Gilead’s Sovaldi® Demonstrates Efficacy and Safety Among Chronic Hepatitis C Patients with Advanced Liver Disease

- Benefit in Patients with Decompensated Cirrhosis and Recurrent HCV Infection Following Liver Transplantation --

LONDON--(BUSINESS WIRE)--Apr. 11, 2014-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced data from two Phase 2 studies and a compassionate access study in which a regimen containing once-daily Sovaldi^® (sofosbuvir) 400 mg was administered for the treatment of chronic hepatitis C virus (HCV) infection in patients with advanced liver disease. These data are being presented this week at the 49th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress 2014) in London.

The first study, Study GS-US-334-0125 (Oral #068), is an ongoing open-label Phase 2 clinical trial evaluating HCV patients with cirrhosis and portal hypertension, with or without decompensation, who were randomized 1:1 to an immediate treatment arm in which Sovaldi and ribavirin (RBV) was administered for 48 weeks (n=25) or to a deferred treatment arm in which this regimen was initiated after a 24-week observation period (n=25). Eighty percent of participants were treatment-experienced.

Of the 22 patients who completed 24 weeks of therapy, 95 percent (n=21/22) achieved virologic suppression on treatment. Additionally, patients taking Sovaldi-based therapy experienced trends in clinical and laboratory parameter improvements compared to patients in the observation arm. Sovaldi-based therapy was well tolerated in the study, and only one patient discontinued treatment due to an adverse event. The most common adverse events occurring in more than 25 percent of patients included nausea and pruritis. Patients in both arms of the study will be followed to determine their 12-week sustained virologic response rates (SVR12) after 48 weeks of Sovaldi-based therapy.

Study GS-US-334-0126 (Poster #1232), was a single-arm open-label Phase 2 trial in which patients with established recurrent HCV infection following liver transplantation received up to 24 weeks of therapy with Sovaldi plus RBV (escalating doses starting at 400 mg/day). The majority of patients had genotype 1-HCV infection (n=33/40) and 88 percent (n=35/40) were treatment-experienced.

Seventy percent (n=28/40) of patients in this study achieved SVR12. The most common adverse events occurring in more than 20 percent of patients were fatigue, headache, arthralgia (joint pain) and diarrhea. There were no deaths, graft losses or episodes of organ rejection among post-liver transplantation patients, and no drug-drug interactions were reported between Sovaldi and immunosuppressive agents.

A third, compassionate access study (Oral #62), evaluated Sovaldi therapy among 104 post-transplant patients with severe recurrent HCV, including fibrosing cholestatic hepatitis, who had exhausted all other treatment options and received pre-approval access to Sovaldi via Gilead’s compassionate use program. Patients received up to 48 weeks of Sovaldi plus RBV, with some patients also receiving pegylated interferon (peg-IFN) (180 μg/week) at their physician’s discretion. The majority of patients in the study experienced clinical improvements on treatment. Overall, 62 percent of patients achieved SVR12. Sovaldi-based therapy was well tolerated.

“The patients included in these analyses are historically among the most difficult to cure, and many have had no appropriate treatment options until now,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. “These data demonstrate that Sovaldi-based oral therapy can improve outcomes, has a favorable safety profile and is well tolerated among hepatitis C patients with severe liver disease.”

Additional information about Study GS-US-334-0125 and Study GS-US-334-0126 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. Studies GS-US-334-0125 and GS-US-334-0126 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 of HCV among patients with advanced liver disease, and the risk that healthcare providers, payers or insurers may not recognize the benefits of Sovaldi over other agents. 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)
Cara Miller, +1 650-522-1616 (Media (U.S.))
Arran Attridge, +44 208 587 2477 (Media (Europe))

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New Data Reveals Positive Outcomes for Hep C Transplant Patients

London, United Kingdom, Friday 11 April 2014: New research announced at the International Liver Congress^TM 2014 today provides new hope for the notoriously difficult-to-treat population of liver transplant patients with recurring hepatitis C (HCV).^[1]

As part of a compassionate use program, 104 post-liver transplant patients with recurring HCV who had exhausted all treatment options and had poor clinical prognoses, received sofosbuvir (SOF) and ribavirin (RBV) with pegylated interferon (PEG) included at the physicians’ discretion for up to 48 weeks. Among patients whose clinical outcomes have been reported, 62% achieved SVR12. Additionally, 62% of patients had improvements in clinical conditions associated with hepatic decompensation (e.g., ascites and encephalopathy) and/or improvement in liver function tests. SOF+RBV±PEG was well-tolerated and led to high rates of virologic suppression.

