Gilead Sciences, Inc. announced results from four international phase 3 clinical trials, ASTRAL-1, ASTRAL-2, ASTRAL-3 and ASTRAL-4, which showed that Sovaldi in combination with velpatasvir, an investigational pangenotypic NS5A inhibitor, produced high sustained virologic response rates in patients with hepatitis C virus infection.
In the ASTRAL-1, ASTRAL-2, and ASTRAL-3 studies, 1,035 patients with HCV genotype 1 to 6 were assigned a dosage of Sovaldi (sofosbuvir, Gilead Sciences) and velpatasvir (Gilead Sciences) for 12 weeks. Of these patients, 21% had compensated cirrhosis and 28% failed prior treatments. In the ASTRAL-4 study, 267 patients with decompensated cirrhosis were randomly assigned to a regimen of sofosbuvir and velpatasvir with or without ribavirin for 12 weeks, or sofosbuvir and velpatasvir for 24 weeks.
Of the patients in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 98% achieved SVR12 (n = 1,015). Of the 20 patients who did not achieve SVR12, 13 patients experienced virologic failure and seven were lost to follow-up. Twelve of the 13 virologic failure patients relapsed and no patients with genotype 2, 4, 5 or 6 HCV infection had virologic failure. The most common adverse events were headache, fatigue and nausea. Two patients, one each in ASTRAL-1 and ASTRAL-2, discontinued treatment due to adverse events, according to the release.
In the ASTRAL-4 trial, more patients with decompensated cirrhosis who received the combination regimen with ribavirin achieved SVR12 compared with other patients treated with just the combination regimen. The release stated that patients with HCV genotype 1 and 3 treated with the combination regimen with ribavirin had SVR12 rates of 96% and 85%, respectively.
The most common adverse events in ASTRAL-4 were fatigue, nausea and headache. Treatment-related serious adverse events were observed in 18% of patients and nine patients died. “The majority of serious adverse events and deaths were associated with advanced liver disease,” according to the release.
“The ASTRAL study results demonstrate that a 12-week course of therapy with the first fixed-dose combination of two pangenotypic compounds can provide high cure rates for patients with all HCV genotypes,” Norbert Bischofberger, PhD, chief scientific officer at Gilead, said in the release. “We are pleased to have now brought forward our second single-tablet regimen for HCV infection that complements Harvoni [ledipasvir/sofosbuvir], our first single-tablet regimen approved specifically for patients with genotype 1 infection, and which could eliminate the need for HCV genotype testing.”
According to the release, the FDA assigned breakthrough therapy designation to Gilead for the combination of sofosbuvir and velpatasvir.
Disclosures: Bischofberger reports being employed by Gilead Sciences.