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|Gilead Announces Sustained Virologic Response Rates from Two Phase 3 Studies of Sofosbuvir for Hepatitis C|
-- FISSION and NEUTRINO Studies Both Meet Primary Endpoints and Will Support Regulatory Filing for Sofosbuvir --
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 percent (170/253) of patients achieving a sustained virologic response (SVR) in the sofosbuvir plus RBV treatment group versus 67 percent (162/243) in the peg-IFN plus RBV treatment group (95 percent CI for the difference: -7.5 to +8.0 percent for sofosbuvir plus RBV versus peg-IFN plus RBV; predefined criterion for non-inferiority was a lower bound of a two sided 95 percent CI of -15 percent). All common adverse events (≥10 percent 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 percent 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 percent with 90 percent (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 anemia.
“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
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 percent of patients had compensated cirrhosis (advanced liver disease) and 72 percent had genotype 3 infection. The SVR12 rates in patients receiving sofosbuvir plus RBV were 97 percent for genotype 2 patients and 56 percent for genotype 3 patients. The SVR12 rates in patients receiving peg-IFN plus RBV in this study were 78 percent for genotype 2 patients and 63 percent for genotype 3 patients. Among patients with cirrhosis at baseline who received sofosbuvir/RBV, 47 percent achieved SVR12; 38 percent 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 (1 percent) receiving sofosbuvir discontinued treatment due to adverse events compared to 26 patients (11 percent) 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 percent of patients had compensated cirrhosis and 89 percent were infected with genotype 1. Among genotype 1 patients, 89 percent achieved SVR12. Of the 35 patients with genotypes 4, 5 or 6, 97 percent achieved SVR12. Among patients with cirrhosis at baseline, 80 percent 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 3 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.
Additional information about these and other ongoing clinical studies can be found at www.clinicaltrials.gov. Sofosbuvir is an investigational product and its safety and efficacy have not yet been established.
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 that the proportion of patients in the FISSION and NEUTRINO
trials will not maintain SVR with longer follow up as favorable as the
SVR12 rates reported in this press release. In addition, there is the
possibility of unfavorable results from additional clinical trials
involving sofosbuvir, including the FUSION trial. Further, we may not
release topline results from the FUSION study or file for regulatory
approval of sofosbuvir in the timelines currently contemplated. As a
result, sofosbuvir may never be successfully commercialized. Further,
Gilead may make a strategic decision to discontinue development of the
compound if, for example, Gilead believes commercialization will be
difficult relative to other opportunities in its pipeline. 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 Quarterly
Report on Form 10-Q for the quarter ended
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