion of patients with SVR 12 weeks after discontinuation of therapy (SVR12). Of the 51 patients enrolled, 25 (49%) had previously received sofosbuvir plus peginterferon-ribavirin, 20 (39%) had received sofosbuvir-ribavirin, five (10%) had received sofosbuvir placebo plus peginterferon-ribavirin, and one (2%) received GS-0938 monotherapy. Fourteen (27%) had compensated cirrhosis at baseline, and 47 (92%) had non-CC IL28B genotypes. SVR12 was achieved by 50 of the 51 patients (98%) treated. Among the 45 patients who received sofosbuvir in prior treatment, 44 (98%) achieved SVR12. The only patient who did not achieve SVR12 was a patient with genotype 3a HCV who had been incorrectly genotyped as 1a in the previous study. Given the high rates of SVR12, no differences among patient subgroups were discernible. Of 51 patients, 41 (80%) experienced at least one adverse event, but most events were mild to moderate in severity. The most common adverse events were fatigue, headache, and diarrhea. One patient discontinued treatment due to an unrelated adverse event (bipolar disorder). Conclusion: Twelve weeks of ledipasvir-sofosbuvir plus ribavirin was an effective and safe treatment for patients who have not achieved SVR with prior regimens that included sofosbuvir. This article is protected by copyright. All rights reserved.

Source

Cost-Effectiveness and Budget Impact of Hepatitis C Virus Treatment With Sofosbuvir and Ledipasvir in the United StatesCost-Effectiveness of HCV Treatment With Sofosbuvir and Ledipasvir

Annals of Internal Medicine

17 March 2015, Vol 162, No. 6>

Original Research | 17 March 2015

Jagpreet Chhatwal, PhD; Fasiha Kanwal, MD, MSHS; Mark S. Roberts, MD, MPP; and Michael A. Dunn, MD

[+-] Article and Author Information

Ann Intern Med. 2015;162(6):397-406. doi:10.7326/M14-1336

Background: Sofosbuvir and ledipasvir, which have recently been approved for treatment of chronic hepatitis C virus (HCV) infection, are more efficacious and safer than the old standard of care (oSOC) but are substantially more expensive. Whether and in which patients their improved efficacy justifies their increased cost is unclear.

Objective: To evaluate the cost-effectiveness and budget impact of sofosbuvir and ledipasvir.

Design: Microsimulation model of the natural history of HCV infection.

Data Sources: Published literature.

Target Population: Treatment-naive and treatment-experienced HCV population defined on the basis of HCV genotype, age, and fibrosis distribution in the United States.

Time Horizon: Lifetime.

Perspective: Third-party payer.

Intervention: Simulation of sofosbuvir–ledipasvir compared with the oSOC (interferon-based therapies).

Outcome Measures: Quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and 5-year spending on antiviral drugs.

Results of Base-Case Analysis: Sofosbuvir-based therapies added 0.56 QALY relative to the oSOC at an ICER of $55 400 per additional QALY. The ICERs ranged from $9700 to $284 300 per QALY depending on the patient's status with respect to treatment history, HCV genotype, and presence of cirrhosis. At a willingness-to-pay threshold of $100 000 per QALY, sofosbuvir-based therapies were cost-effective in 83% of treatment-naive and 81% of treatment-experienced patients. Compared with the oSOC, treating eligible HCV-infected persons in the United States with the new drugs would cost an additional $65 billion in the next 5 years, whereas the resulting cost offsets would be $16 billion.

Results of Sensitivity Analysis: Results were sensitive to drug price, drug efficacy, and quality of life after successful treatment.

Limitation: Data on real-world effectiveness of new antivirals are lacking.

Conclusion: Treatment of HCV is cost-effective in most patients, but additional resources and value-based patient prioritization are needed to manage patients with HCV.

Primary Funding Source: National Institutes of Health.

Source

Gilead Announces Harvoni Study Results in Chronic Hepatitis C Patients with Advanced Liver Disease and Those Who Failed Prior Treatment

Published: Nov 11, 2014 8:02 a.m. ET

- High Cure Rates in Nearly 800 HCV Patients with Advanced Liver Disease -

BOSTON, Nov 11, 2014 (BUSINESS WIRE) -- Gilead Sciences, Inc. GILD, +0.55% today announced results from several Phase 2 and Phase 3 studies evaluating investigational uses of Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) for the treatment of chronic hepatitis C virus (HCV) infection in patients with limited or no treatment options, including patients with decompensated cirrhosis, patients with HCV recurrence following a liver transplant and patients who failed previous treatment with other direct acting antivirals. These data will be presented this week at the 65th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting2014) in Boston.

“Chronic hepatitis C patients with advanced liver disease are among the most difficult to cure and traditionally have had limited or no treatment options,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. “The data presented this week demonstrate that Harvoni provides high cure rates for patients with advanced liver disease, as well as for those who failed prior treatment with other antivirals, including sofosbuvir-based regimens.”

Harvoni was approved by the U.S. Food and Drug Administration and Health Canada in October 2014 and is the first once-daily single tablet regimen for the treatment of chronic HCV genotype 1 infection in adults. Applications are pending in the European Union, Japan and New Zealand.