EASL’s European Policy Councillor Professor Patrizia Burra of the Multivisceral Transplant Unit, Padova University Hospital, Padua, Italy said: “There are currently no effective treatment options for this patient group. However, this new trial involving the nucleotide polymerase inhibitor sofosbuvir (SOF) has demonstrated promising results, providing further evidence of its clinical potential.”

“For patients with advanced hepatitis C liver disease, liver transplants offer a second chance,” continued Professor Burra, “and for those who continue to suffer post-surgery, it’s important for us to keep following up all avenues possible to improve their quality of life.”

Other research revealed at the International Liver Congress^TM 2014 showed that most patients with mild hepatitis C recurrence diagnosed one year after liver transplant have excellent long-term outcomes.^[2]

In the second study, 172 patients who were diagnosed with mild hepatitis C recurrence one year after undergoing liver transplant surgery between 1999 and 2012 were followed for six and a half years with all relevant transplant-related, donor and recipient variables recorded. The cumulative probability of HCV-related graft loss five and 10 years after liver transplant were 3% and 10%, respectively.

However one third of these patients are still at risk of going on to develop cirrhosis, further demonstrating the need for antiviral therapy pre or post-transplant.

Hepatitis C infection is a common cause of liver transplantation, with virus-related diseases comprising 40% of primary indications for liver transplantation in Europe among patients with cirrhosis.^[3]

More than 5,500 liver transplantations are currently performed in Europe per year.^[3]

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.

- Ends -

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 Congress^TM 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 Congress^TM 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. X.FORNS ET AL. SOFOSBUVIR COMPASSIONATE USE PROGRAM FOR PATIENTS WITH SEVERE RECURRENTHEPATITIS C INCLUDING FIBROSING CHOLESTATIC HEPATITIS FOLLOWING LIVER TRANSPLANTATION. ABSTRACTPRESENTED AT THE INTERNATIONAL LIVER CONGRESS™ 2014

2. M.GAMBATO ET AL. LONG TERM OUTCOME OF MILD HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANTATION: A LARGEPROSPECTIVE STUDY. ABSTRACT PRESENTED AT THE INTERNATIONAL LIVER CONGRESS™ 2014

3. EU BURDEN OF LIVER DISEASE: A REVIEW OF AVAILABLE EPIDEMIOLOGICAL DATA. EUROPEAN ASSOCIATION FOR THE STUDYOF THE LIVER. 2013. HTTP://WWW.EASL.EU/ASSETS/APPLICATION/FILES/54AE845CAEC619F_FILE.PDF ACCESSED 16.02.14.

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Cost analysis of sofosbuvir/ribavirin versus sofosbuvir/simeprevir for genotype 1 HCV in interferon ineligible/intolerant individuals

Hepatology

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

Viral Hepatitis

Liesl M. Hagan^1,*, Mark S. Sulkowski² and Raymond F. Schinazi¹

DOI: 10.1002/hep.27151

Copyright © 2014 American Association for the Study of Liver Diseases

Keywords: Olysio; Sovaldi; direct-acting antiviral agent; interferon-free

Abstract

Background: Treatment guidance for chronic hepatitis C (CHC) released by the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) offer two options for interferon-ineligible/intolerant individuals with genotype 1 infection: sofosbuvir/ribavirin (SOF/RBV) for 24 weeks, or sofosbuvir/simeprevir (SOF/SMV) for 12 weeks. A 24-week course of SOF/RBV costs approximately US$169,000, with sustained virologic response (SVR) rates ranging from 52-84%; 12 weeks of SOF/SMV costs approximately $150,000, with SVR between 89% and 100%. Because SOF/SMV is currently used off-label, debate exists among physicians and payers about whether it should be prescribed and covered. This paper presents a cost-effectiveness analysis of these two treatment regimens accounting for costs of drugs, treatment-related medical care, re-treatment for individuals who do not achieve SVR, and natural history of continued HCV infection after failed re-treatment. The model uses a lifetime horizon and a societal perspective. Results: In the base case scenario, SOF/SMV dominated SOF/RBV in a modeled 50-year-old cohort of treatment-naïve and treatment-experienced subjects, excluding those who failed prior therapy with telaprevir or boceprevir. SOF/SMV yielded lower costs and more quality-adjusted life years (QALYs) for the average subject compared to SOF/RBV ($165,336 and 14.69 QALYs vs. $243,586 and 14.45 QALYs, respectively). In base case cost-analysis, the SOF/SMV treatment strategy saved $91,590 per SVR compared to SOF/RBV. Under all one-way sensitivity scenarios, SOF/SMV remained dominant and resulted in cost savings. Conclusions: These results suggest that a 12-week course of SOF/SMV is a more cost-effective treatment for genotype 1 CHC than 24 weeks of SOF/RBV among interferon-ineligible/intolerant individuals, supporting the AASLD/IDSA guidance and offering implications for both clinical and regulatory decision-making as well as pharmaceutical pricing. (Hepatology 2014;)

