Gilead submits NDA for Sovaldi/velpatasvir in all HCV genotypes

Gilead Sciences announced it has submitted a new drug application to the FDA for a fixed combination of Sovaldi and velpatasvir, an investigational inhibitor, for the treatment of all genotypes of chronic hepatitis C virus infection.

The application was submitted after results from multiple phase 3 ASTRAL trials yielded high sustained virologic response rates after investigating the safety and efficacy of a fixed-dose combination of Sovaldi (sofosbuvir, Gilead Sciences) and velpatasvir (Gilead Sciences), a pan-genotypic NS5A inhibitor, among patients with HCV genotypes 1 through 6.

“As the first fixed-dose combination of two pan-genotypic, direct-acting antivirals, [sofosbuvir/velpatasvir] represents an important step forward in the treatment of patients with hepatitis C,” Norbert Bischofberger, PhD, executive vice president, research and development, and chief scientific officer at Gilead, said in a press release. “Genotype 1 is the most prevalent form of HCV in the United States, but worldwide, more than half of people living with HCV are infected with other genotypes.”

In the ASTRAL-1, ASTRAL-2 and ASTRAL-3 trials, 1,035 patients underwent therapy with the fixed combination regimen for 12 weeks. Of these patients, 98% achieved SVR at 12 weeks (1,015). In the ASTRAL-4 trial, 267 patients with decompensated cirrhosis were randomly assigned to receive either sofosbuvir/velpatasvir with or without ribavirin for 12 weeks or 24 weeks of sofosbuvir/velpatasvir. Ninety-four percent of patients who received sofosbuvir/velpatasvir plus ribavirin for 12 weeks achieved SVR12, whereas 83% of patients who received sofosbuvir/velpatasvir for 12 weeks achieved SVR12 and 86% of patients who received sofosbuvir/velpatasvir for 24 weeks achieved SVR.

The release further stated that adverse events were similar among patients treated with sofosbuvir/velpatasvir for 12 weeks from the ASTRAL-1, -2 and -3 trials compared with patients treated with placebo in ASTRAL-1. The most common adverse events were headache, fatigue and nausea. The most common adverse events in ASTRAL-4 were the same.

A previous press release stated that treatment-related serious adverse events were observed in 18% of patients in ASTRAL-4 and nine patients died. “The majority of serious adverse events and deaths were associated with advanced liver disease,” according to the release.

The FDA assigned breakthrough therapy designation to Gilead for the combination of sofosbuvir and velpatasvir, according to the release.

Disclosures: Bischofberger is employed by Gilead.