Advanced Liver Disease

In a pooled analysis of Phase 2 and Phase 3 open-label studies (Oral #82) in more than 500 genotype 1 HCV infected patients with compensated cirrhosis who received Harvoni alone or with ribavirin (RBV) for 12 or 24 weeks, 96 percent of patients achieved sustained virologic response (SVR12). Patients who achieve SVR12 are considered cured of HCV infection.

Two prospective analyses from a Phase 2 open-label study (Study GS-US-337-0123) evaluating patients with decompensated cirrhosis and those with HCV recurrence following liver transplantation also are being presented. In the first subgroup (Oral #239), 108 genotype 1 and 4 infected patients with decompensated cirrhosis, including those with moderate hepatic impairment (Child-Pugh-Turcotte (CPT) Class B) and severe hepatic impairment (CPT Class C), received Harvoni plus RBV for 12 or 24 weeks. Overall, SVR12 rates were 87 percent (n=45/52) in the 12-week arm and 89 percent (n=42/47) in the 24-week arm.

The second subgroup (Oral #8) evaluated 12 or 24 weeks of Harvoni plus RBV among 223 genotype 1 and 4 patients who developed HCV recurrence following liver transplantation. Among non-cirrhotic patients, SVR12 rates were 96 percent (n=53/55) and 98 percent (n=55/56) following 12 and 24 weeks of treatment, respectively. For patients with compensated cirrhosis, SVR12 rates were 96 percent for both 12 weeks (n=25/26) and 24 weeks (n=24/25) of therapy. SVR12 rates among patients with decompensated cirrhosis were 81 percent for both 12 weeks (n=25/31) and 24 weeks (n=17/21) of therapy.

Retreatment of Patients Who Failed Prior Therapy

Study GS-US-337-0121 (Late Breaker Oral #LB-6) evaluated 155 genotype 1 patients with compensated cirrhosis who had failed prior treatment with pegylated interferon (PegIFN)/RBV and subsequently PegIFN/RBV plus a protease inhibitor. In this study, patients were randomized (1:1) to receive Harvoni plus RBV for 12 weeks or Harvoni alone for 24 weeks. Ninety-six percent (n=74/77) of those receiving Harvoni plus RBV for 12 weeks and 97 percent (n=75/77) of those receiving Harvoni for 24 weeks achieved SVR12.

In a second study (Oral #235), 51 genotype 1 patients who previously failed SOF/PegIFN/RBV, SOF/RBV or a SOF placebo/PegIFN/RBV treatment regimen received Harvoni plus RBV for 12 weeks. Twenty-nine percent of study patients (n=15/51) had cirrhosis. Ninety-eight percent (n=50/51) achieved SVR12 following 12 weeks of treatment with Harvoni plus RBV.

In all of these studies, Harvoni was well tolerated and its safety profile was generally consistent with that observed in clinical trials of Harvoni. Adverse events included fatigue, headache, nausea and anemia, which was more common among patients taking RBV. Grade 3/4 laboratory abnormalities were infrequent and included decreases in hemoglobin, which is consistent with RBV-associated anemia.

The safety and efficacy of Harvoni have not been established for the investigational uses described above.

Additional information about these studies can be found at www.clinicaltrials.gov.

Important Safety Information About Harvoni

Warnings and Precautions

Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Rifampin and St. John’s wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.

Related Products Not Recommended: Harvoni is not recommended for use with other products containing sofosbuvir (Sovaldi).

Adverse Reactions

Most common (greater-than or equal to 10 percent, all grades) adverse reactions were fatigue and headache.

Drug Interactions

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.

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.

Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments.

About Gilead Sciences

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 worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.

Forward-Looking Statement

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 possibility of unfavorable longer-term results from these studies and other ongoing and subsequent clinical trials involving Harvoni, alone or in combination with other products, for the treatment of HCV in other patient populations. As Harvoni is used over longer periods of time, Gilead may find new issues such as safety or drug resistance, which may require it to provide additional warnings or contraindications in the label, which could reduce the market acceptance of Harvoni. 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 Quarterly Report on Form 10-Q for the quarter ended September 30, 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.

U.S. Full Prescribing Information for Harvoni is available at www.gilead.com.

Harvoni is a registered trademark of Gilead Sciences, Inc.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

SOURCE: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936 (Investors)
Cara Miller, 650-522-1616 (Media)

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Janssen Highlights its Hepatitis C Clinical Development Program in Advance of 2014 AASLD

Janssen Highlights its Hepatitis C Clinical Development Program in Advance of 2014 American Association for the Study of Liver Diseases (AASLD) Annual Meeting

-- Studies focused on patients where there is a high unmet need today or anticipated in the near future --

BOSTON, Nov. 7, 2014 /PRNewswire/ -- Janssen R&D Ireland (Janssen) highlights its hepatitis C (HCV) clinical development program in advance of The Liver Meeting^®, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), being held November 7-11, 2014 in Boston, Massachusetts.

Given the size, complexity and diversity of the HCV patient population, physicians will continue to need multiple treatment options and combinations in order to offer patients an opportunity for cure into the next decade.