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HIV No Bar to HCV Therapy With New Agents

Published: Mar 4, 2014

By Michael Smith, North American Correspondent, MedPage Today

BOSTON -- New drugs for hepatitis C mean HIV co-infection is no longer a barrier to successful HCV treatment, researchers said here.

Three studies using different medications in co-infected patients all found cure rates similar to the same drugs in people who had only HCV, according to Douglas Dieterich, MD, of Mount Sinai Hospital in New York City.

"All of these drugs work remarkably well in co-infection," Dieterich told reporters at the annual Conference on Retroviruses and Opportunistic Infections.

Dieterich presented some details of phase III studies of faldaprevir, an investigational HCV protease inhibitor used with pegylated interferon-alfa and ribavirin; simeprevir (Olysio), a protease inhibitor approved for use with interferon and ribavirin; and sofosbuvir, an HCV NS5B inhibitor used with ribavirin.

All three medications are "direct-acting agents" -- they target aspects of viral replication, in contrast to interferon, which boosts the patient's immune system, and ribavirin, which is a general antiviral drug.

In all three studies, Dieterich said, the rate of cure was "exactly the same in co-infected patients as they are in mono-infected patients." A cure in the context of HCV is a sustained virologic response (SVR) -- defined as undetectable viral RNA at some prespecified point after ending therapy, usually 12 or 24 weeks.

The results of the trials are "good news" but not entirely surprising, commented Jean-Michel Pawlotsky, MD, PhD, of Henri Mondor University Hospital in Créteil, France, who moderated a press conference at which some details were presented.

Investigators had been seeing similar results with the first approved direct-acting agents, the protease inhibitors telaprevir (Incivek) and boceprevir (Victrelis), Pawlotsky told MedPage Today.

But treatment just with peginterferon and ribavirin -- for years the only available HCV therapy -- was more difficult for people who also had HIV. "The main difference was due to interferon," Pawlotsky said. "These patients were not responding well to interferon."

One implication, he said, is that in the future, separate trials in co-infected patients might not be needed in order to get approval for new direct-acting agents.

"A trial in mono-infected patients might lead to approval for co-infected patients as well," he said.

Dieterich said the so-called STARTVerso4 was intended to test the efficacy and safety of two different doses of faldaprevir, in combination with peginterferon and ribavirin, in 308 patients with genotype 1 of HCV.

Almost all the patients -- 96% -- were also on highly active antiretroviral therapy for HIV.

The overall SVR rate 12 weeks after the end of treatment (SVR₁₂), he said, was 72% and did not differ significantly between the two doses; phase III results in mono-infected patients were about 80%.

The simeprevir trial (dubbed Study C212) was also investigating the safety and efficacy of the drug among 108 HIV patients with genotype 1 HCV. The drug is approved for mono-infected patients.

In the trials used to support approval, the SVR rates were about 80% in treatment-naive and previously treated but relapsed patients, although they were lower -- 53% to 65% -- among patients who responded either partly or not at all to therapy with peginterferon and ribavirin.

In the co-infected cohort, Dieterich said, the SVR₁₂ rate was 74%. Interestingly, a mutation that usually predicts poor response to interferon -- the Q80K polymorphism -- had no effect, he said, although its presence made a significant difference among mono-infected patients.

In both studies, the drugs were well-tolerated, he said, and the safety profile was similar to what has been seen in mono-infected patients, with most of the adverse events related to interferon.

The final study, dubbed PHOTON-1, looked at sofosbuvir and ribavirin in 223 co-infected patients with several HCV genotypes and differing treatment status.

But overall, he said, SVR12 rates ranged from 70% to 90%, depending on genotype, and in most cases were "exactly the same as in mono-infected patients." SVR₂₄ rates did not change, except for one patient with genotype 1 who appeared to be re-infected after achieving SVR₁₂.

