Gilead Sciences, Inc., a biopharmaceutical company, announced that the US 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, Ph.D., 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."

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-naïve and treatment-experienced patients with genotype 1 and 4 infection who had undergone liver transplantation and/or who had decompensated liver disease.

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

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).

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 per cent and 2 per cent of patients discontinued Harvoni with RBV due to an adverse event, respectively. The most common adverse reactions (=10 per cent, all grades) observed with treatment with Harvoni in combination with RBV for 12 weeks were asthenia, headache and cough.

Most common (=10 per cent, all grades) adverse reactions were fatigue, headache and asthenia.