FDA Expands Harvoni Indication to Include Hepatitis C Genotypes 4-6 and HIV/HCV Coinfection

The U.S. Food and Drug Administration last week granted supplemental approval of Gilead Sciences' sofosbuvir/ledipasvir (Harvoni) single-tablet regimen for the treatment of hepatitis C virus genotypes 4, 5, and 6 and for HIV/HCV coinfected people. The FDA also said Harvoni plus ribavirin for 12 weeks is an alternative to a 24 weeks of Harvoni alone for treatment-experienced hepatitis C patients with liver cirrhosis.

Sofosbuvir, which was initially approved only for HCV genotype 1, has shown activity against these less common genotypes. It is not approved, however, for HCV genotypes 2 or 3. Sofosbuvir plus ribavirin alone is effective against genotype 2, and Gilead is working on a new coformulation with the pangenotypic NS5A inhibitor velpatasvir (formerly GS-5816) replacing ledipasvir.

The Phase 3 ION-4 trial showed that sofosbuvir/ledipasvir cured 96% of HIV/HCV coinfected people with HCV genotype 1 or 4 -- similar to sustained response rates seen in HCV monoinfected people. Good results from this and other studies of direct-acting antivirals have led experts to conclude that HIV/HCV coinfected people respond as well as HIV-negative individuals and are no longer a "special population" as they were in the interferon era.

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

Gilead U.S. FDA Approves New Indications for Harvoni, Gilead’s Once-Daily Single Tablet Regimen for Chronic Hepatitis C

-- Label Expanded to Include Patients with Genotypes 4, 5 and 6 and Patients Co-Infected with HIV

-- Use of Harvoni in Combination with Ribavirin for 12 Weeks Can be Considered for Treatment-Experienced Genotype 1 Patients with Cirrhosis

Foster City, Calif. -- November 12, 2015 -- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved Harvoni (ledipasvir/sofosbuvir) for expanded use in patients with genotype 4, 5 and 6 chronic hepatitis C virus (HCV) infection and in patients co-infected with HIV. In addition, Harvoni plus ribavirin (RBV) for 12 weeks was approved as an alternate therapy to 24 weeks of Harvoni for treatment-experienced, genotype 1 patients with cirrhosis. Harvoni received regulatory approval for the treatment of chronic HCV genotype 1 infection in adults in the United States in October 2014.

"Harvoni -- the first and only single-tablet regimen for the treatment of HCV -- continues to demonstrate high cure rates and a tolerable side effect profile across a range of patient populations, including those who have historically been considered among the most difficult to cure," said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. "We are pleased that the Harvoni label and prescribing information now includes guidance for health care providers on its use in these important HCV patient populations."

Genotypes 4, 5 and 6

The supplemental new drug application (sNDA) approval for HCV genotypes 4-6 was supported by data from the open-label trials 1119 and ELECTRON-2. Study 1119 evaluated Harvoni for 12 weeks in patients with HCV genotype 4 or 5 who were treatment-naive and treatment-experienced with or without cirrhosis. Results showed that 93 percent (41/44) of those with genotype 4 and 93 percent (38/41) of those with genotype 5 achieved SVR12. ELECTRON-2 evaluated Harvoni for 12 weeks in treatment-naive or previously-treated patients with genotype 6 HCV infection with or without cirrhosis. In this study, 96 percent (24/25) of patients achieved SVR12.

The most common adverse events (in at least 10 percent of subjects) were asthenia (18 percent), headache (14 percent) and fatigue (10 percent).

Patients Co-Infected with HIV

Patients with HCV/HIV co-infection represent approximately 30 percent of the total HIV-infected population in the United States. Compared with HCV infection alone, HIV/HCV co-infection is associated with an increased risk of cirrhosis and the subsequent complications of end-stage liver disease and hepatocellular carcinoma (liver cancer).

The sNDA approval for patients with HCV/HIV-1 co-infection was supported by data from the Phase 3 open-label ION-4 study, which evaluated Harvoni for 12 weeks for the treatment of genotypes 1 or 4 chronic HCV infection among patients co-infected with HIV. Data demonstrate that 96 percent (321/335) of patients achieved SVR12. The study included HCV treatment-naive (45 percent) and treatment-experienced (55 percent) patients, including patients with compensated cirrhosis (20 percent). The majority of patients were taking one of three HIV antiretroviral (ARV) regimens: tenofovir disoproxil fumarate (TDF) and emtricitabine with efavirenz (Atripla), raltegravir or rilpivirine (Complera).

The most common adverse events (in at least 10 percent of subjects) were headache (20 percent) and fatigue (17 percent).

Treatment-Experienced Patients with Cirrhosis

The sNDA approval of Harvoni with RBV for 12 weeks for genotype 1 treatment-experienced HCV patients with cirrhosis was supported by data from the Phase 2 SIRIUS study, which evaluated Harvoni plus RBV for 12 weeks or Harvoni without RBV for 24 weeks in genotype 1 HCV-infected patients with compensated cirrhosis who failed prior therapy. Ninety six percent (74/77) of patients treated with Harvoni plus RBV for 12 weeks, and 97 percent (75/77) of patients treated with Harvoni for 24 weeks without RBV, achieved SVR12.

The most common adverse reactions (occurring in at least 10 percent of subjects) among patients receiving Harvoni plus RBV for 12 weeks were asthenia (36 percent), headache (13 percent) and cough (11 percent). In patients receiving Harvoni for 24 weeks, these were asthenia (31 percent), headache (29 percent) and fatigue (18 percent).

The European Medicines Agency also recently approved updates to the Harvoni label to allow for the use of shorter durations of therapy with Harvoni in combination with RBV. Specifically, these include the use of Harvoni plus RBV for 12 weeks in genotypes 1 and 4 HCV-infected patients with compensated cirrhosis, decompensated cirrhosis and post-liver transplant patients. The new label also includes data further supporting use of Harvoni for 12 weeks in patients with genotypes 1 or 4 who are co-infected with HIV and in patients who had previously failed treatment with sofosbuvir plus RBV with or without pegylated interferon.

See full press release for important safety information for Harvoni

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

US full Prescribing Information for Atripla and Complera, including BOXED WARNING for both products, are also available at www.gilead.com.

11/19/15

Source

Gilead Sciences. U.S. FDA Approves New Indications for Harvoni, Gilead’s Once-Daily Single Tablet Regimen for Chronic Hepatitis C. Press release. November 12, 2015.