The Janssen HCV clinical development program includes studies that investigate the use of simeprevir in several interferon-free regimens using selected combinations of direct-acting antivirals with different mechanisms of action targeting diverse patient populations. These studies are focused on potentially offering alternative and more immediate treatment options for physicians and patients where there is a high unmet need today or anticipated in the near future. Ongoing clinical studies include:

• Phase 3 OPTIMIST studies examining the safety and efficacy of simeprevir and the nucleotide analog NS5B polymerase inhibitor sofosbuvir without interferon or ribavirin for the treatment of chronic HCV infection for treatment-naïve and treatment-experienced patients with and without cirrhosis.
• Phase 2 IMPACT study evaluating the efficacy, safety and pharmacokinetics of simeprevir administered once daily in combination with sofosbuvir and the NS5A replication complex inhibitor daclatasvir in treatment-naïve and treatment-experienced patients with HCV genotype 1 and 4 infection and decompensated liver disease.

With the closing of the acquisition of Alios Biopharma, Inc. earlier today, Janssen now holds a platform of nucleotide analog polymerase inhibitors, the early-clinical stage compounds AL-335 and AL-516. 

"Janssen is committed to combating hepatitis C by exploring the potential to bring forth, in a timely manner, an in-house interferon-free combination regimen to make a difference in patients' lives," said Gaston Picchio, Ph.D., Hepatitis disease area leader, Janssen.

About Hepatitis C
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.

About Janssen Pharmaceutical Companies of Johnson & Johnson
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.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about OLYSIO^®?

• If you are pregnant, or plan to become pregnant, talk with your healthcare provider before taking OLYSIO^®. It is not known if OLYSIO^® will harm your unborn baby. Also read the Medication Guides for peginterferon alfa (Peg-IFN-alfa) and ribavirin (RBV) if your healthcare provider prescribes these medications for you in combination with OLYSIO^®.
  • Females must use an effective form of birth control during treatment with OLYSIO^®. Talk with your healthcare provider about birth control methods that you may use during treatment with OLYSIO^®.
• OLYSIO^® combination treatment may cause rashes and skin reactions to sunlight. These rashes and skin reactions to sunlight can be severe and you may need to be treated in a hospital. Rashes and skin reactions to sunlight are most common during the first 4 weeks of treatment, but can happen at any time during combination treatment with OLYSIO^®.
  • Use sunscreen, and wear a hat, sunglasses, and protective clothing when you will be exposed to sunlight during treatment with OLYSIO^®.
  • Limit sunlight exposure during treatment with OLYSIO^®.
  • Avoid use of tanning beds, sunlamps, or other types of light therapy during treatment with OLYSIO^®.
  • Call your healthcare provider right away if you get any of the following symptoms:
    • burning, redness, swelling or blisters on your skin
    • mouth sores or ulcers
    • red or inflamed eyes, like "pink eye" (conjunctivitis)

• You should not take OLYSIO^® alone. OLYSIO^® should be used together with other medicines to treat chronic hepatitis C infection.

What should I tell my healthcare provider before taking OLYSIO^®?

Before taking OLYSIO^®, tell your healthcare provider if you:

• have liver problems other than hepatitis C virus infection
• have ever taken any medicine to treat hepatitis C virus infection
• had a liver transplant
• are receiving phototherapy
• have any other medical condition
• are of East Asian descent
• are breastfeeding. It is not known if OLYSIO^® passes into your breast milk. You and your healthcare provider should decide if you will take OLYSIO^® or breastfeed. You should not do both.

• Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

• OLYSIO^® and other medicines may affect each other. This can cause you to have too much or not enough OLYSIO^® or other medicines in your body, which may affect the way OLYSIO^® or your other medicines work, or may cause side effects. Do not start taking a new medicine without telling your healthcare provider or pharmacist.

• Especially tell your healthcare provider if you take any of the following medicines (when taken by mouth or given by injection, where applicable): amiodarone (Cordarone^®, Pacerone^®), amlodipine (Norvasc^®), atazanavir (Reyataz^®), atorvastatin (Lipitor^®, Caduet^®), carbamazepine (Carbatrol^®, Epitol^®, Equetro^®, Tegretol^®), cisapride (Propulsid^®, Propulsid Quicksolv^®), clarithromycin (Biaxin^®, Prevpac^®), cobicistat-containing medicine (Stribild^®), cyclosporine (Gengraf^®, Neoral^®, Sandimmune^®), darunavir (Prezista^®), delavirdine mesylate (Rescriptor^®), dexamethasone, digoxin (Lanoxin^®), diltiazem (Cardizem^®, Dilacor XR^®, Tiazac^®), disopyramide (Norpace^®), efavirenz (Sustiva^®, Atripla^®), erythromycin (E.E.S.^®, Eryc^®, Ery‑Tab^®, Erythrocin^®, Erythrocin Stearate^®), etravirine (Intelence^®), felodipine (Plendil^®), flecainide (Tambocor^®), fluconazole (Diflucan^®), fosamprenavir (Lexiva^®), indinavir (Crixivan^®), itraconazole (Sporanox^®, Onmel^®), ketoconazole (Nizoral^®), lopinavir (Kaletra^®), lovastatin (Advicor^®, Altoprev^®, Mevacor^®), mexiletine (Mexitil^®), midazolam, milk thistle (Silybum marianum) or products containing milk thistle, nelfinavir (Viracept^®), nevirapine (Viramune^®, Viramune XR^®), nicardipine (Cardene^®), nifedipine (Adalat CC^®, Afeditab CR^®, Procardia^®), nisoldipine (Sular^®), oxcarbazepine (Oxtellar XR^TM,Trileptal^®), phenobarbital (Luminal^®), phenytoin (Dilantin^®, Phenytek^®), pitavastatin (Livalo^®), posaconazole (Noxafil^®), pravastatin (Pravachol^®), propafenone (Rythmol SR^®), quinidine (Nuedexta^®, Duraquin^®, Quinaglute^®), rifabutin (Mycobutin^®), rifampin (Rifadin^®, Rifamate^®, Rifater^®, Rimactane^®), rifapentine (Priftin^®), ritonavir (Norvir^®), rosuvastatin (Crestor^®), saquinavir mesylate (Invirase^®), sildenafil (Revatio^®, Viagra^®), simvastatin (Zocor^®, Vytorin^®, Simcor^®), sirolimus (Rapamune^®), St. John's wort (Hypericum perforatum) or products containing St. John's wort, tadalafil (Adcirca^®, Cialis^®), telithromycin (Ketek^®), tipranavir (Aptivus^®), triazolam (Halcion^®), verapamil (Calan^®, Covera‑HS^®, Isoptin^®, Tarka^®), voriconazole (Vfend^®).
• This is not a complete list of medicines that could interact with OLYSIO^®. Ask your healthcare provider or pharmacist if you are not sure if your medicine is one that is listed above.
• Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