The regimen, he noted, is the first interferon-free regimen to be tested in HIV/HCV co-infected patients.

The regimen was well-tolerated, he said, with only a handful of patients stopping treatment owing to adverse events.

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The Rise of Sofosbuvir

Infectious Disease Special Edition
ISSUE: FEBRUARY 2014 | VOLUME: 1

by Kate O'Rourke

Many clinicians are ecstatic about the recent approval of sofosbuvir (Sovaldi, Gilead Sciences) for patients with hepatitis C virus (HCV) infection. At The Liver Meeting 2013, several presentations provided new insight into just how sofosbuvir will perform in clinical practice.

“I think sofosbuvir is the cat’s meow,” said Sammy Saab, MD, MPH, professor of medicine and surgery and head of outcomes research in hepatology at the David Geffen School of Medicine, University of California, Los Angeles.

“It’s a drug that has no resistance or incremental adverse effects. It is very well tolerated, very safe, very efficacious and there are no significant drug interactions with it. I think it is going to revolutionize the way we treat hepatitis in this country and around the world.”

Traditional Risk Factors Fade Away

According to studies presented at The Liver Meeting, many factors traditionally thought to portend poor outcomes in HCV patients may not have an effect with sofosbuvir. One study was a retrospective analysis of 982 patients with HCV infection (genotypes 1-6) in four Phase III trials: FISSION, POSITRON, FUSION and NEUTRINO. Patients were treated with sofosbuvir plus ribavirin, with or without pegylated interferon (IFN). Sustained virologic response (SVR) rates were analyzed according to gender, age (<65 vs. ≥65 years), interleukin-28 B (IL28B) genotype, body mass index (<30 vs. ≥30 kg/m²), race (black vs. non-black), viral load (HCV RNA <10⁷ vs. ≥10⁷ copies/mL), opiate replacement status and cirrhosis. Of these factors, only male gender and the presence of cirrhosis were consistently predictive of worse outcomes; the difference between cirrhotics and noncirrhotics existed but was not large. In the NEUTRINO trial, for example, 80% of cirrhotics versus 92% of noncirrhotics achieved SVR at week 12. Also, IL28B genotype status was only predictive of SVR in the NEUTRINO trial.

HIV Coinfection

Sofosbuvir in combination with ribavirin also works well and causes less toxicity than IFN-based regimens in HCV patients who are coinfected with HIV. In the PHOTON-1 trial, 182 treatment-naive patients with HCV genotype 1, 2 or 3 and stable HIV disease, some of whom had cirrhosis, were evaluated. SVR rates at week 12 were 81% in HCV genotype 2 patients and 67% in HCV genotype 3 patients. Among the 19 patients not acheiving SVR at week 12, relapse was confirmed in 12 patients and data were missing for six patients. HCV genotype 1 patients received 24 weeks of treatment and had an SVR rate of 76%. Sofosbuvir was coadministered effectively with multiple HIV antiretroviral regimens, including inhibitors of HIV-1 protease, reverse transcriptase and integrase; it had no adverse effect on HIV status or antiretroviral therapy.

“The IFN-free regimen of sofosbuvir plus ribavirin resulted in high SVR 12 rates in HCV treatment-naive, HIV-infected patients with HCV genotype 1, 2 or 3 coinfection,” said Mark Sulkowski, MD, medical director of the Viral Hepatitis Center in the Divisions of Infectious Diseases and Gastroenterology & Hepatology, and professor of medicine at the Johns Hopkins School of Medicine, in Baltimore, who presented the study. “SVR 12 rates were similar to those observed in patients with HCV mono-infection.”

Null Responders

Data from the COSMOS trial suggested that HCV genotype 1 null responders may be a lot easier to treat with the combination of sofosbuvir plus simeprevir (Olysio, Janssen) than with first-generation direct-acting antiviral agents. In this Phase II trial, investigators evaluated 167 patients in two cohorts. In cohort 1, patients with METAVIR scores of F0 to F2 who were prior null responders to IFN with ribavirin received 12 or 24 weeks of treatment with sofosbuvir plus simeprevir, with or without ribavirin. In an intent-to-treat (ITT) analysis of the data, these patients achieved SVR rates at week 12 of 79% to 96%. Cohort 2 included treatment-naive patients and prior null responders with METAVIR scores of F3 to F4; they received 12 weeks of treatment with sofosbuvir plus simeprevir, with or without ribavirin. These patients achieved SVR rates at week 4 of 96% to 100%, based on an ITT analysis. The treatments were characterized as generally well tolerated.

