Gilead Sciences, a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need, has reported topline results from two phase III studies, FISSION and NEUTRINO, evaluating a 12-week course of the once-daily nucleotide sofosbuvir in combination with ribavirin (FISSION) and in combination with ribavirin and pegylated interferon (NEUTRINO) among treatment-naïve patients with chronic hepatitis C virus (HCV) infection.

In the FISSION study, patients with genotype 2 or 3 HCV infection were randomized to receive either a 12-week course of sofosbuvir plus ribavirin (RBV) or standard of care with 24 weeks of pegylated interferon alfa-2a (peg-IFN) plus RBV. The study met its primary efficacy endpoint of non-inferiority of sofosbuvir plus RBV to peg-IFN plus RBV, with 67 per cent (170/253) of patients achieving a sustained virologic response (SVR) in the sofosbuvir plus RBV treatment group versus 67 per cent (162/243) in the peg-IFN plus RBV treatment group (95 per cent CI for the difference: -7.5 to +8.0 per cent for sofosbuvir plus RBV versus peg-IFN plus RBV; predefined criterion for non-inferiority was a lower bound of a two sided 95 per cent CI of -15 per cent). All common adverse events (=10 per cent in any group) occurred more frequently in subjects receiving peg-IFN and RBV as compared to sofosbuvir and RBV. The most common adverse events in the sofosbuvir plus RBV arm occurring in =10 per cent of the patients were fatigue, headache, nausea, insomnia and dizziness.

In the NEUTRINO study, patients with genotype 1, 4, 5 or 6 HCV infection were treated with a 12-week course of sofosbuvir, RBV and peg-IFN. This study met its primary efficacy endpoint of superiority compared to a predefined historic control SVR rate of 60 per cent with 90 per cent (295/327) of patients achieving SVR12 after completing therapy (P<0.001).

In the NEUTRINO study the most common adverse events that occurred in =20 percent of patients were fatigue, headache, nausea, insomnia and anaemia.

"These data support the favorable clinical profile of sofosbuvir as the backbone of a potent, safe and well-tolerated treatment regimen that is effective across a broad range of HCV patient genotypes," said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. "The sofosbuvir regimens in these trials allowed us to shorten the duration of effective hepatitis C therapy to just 12 weeks for treatment-naïve patients with genotypes 1 through 6."

In FISSION, treatment-naïve HCV genotype 2 and 3 patients were randomized (1:1) to receive either 12 weeks of sofosbuvir 400 mg once daily plus RBV (1,000 or 1,200 mg/day) (n=256) or 24 weeks of peg-IFN (180 µg/week) plus RBV (800 mg/day) (n=243). Overall, 20 per cent of patients had compensated cirrhosis (advanced liver disease) and 72 per cent had genotype 3 infection. The SVR12 rates in patients receiving sofosbuvir plus RBV were 97 per cent for genotype 2 patients and 56 per cent for genotype 3 patients. The SVR12 rates in patients receiving peg-IFN plus RBV in this study were 78 per cent for genotype 2 patients and 63 per cent for genotype 3 patients. Among patients with cirrhosis at baseline who received sofosbuvir/RBV, 47 per cent achieved SVR12; 38 per cent of cirrhotics who received peg-IFN plus RBV achieved SVR12.

With the exception of one patient who was non-compliant, all patients in the sofosbuvir/RBV arm became HCV negative on treatment and relapse accounted for the virologic failures.

Three patients (one per cent) receiving sofosbuvir discontinued treatment due to adverse events compared to 26 patients (11 per cent) receiving peg-IFN/RBV.

In NEUTRINO, 327 treatment-naïve HCV genotype 1, 4, 5 and 6 patients were treated for 12 weeks with sofosbuvir 400 mg once daily in combination with RBV (1,000 or 1,200 mg/day) and peg-IFN (180 µg/week). Seventeen per cent of patients had compensated cirrhosis and 89 per cent were infected with genotype 1. Among genotype 1 patients, 89 per cent achieved SVR12. Of the 35 patients with genotypes 4, 5 or 6, 97 per cent achieved SVR12. Among patients with cirrhosis at baseline, 80 per cent achieved SVR12. All patients in this study became HCV RNA negative on treatment and relapse accounted for all virologic failures.

Five patients (2 percent) receiving sofosbuvir in combination with peg-IFN and RBV discontinued treatment due to adverse events.

FISSION, NEUTRINO, POSITRON and FUSION are the pivotal phase III studies designed to support an initial regulatory filing for sofosbuvir as part of all-oral therapy with RBV for genotype 2 and 3 treatment-naïve, treatment-experienced and interferon-intolerant HCV patients, and for sofosbuvir in combination with RBV and peg-IFN for genotype 1, 4, 5 and 6 treatment-naïve patients. Topline results from the POSITRON study were announced in November 2012, and topline results from the last Phase 3 study, FUSION, are anticipated later this quarter. Full results from all four studies will be presented at a future scientific conference.