What are the possible side effects of OLYSIO^®?

• The most common side effects in combination with Peg-IFN-alfa and RBV are skin rash, itching and nausea.

• The most common side effects in combination with sofosbuvir are tiredness, headache and nausea.

• Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of OLYSIO^®. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088.

When taking OLYSIO^® in combination with Peg-IFN-alfa and RBV, you should also read those Medication Guides. When taking OLYSIO^® in combination with sofosbuvir, you should also read its Patient Information leaflet.

Please see full Prescribing Information and Patient Information for more details.  

MEDIA CONTACTS:

Daniel de Schryver
+49 173 76 89 149
ddschryv@its.jnj.com

Ronan Collins
+47 488 425 00
Rcollin5@its.jnj.com

INVESTOR RELATIONS:
Stan Panasewicz
+1 732 524 2524

Louise Mehrotra
+1 732 524 6491

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Gilead Announces Results from Study of Sovaldi® for Retreatment of Chronic Hepatitis C in Patients Not Cured with Prior Antiviral Therapy

-- Results Demonstrate Efficacy of Sovaldi-Based Regimen in GT1 Infected Patients Who Failed Prior Therapy with Other Direct Acting Antivirals--

-- Data Support Retreatment with Sovaldi-Based Regimen in GT2 or GT3 Infected Patients Who Failed Prior Treatment with Sovaldi --

LONDON--(BUSINESS WIRE)--Apr. 10, 2014-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from an open-label clinical trial (Study GS-US-334-0109) evaluating once-daily Sovaldi^® (sofosbuvir) 400 mg tablets for the retreatment of chronic hepatitis C virus (HCV) infection among patients who failed prior therapy. These data will be presented in two oral sessions at the 49th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress 2014) in London.

In Study GS-US-334-0109 (Oral #55), patients with genotype 1 HCV infection (n=80) received 12 weeks of treatment with once-daily Sovaldi plus weight-based ribavirin (RBV) twice-daily (1,000 or 1,200 mg/day) and pegylated interferon (peg-IFN; 180 μg/week). Patients in the study had failed prior regimens containing peg-IFN, RBV and an investigational NS3 protease inhibitor, with or without investigational direct-acting antivirals (DAAs) (NS5A and/or non-nucleoside NS5B inhibitors). Forty-five percent of patients (n=36) had received more than one course of prior therapy, and 90 percent (n=72) had at least one viral mutation associated with HCV NS3, NS5A or NS5B drug resistance.

Among the 50 patients for whom sustained virologic response data was available 12 weeks after the end of treatment (SVR12), 74 percent (n=37/50) achieved SVR12. Additionally, 80 percent (n=28/35) of patients with baseline resistance against two or more DAAs achieved SVR12.

“This study demonstrates that Sovaldi-based regimens can achieve high cure rates even among hepatitis C patients who previously failed therapy with baseline resistance to at least two DAAs,” said Stanislas Pol, MD, PhD, Professor of Hepatology and Gastroenterology, Paris Descartes University, Paris, France, and a principal investigator. “Importantly, Sovaldi has now demonstrated efficacy among genotype 1 HCV infected patients who failed prior treatment with three or four drug regimens and have developed viral resistance to some of the components of those regimens.”

In a separate presentation (Oral #8), retreatment with Sovaldi in genotype 2 (n=11) or genotype 3 (n=96) HCV infected patients who previously failed treatment with 12 or 16 weeks of Sovaldi plus RBV in the Phase 3 studies FISSION, FUSION and POSITRON was evaluated. Thirty-six percent of these patients (39/107) had cirrhosis. Patients were retreated either with a 12-week regimen of Sovaldi, RBV and peg-IFN, or a 24-week, interferon-free regimen of Sovaldi plus RBV. The choice of regimen was determined by study investigators.

Among patients with available SVR12 data, 63 percent (n=25/40) of those who received the 24-week all-oral regimen and 92 percent (n=24/26) of those who received the 12-week regimen of Sovaldi, RBV, and peg-IFN achieved SVR12.

