FDA Approves Harvoni for Hepatitis C Patients with Advanced Liver Disease

The U.S. Food and Drug Administration (FDA) has approved an expanded indication for Gilead Sciences sofosbuvir/ledipasvir coformulation (Harvoni) plus ribavirin for genotype 1 chronic hepatitis patients with decompenated liver cirrhosis and for genotype 1 or 4 liver transplant recipients without cirrhosis or with compensated cirrhosis, the company announced this week.

The sofosbuvir (HCV polymerase inhibitor) and ledipasvir (HCV NS5A inhibitor) combination was initially approved for HCV genotype 1 in October 2014, and the FDA last year expanded the indication to include people with genotypes 4-6 and those with HIV/HCV coinfection.

The latest indication was based in part on data from the SOLAR-1 and SOLAR-2 trials. SOLAR-1 showed that sofosbuvir/ledipasvir plus ribavirin for 12 or 24 week cured more than 85%-89% of hepatitis C patients with decompensated cirrhosis. SOLAR-2 showed that this regimen produced sustained virological response rates of 85%-88% for patients with decompensated cirrhosis and 95%-98% for liver transplant recipients

Below is an edited excerpt from a Gilead press release describing the expanded indication in more detail.

U.S. FDA Approves Two Supplemental Indications for Harvoni in Chronic Hepatitis C Patients with Advanced Liver Disease

-- Liver Transplant Patients and Those with Decompensated Cirrhosis Can Now be Treated With 12 Weeks of All-Oral Therapy

Foster City, Calif. -- February 16, 2016 --Gilead Sciences, Inc. (NASDAQ: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved additional indications for Harvoni (ledipasvir/sofosbuvir) for use in chronic hepatitis C patients with advanced liver disease. Harvoni in combination with ribavirin (RBV) for 12 weeks was approved for use in chronic hepatitis C virus (HCV) genotype 1- or 4-infected liver transplant recipients without cirrhosis or with compensated cirrhosis (Child-Pugh A), and for HCV genotype 1-infected patients with decompensated cirrhosis (Child-Pugh B or C), including those who have undergone liver transplantation. Harvoni is now approved for use in a broader range of patient populations, including HCV genotypes 1, 4, 5 and 6, HCV/HIV-1 coinfection, HCV genotype 1 and 4 liver transplant recipients, and genotype 1-infected patients with decompensated cirrhosis.

"Hepatitis C-infected patients who have decompensated cirrhosis and those who have previously received a liver transplant have an urgent need for treatment, but historically their options have been limited," said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. "We are pleased that health care providers now have the information needed to offer these patients an all-oral, 12-week duration therapy with high cure rates and a tolerable side effect profile."

Decompensated Cirrhosis and Post-Liver Transplantation

The supplemental new drug application (sNDA) approval for genotype 1 or 4 HCV liver transplant recipients without cirrhosis or with compensated cirrhosis, and for genotype 1 HCV patients with decompensated cirrhosis, was supported by data from the Phase 2 SOLAR-1 and SOLAR-2 trials. These open-label studies evaluated 12 and 24 weeks of treatment with Harvoni in combination with RBV in HCV treatment-naive and treatment-experienced patients with genotype 1 and 4 infection who had undergone liver transplantation and/or who had decompensated liver disease.

Pooled data from SOLAR-1 and SOLAR-2 among genotype 1 HCV patients are summarized in the table below:

a. Five subjects transplanted prior to post-treatment Week 12 with HCV RNA<LLOQ at last measurement prior to transplant were excluded.

b. Two subjects were excluded due to failure to meet the inclusion criteria for any of the treatment groups (i.e., did not have decompensated cirrhosis and had also not received a liver transplant).

c. Twelve subjects were excluded from relapse analysis because they died (N=11) or withdrew consent (N=1) prior to reaching the 12 week post-treatment follow-up visit.

SVR12 rates among genotype 4 HCV post-transplant patients without cirrhosis or with compensated cirrhosis (n=12) were similar to the reported genotype 1 SVR12 rates; no subjects relapsed. Available data in subjects with genotype 4 HCV who had decompensated cirrhosis (pre- and post-liver transplantation) were insufficient for dosing recommendations.

A total of seven patients in the 12-week treatment arms of SOLAR-1 and SOLAR-2 had fibrosing cholestatic hepatitis (FCH), and all achieved SVR12. FCH is a rare and severe form of recurrent hepatitis that occurs following liver transplantation and is associated with high morbidity and mortality. Previously, there were no approved treatment options for FCH.

Adverse events observed in the two SOLAR studies were consistent with the expected clinical sequelae of liver transplantation and/or decompensated liver disease, or the known safety profile of Harvoni and/or RBV. Among liver transplant and decompensated liver disease patients, 1 percent and 2 percent of patients discontinued Harvoni with RBV due to an adverse event, respectively. The most common adverse reactions (>10 percent, all grades) observed with treatment with Harvoni in combination with RBV for 12 weeks were asthenia, headache and cough.

Important Safety Information for Harvoni

[See full press release]

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. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

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

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.

2/17/16

Sources

Gilead Sciences. U.S. FDA Approves Two Supplemental Indications for Harvoni in Chronic Hepatitis C Patients with Advanced Liver Disease. Press release. February 16, 2016.

R Klein, K Struble, and R Morin, U.S. Food and Drug Administration. Important changes to Harvoni affecting several categories of patients. FDA Hepatitis Update. February 12, 2016.