“The findings in this interim analysis suggest that the addition of ribavirin to simeprevir plus sofosbuvir may not be needed to achieve high rates of SVR in this patient population,” said Ira Jacobson, MD, chief of the Division of Gastroenterology and Hepatology at Weill Cornell Medical College, New York City, who presented the data. “Anemia and bilirubin increases were predominantly limited to the ribavirin-containing treatment arms.”

Cirrhosis

Results from the LONESTAR-2 trial echoed results of other trials showing the high efficacy of sofosbuvir in prior null responders and patients with cirrhosis. This trial tested 12 weeks of treatment with sofosbuvir plus pegylated IFN and ribavirin in treatment-experienced patients with HCV genotype 2 or 3 infection. HIV and HBV coinfected patients were excluded from the trial, but 50% of the study population had compensated cirrhosis. In patients with HCV genotype 2 (n=23), 93% of cirrhotics and 100% of noncirrhotics achieved SVR at week 12. In HCV genotype 3 patients, the presence of cirrhosis did not affect outcomes, and 83% of patients achieved SVR at week 12.

“Sofosbuvir plus pegylated IFN/ribavirin for 12 weeks demonstrated high efficacy in treatment-experienced genotype 2/3 patients who have historically low response rates and limited treatment options,” said Eric Lawitz, MD, vice president of scientific and research development at The Texas Liver Institute and clinical professor of medicine at the San Antonio University of Texas Health Science Center, who presented the study. “SVR rates were similar in patients with and without cirrhosis.”

Different Treatment Duration for Patients With HCV Genotypes 2 and 3

Although many of the traditional factors that predict treatment response in HCV patients do not seem to apply to sofosbuvir, there does seem to be a difference in response among HCV genotypes. In general, clinicians are accustomed to treating patients with HCV genotype 2 or 3 similarly, but these two groups respond differently to sofosbuvir.

In Phase III trials, response rates have been higher in patients with HCV genotype 2 after 12 weeks of treatment with sofosbuvir plus ribavirin. The VALENCE trial originally set out to test 12 weeks of treatment with sofosbuvir plus ribavirin in patients with HCV genotype 2/3, but investigators amended the trial after recognizing that the two types of patients might respond to treatment differently; the 250 patients with HCV genotype 3 ultimately received 24 weeks of treatment. Among genotype 3 patients without cirrhosis, response rates were 94% in treatment-naive patients and 87% in treatment-experienced patients; genotype 3 patients with cirrhosis had response rates of 60%.

More evidence that longer therapy is better for HCV genotype 3 patients came from data presented at a meeting of the FDA Sofosbuvir Review team on Oct. 25.

“The FDA did an elegant analysis of the effect of treatment duration with sofosbuvir–ribavirin in genotype 3–infected patients,” Dr. Sulkowski said. “[They] presented very convincing data that a 24-week duration of sofosbuvir–ribavirin should be the standard for all genotype 3–infected patients.”

The FDA analysis combined data from the FISSION, POSITRON, FUSION and VALENCE trials. In both treatment-naive and treatment-experienced patients with HCV genotype 3, SVR rates dramatically rose and relapse rates fell when treatment was increased from 12 weeks to 24 weeks (Table).

As a result, when the FDA approved sofosbuvir in December, the agency approved a 12-week treatment regimen in patients with HCV genotype 2 and a 24-week regimen in patients with genotype 3, both in combination with ribavirin. The FDA also approved a 12-week regimen of sofosbuvir in combination with ribavirin and IFN for patients with HCV genotypes 1 and 4.

---

Dr. Saab has served as a consultant and on the speakers’ bureaus for Boehringer Ingelheim, Genentech, Gilead Sciences, Janssen, Merck, and Vertex Pharmaceuticals. Dr. Sulkowski has received consulting fees from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Merck and Vertex. Dr. Jacobson has received grants or research support and has served as a member of a speaker’s bureau or as a consultant/advisor for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Idenix Pharmaceuticals, Janssen, Merck, Novartis, Roche/Genentech and Vertex. Dr. Lawitz has served on advisory committees or review panels for AbbVie, Achillion, BioCryst Pharmaceuticals, Biotica, Enanta, Idenix, Janssen, Merck, Novartis, Santaris, Theravance and Vertex; he has received grant and research support form AbbVie, Achillion, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Idenix, Intercept, Janssen, Merck, Novartis, Presidio, Roche, Santaris Pharma and Vertex.

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