“These data support initial findings from the Phase 3 trials, which demonstrate that Sovaldi is an effective treatment option and one that may also be particularly important for genotype 2 and 3 patients who failed a previous sofosbuvir-based regimen,” said Rafael Esteban, MD, Head of the Internal Medicine and Liver Unit, Hospital Universitari Vall d’Hebron and Professor of Medicine, Universitat Autónoma de Barcelona, Barcelona, Spain and a principal investigator for the study.

Sovaldi was well tolerated in Study GS-US-334-0109. The most common adverse events were consistent with the safety profiles of peg-IFN and/or RBV. Additional information about the study can be found at www.clinicaltrials.gov.

About Sovaldi

Sovaldi is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. Sovaldi is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication.

Sovaldi was approved in the United States on December 8, 2013 and in the European Union on January 17. In the United States, Sovaldi is approved for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen. Efficacy has been established in subjects with HCV genotype 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection. Treatment response varies based on baseline host and viral factors. Monotherapy is not recommended for treatment of chronic hepatitis C. Study GS-US-334-0109 evaluated investigational uses of Sovaldi, for which safety and efficacy have not yet been established.

IMPORTANT SAFETY INFORMATION

Contraindications

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.

Warnings and Precautions

• Pregnancy: 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.

• Use with Potent P-gp Inducers: Rifampin and St. John’s wort should not be used with Sovaldi as they may significantly decrease sofosbuvir plasma concentration, reducing its therapeutic effect.

Adverse Reactions

Most common (≥20 percent, all grades) adverse reactions for:

• Sovaldi + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia, and anemia
• Sovaldi + ribavirin combination therapy were fatigue, and headache

Drug Interactions

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.

About Gilead Sciences

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 worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.

Forward-Looking Statement

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 possibility of unfavorable longer-term results from clinical trials evaluating Sovaldi for the treatment or retreatment of HCV, and the risk that healthcare providers, payers or insurers may not recognize the benefits of Sovaldi. As Sovaldi is used over longer periods of time by treatment-experienced patients with underlying health problems taking numerous other medicines, Gilead may find new issues such as safety, resistance or drug interaction issues, which may require it to provide additional warnings or contraindications in the label, which could reduce the market acceptance of Sovaldi. 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, 2013, 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.

U.S. full prescribing information for Sovaldi is available at www.gilead.com.

Sovaldi is a registered trademark of Gilead Sciences, Inc.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Patrick O’Brien, +1 650-522-1936 (Investors)
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Abbvie Demonstrates 96 Percent SVR(12) in its Phase III Study of Treatment-experienced Patients with Genotype 1 Hepatitis C

-RESULTS FURTHER CONFIRM PHASE II STUDIES, WITH CONSISTENT VIROLOGIC RESPONSE AND TOLERABILITY PROFILE-

- SAPPHIRE-II IS THE SECOND OF SIX PHASE III TRIALS STUDYING THE INVESTIGATIONAL 3D REGIMEN-

- FUTURE DATA ANTICIPATED FROM ABBVIE'S CLINICAL TRIALS EXAMINES 3D REGIMEN WITH AND WITHOUT RIBAVIRIN, AS WELL AS TREATMENT OF HEPATITIS C IN PATIENTS WITH CIRRHOSIS-

Dec 10, 2013

NORTH CHICAGO, Ill., Dec. 10, 2013 /PRNewswire/ -- AbbVie (NYSE: ABBV) released phase III results for the investigational three direct-acting-antiviral (3D) regimen plus ribavirin in patients with chronic, genotype 1 (GT1) hepatitis C virus (HCV) infection. In the 394-patient SAPPHIRE-II study, 96 percent of patients who previously failed pegylated interferon and ribavirin treatment, including approximately 49 percent of who were prior null responders, achieved sustained virologic response at 12 weeks (SVR₁₂) with the regimen. The majority of patients were GT1a, considered a difficult-to-treat subtype, and the SVR₁₂ rates of GT1a and GT1b were 96 percent and 97 percent, respectively. Virologic relapse or breakthrough was noted in 2 percent of patients receiving the 3D regimen plus ribavirin. In addition, the discontinuation rate due to adverse events was 1 percent.

Globally, approximately 160 million people are chronically infected with hepatitis C[1]. AbbVie's multinational HCV program is the largest all-oral, interferon-free clinical program in GT1 patients being conducted to date[2]. GT1 (with subtypes 1a and 1b) is the most prevalent genotype worldwide, with a higher prevalence of 1a in the U.S. and 1b in Europe.

"SAPPHIRE-II demonstrates that treatment-experienced genotype 1 HCV patients achieved high rates of virologic response with AbbVie's interferon-free, all-oral 3D regimen plus ribavirin," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Completion of the two placebo-controlled SAPPHIRE studies is an important step in AbbVie's HCV clinical development program.  We look forward to the results of studies looking at AbbVie's 3D regimen with and without ribavirin in different patients, as well as data from our dedicated study in patients with cirrhosis."

About Study M13-098 (SAPPHIRE-II)

Following SAPPHIRE-I, SAPPHIRE-II is the second placebo-controlled trial and the second of six phase III trials supporting AbbVie's investigational 3D regimen for the treatment of GT1 hepatitis C patients. AbbVie will disclose detailed SAPPHIRE-II results at future scientific congresses and in publications.

