Top-line results from four global Phase 3 clinical studies (POLARIS-1, POLARIS-2, POLARIS-3, and POLARIS-4), led by Gilead Sciences, showed that the combination of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) — inhibitors of viral activity — can effectively treat chronic hepatitis C virus (HCV) infection.
Data will be presented at The Liver Meeting 2016, set for Nov. 11–15 in Boston, and Gilead plans to soon file for regulatory approval of the treatment in the U.S.
In all four studies, SOF/VEL/VOX treatment was given in a once-daily, fixed-dose combination. Their primary endpoint was the sustained virologic response (SVR) at 12 weeks after the discontinuation of therapy (SVR12), which assesses the decline in viral activity.
POLARIS-1 (NCT02607735) and POLARIS-4 (NCT02639247) followed 445 patients infected with HCV types 1-6, who had been previously treated with direct-acting antiviral agents (DAAs). After 12 weeks of treatment, these patients showed an SVR12 rate of 96 percent (POLARIS-1) and 97 percent (POLARIS-4), versus 0 percent in the placebo group.
POLARIS-2 (NCT02607800) and POLARIS-3 (NCT02639338) included 611 patients who had never received DAA treatment. The POLARIS-2 study enrolled patients with HCV types 1-6, with or without compensated cirrhosis (also referred to as early cirrhosis, a condition characterized by fibrosis in the liver tissue), whereas the POLARIS-3 followed patients with HCV type 3 and compensated cirrhosis. All patients received eight weeks of SOF/VEL/VOX. The results indicated that 95 percent (POLARIS-2) and 96 percent (POLARIS-3) of the treated patients achieved SVR12.
People treated with SOF/VEL/VOX for either 12 or eight weeks experienced similar adverse events, which included headache, fatigue, diarrhea and nausea. Among the 1,056 people given SOF/VEL/VOX in the studies, only one patient discontinued treatment due to an adverse event.
“Despite recent advances that have provided high cure rates and simplified treatment for most HCV patients, those who have failed previous treatment with direct acting antivirals continue to represent an unmet medical need,” Norbert Bischofberger, PhD, executive vice president of Research and Development and chief scientific officer at Gilead, said in a news release. “The POLARIS study results demonstrate that combining three potent antivirals with different mechanisms of action and high barriers to resistance can provide high cure rates for patients who have failed other highly effective oral DAA regimens.”
“Based on these Phase 3 results, we plan to submit regulatory applications for SOF/VEL/VOX for the treatment of chronic HCV in the United States in the fourth quarter of 2016 and shortly thereafter in Europe.”
The SOF/VEL/VOX fixed-dose combination was previously designated a Breakthrough Therapy by the U.S. Food and Drug Administration (FDA) for the treatment of patients with chronic type 1 HCV infection in patients who failed to respond to other therapies.