SAPPHIRE-II is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with ABT-333 (250mg), ribavirin (weight-based), both dosed twice daily, and the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg) and dosed once daily in non-cirrhotic, GT1a and GT1b HCV-infected, treatment-experienced adult patients who previously failed treatment with pegylated interferon and ribavirin.

The study population consisted of 394 GT1 treatment-experienced patients with no evidence of liver cirrhosis with 297 patients randomized to the 3D regimen plus ribavirin for 12 weeks, and 97 patients randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the 3D regimen plus ribavirin for 12 weeks. In the study, 49 percent of patients were prior null responders to pegylated interferon and ribavirin, generally considered among the most difficult to treat successfully.

Following 12 weeks of treatment with AbbVie's 3D regimen plus ribavirin, 96 percent (n=286/297) of patients achieved SVR₁₂ based on intent-to-treat analysis where patients with missing values for any reason were considered treatment failures. The SVR₁₂ rates in GT1a and GT1b patients were 96 percent (166/173) and 97 percent (119/123), respectively. One subject had HCV genotype 1 and achieved SVR₁₂, but was unable to be subgenotyped.

The most commonly reported adverse events in both the 3D and placebo arms were headache, fatigue and nausea. Discontinuations due to adverse events were reported in three (1 percent) patients receiving the 3D regimen and no patients receiving placebo. Virologic relapse or breakthrough was noted in 2 percent of patients receiving the 3D regimen plus ribavirin.  

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

AbbVie's HCV Development Program

The clinical program supporting our 3D regimen includes more than 2,300 GT1 patients in more than 25 countries around the world. The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral 3D regimen with or without ribavirin 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. Results from the remaining four studies in AbbVie's phase III program will be available in the coming months, supporting regulatory submissions starting in the second quarter of 2014.

Overview of AbbVie's phase III clinical program is as follows:

Overview of AbbVie's phase III clinical program is as follows:

Study	Patients (N)	Treatment Regimen	Treatment Duration
SAPPHIRE-I	GT1, treatment-naive (631)	ABT-450/rb +ABT-267c ABT-333 Ribavirin	12 weeks
		Placebo	12 weeks, then active treatment for 12 weeks
SAPPHIRE-II	GT1, treatment-experienced (394)	ABT-450/r +ABT-267 ABT-333 Ribavirin	12 weeks
		Placebo	12 weeks, then active treatment for 12 weeks
PEARL-II	GT1b, treatment-experienced (210 a)	ABT-450/r +ABT-267 ABT-333 Ribavirin	12 weeks
		ABT-450/r +ABT-267 ABT-333	12 weeks
PEARL-III	GT1b, treatment-naive (400 a)	ABT-450/r +ABT-267 ABT-333 Ribavirin	12 weeks
		ABT-450/r +ABT-267 ABT-333 Placebo	12 weeks
PEARL-IV	GT1a, treatment-naive (300 a)	ABT-450/r +ABT-267 ABT-333 Ribavirin	12 weeks
		ABT-450/r +ABT-267 ABT-333 Placebo	12 weeks
TURQUOISE-II	GT1, treatment-naive and treatment-experienced (with compensated cirrhosis) (380 a)	ABT-450/r +ABT-267 ABT-333 Ribavirin	12 weeks
		ABT-450/r +ABT-267 ABT-333 Ribavirin	24 weeks

^a projected study population

^b ABT-450/ritonavir

^c ABT-267 is co-formulated with ABT-450/r, administered as two pills once daily

The 3D regimen consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations. In May of 2013, AbbVie's investigational 3D regimen with and without ribavirin for HCV GT1 was designated as a Breakthrough Therapy by the U.S. Food and Drug Administration (FDA).

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, automimmune 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. 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. In 2013, AbbVie employs approximately 21,000 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 2012 Annual Report on Form 10-K/A, 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] Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011; 17(2):107-15. 

[2] Comparison based on review of data from clinicaltrials.gov for phase 3a programs of Gilead, BMS and BI as ofNovember 15, 2013

SOURCE AbbVie Inc.

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

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Simeprevir Administered Once Daily Demonstrates Sustained Virologic Response in Treatment-Naïve and Treatment-Experienced Genotype 1 Chronic Hepatitis C Patients

Janssen Therapeutics EMEA
Posted on: 12 Nov 13

Beerse, Belgium (Nov. 11, 2013) Janssen R&D Ireland (Janssen) today announced the presentation of new data for the new generation protease inhibitor simeprevir (TMC435) in the treatment of genotype 1 chronic hepatitis C (HCV) in treatment-naïve and treatment-experienced adult patients with compensated liver disease. In analyses of the Phase 3 QUEST-1 and QUEST-2 studies in treatment-naïve patients and the Phase 3 PROMISE study in prior relapse patients, the efficacy of simeprevir was observed in HCV patients considered difficult to treat, including patients with the IL28B TT genotype and METAVIR scores of F4.

HCV is a major problem in the EMEA region, where an estimated 15 million people are living with the disease.1 Many patients living with chronic HCV are in need of treatment and the genotype of the virus often determines how efficacious treatment will be.2

"Patients with certain baseline characteristics can be more likely to fail or relapse after prior treatment," said Ira Jacobson, M.D., simeprevir clinical trial investigator, chief of the Division of Gastroenterology and Hepatology, Vincent Astor Distinguished Professor of Medicine, Weill Cornell Medical College, and attending physician, New York-Presbyterian Hospital/Weill Cornell Medical Center, United States. "The breadth of simeprevir data presented at The Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) reinforce the potential of simeprevir as an effective treatment option in multiple patient populations, including patients who are considered difficult to treat, and will offer important guidance to physicians once simeprevir is approved."

On October 24, the U.S. Antiviral Drugs Advisory Committee of the FDA voted unanimously (19-0) to recommend simeprevir 150mg capsules administered once daily with pegylated interferon and ribavirin for the treatment of genotype 1 chronic HCV in adult patients with compensated liver disease. A Marketing Authorisation Application was submitted to the European Medicines Agency seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic HCV in April 2013. Simeprevir was approved in September 2013 in Japan, for the treatment of genotype 1 HCV. Simeprevir is also being studied in several interferon-free regimens using selected combinations of direct-acting antiviral agents with different mechanisms of action. UK/HCV/1113/0021

Pooled Analysis from QUEST-1 and QUEST-2 Confirms Clinical Benefit of Simeprevir in Sub-Populations of Patients (Abstract 1122)

In the Phase 3 QUEST-1 and QUEST-2 studies, 80% of treatment-naïve patients treated with simeprevir in combination with pegylated interferon and ribavirin achieved the primary endpoint of sustained virologic response 12 weeks after the end of treatment (SVR12) compared to 50% of patients treated with placebo plus pegylated interferon and ribavirin. The analysis, which included patients considered difficult to treat, found that 61% of patients with the IL28B TT genotype, 60% of patients with a METAVIR score of F4 and 75% of patients with genotype 1a HCV treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 21%, 34% and 47% of patients taking placebo plus pegylated interferon and ribavirin, respectively. Among patients with the genotype 1a Q80K polymorphism at baseline, 58% of patients treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 52% of patients treated with placebo in combination with pegylated interferon and ribavirin, but the difference was not statistically significant. 3% of patients treated with simeprevir discontinued treatment early due to an adverse event, compared to 2% of patients treated with placebo.

Analysis from PROMISE Reinforces Efficacy of Simeprevir in Sub-Populations of Patients (Abstract 1092)

In the pivotal Phase 3 PROMISE study, 79% of treatment-experienced HCV patients treated with simeprevir in combination with pegylated interferon and ribavirin who previously experienced a relapse after prior treatment with pegylated interferon-based therapy achieved the primary endpoint of SVR12 compared to 37% of patients treated with placebo plus pegylated interferon and ribavirin. In this sub-analysis, among patients considered difficult to treat, 65% of patients with the IL28B TT genotype, 74% of patients with a METAVIR score of F4 and 70% of patients with genotype 1a HCV treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 19%, 26% and 28% of patients taking placebo plus pegylated interferon and ribavirin, respectively. Among patients with the genotype 1a Q80K polymorphism at baseline, 47% of patients treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 30% of patients treated with placebo in combination with pegylated interferon and ribavirin. The most common adverse events in patients treated with simeprevir combined with pegylated interferon and ribavirin in the first 12 weeks were fatigue, headache and influenza-like illness.

"The data presented at AASLD offers further evidence of simeprevir’s efficacy in difficult to treat patient types," said Dr Maria Beumont, medical lead for simeprevir, Janssen. "Following the recent positive vote from the FDA’s Antiviral Drugs Advisory Committee to recommend approval of simeprevir, we look forward to making simeprevir available to patients living with chronic HCV in need of treatment in the near future, while we continue to evaluate the role of simeprevir as part of different HCV treatment combinations."

About Simeprevir

Simeprevir (TMC435) is a new generation NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, currently in Phase III development. Simeprevir works by blocking the viral protease enzyme that enables HCV to replicate in host cells. To date, more than 3,700 patients have been treated with simeprevir in clinical trials. UK/HCV/1113/0021 Page 3

Janssen Therapeutics EMEA, a division of Janssen Pharmaceutica NV has the commercialisation rights of simeprevir in Europe, Middle East & Africa. Medivir AB will commercialise the product in the Nordic countries.

In October, Janssen Pharmaceuticals, Inc. acquired the investigational compound GSK2336805, an NS5a replication complex inhibitor in Phase 2 development for the treatment of chronic HCV, from an affiliate of GlaxoSmithKline plc. Since being acquired, the compound has been renamed JNJ-56914845. Janssen Pharmaceuticals plans to initiate Phase 2 studies to evaluate the use of JNJ-56914845 in interferon-free combinations with simeprevir and TMC647055, the company’s non-nucleoside polymerase inhibitor, for the treatment of chronic HCV in adult patients with compensated liver disease.

For additional information about simeprevir clinical studies, please visit: https://www.clinicaltrialsregister.eu  or www.clinicaltrials.gov.

About Hepatitis C

Hepatitis C is a blood-borne infectious disease of the liver that affects approximately 150 million people worldwide, and causes 350,000 deaths annually.2 In the European region alone the incidence rate is 8.7 per 100,000 and leads to 86,000 deaths annually.1

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. It is the leading cause of primary liver cancers in Europe.3

About Janssen R&D Ireland

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.

Janssen Therapeutics EMEA is fully dedicated to HCV and simeprevir. Janssen-Cilag International NV is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit www.janssen-emea.com  and www.janssentherapeutics-emea.com   for more information. UK/HCV/1113/0021 Page 4

References

1. World Health Organisation Regional Office for Europe. Hepatitis data and statistics. http://www.euro.who.int/en/health-topics/communicable-diseases/hepatitis/data-and-statistics . Last accessed October 2013.

2. World Health Organisation Media Centre: Hepatitis C Fact Sheet No. 164; July 2013.

http://www.who.int/mediacentre/factsheets/fs164/en/ . Last accessed October 2013.

3. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. Journal of Hepatology 2011;55:245–264.

Editor's Details
Cendrine Banerjee-Quetel
GCI Health
http://GCI Health
+44 (0) 20 7072 4210
cendrine.banerjee-quetel@gcihealth.com

Last updated on: 12/11/2013

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VIDEO: Triple therapy with sofosbuvir yields high SVR rates among cirrhotic patients with HCV

Provided by Healio

November 7, 2013

WASHINGTON — Eric J. Lawitz, MD, of the Texas Liver Institute at the University of Texas, San Antonio, discusses the results of the LONESTAR-2 trial, presented during the Late-Breaking Abstract session at the Liver Meeting 2013.

The study evaluated the efficacy of 400 mg daily sofosbuvir with pegylated interferon and ribavirin for 12 weeks in a cohort of patients with hepatitis C genotype 2 and 3 who had failed previous therapy with peginterferon and ribavirin, including patients with and without cirrhosis.

The cohort had a sustained virologic response rate of 89%, with high response rates observed among patients with and without cirrhosis. Two virologic failures occurred, both among patients with HCV genotype 3, including one cirrhotic patient and one without cirrhosis.

Nearly all patients experienced adverse events, but the incidence of events did not increase compared with therapy containing peginterferon and ribavirin alone.

Disclosure: Lawitz reports numerous financial disclosures.

For more information:

Lawitz EJ. LB-4. Late-Breaking Abstract Session. Presented at: The Liver Meeting 2013; Nov. 1-5, Washington.

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Simeprevir Increases Rate of Sustained Virologic Response Among Treatment-Experienced Patients with HCV Genotype-1 Infection: a Phase IIb Trial

Gastroenterology

Article in Press

Stefan Zeuzem,Thomas Berg,Edward Gane,Peter Ferenci,Graham R. Foster,Michael W. Fried,Christophe Hezode,Gideon M. Hirschfield, Ira Jacobson,Igor Nikitin,Paul J. Pockros,Fred Poordad,Jane Scott,Oliver Lenz,Monika Peeters,Vanitha Sekar,Goedele De Smedt, Rekha Sinha,Maria Beumont-Mauviel

Received 4 July 2013; received in revised form 24 October 2013; accepted 29 October 2013. published online 04 November 2013.
Accepted Manuscript

Abstract

Background & Aims

Simeprevir (TMC435) is an oral NS3/4 protease inhibitor in Phase III trials for chronic hepatitis C virus (HCV) infection. We performed a Phase IIb, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the combination of simeprevir, peginterferon-α2a (PegIFN), and ribavirin (RBV) in patients with HCV genotype-1 infection previously treated with PegIFN and RBV.

Methods

We analyzed data from patients who did not respond (null response), had a partial response, or relapsed following treatment with PegIFN and RBV, randomly assigned to receive simeprevir (100 or 150 mg, once daily) for 12, 24, or 48 weeks plus PegIFN and RBV for 48 weeks (n=396), or placebo plus PegIFN and RBV for 48 weeks (n=66). All patients were followed for 24 weeks after planned end of treatment; the primary endpoint was the proportion of patients with sustained virologic response (undetectable HCV RNA) at that timepoint (SVR24).

Results

Overall, SVR24 rates were significantly higher in the groups given simeprevir than those given placebo (61%–80% vs 23%;P<.001), regardless of prior response to PegIFN and RBV (simeprevir vs placebo: prior null response, 38%–59% vs 19%; prior partial response, 48%–86% vs 9%; prior relapse, 77%–89% vs 37%). All groups had comparable numbers of adverse events; these led to discontinuation of simeprevir or placebo and/or PegIFN and RBV in 8.8% of patients given simeprevir and 4.5% of those given placebo.

Conclusions

In treatment-experienced patients, 12, 24, or 48 weeks simeprevir (100 mg or 150 mg once daily) in combination with 48 weeks PegIFN and RBV significantly increased rates of SVR24 compared to patients given placebo, PegIFN, and RBV and was generally well tolerated.

ClinicalTrials.gov number: NCT00980330

Keywords: direct-acting antivirals, DAA, clinical trial, SVR24

Abbreviations: AE, adverse event, ASPIRE, Antiviral STAT-C Protease Inhibitor Regimen in Experienced patients, AUC, area under the curve, BMI, Body Mass Index, EOT, End of treatment, FSS, Fatigue Severity Scale, HCV, hepatitis C virus, HIV, human immunodeficiency virus, IC50, median inhibitory concentration, LLOQ, lower limit of quantification, PegIFN, Peginterferon-α2a, PegIFN-α, Peginterferon-α,PILLAR, Protease Inhibitor TMC435 study assessing optimaL dose and duration as once-daiLy Antiviral Regimen, QD, once daily, RBV,ribavirin, RVR, rapid virologic response, SMV, simeprevir, SVR, sustained virologic response, SVR24, sustained virologic response at 24 weeks after the planned end of treatment, ULN, upper limit of normal

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