Fixed-dose combination of velpatasvir and sofosbuvir produced high rates of 12-week sustained virologic response in patients with HCV genotypes 1 through 6.
Drug maker Gilead Sciences announced that its investigational drug paired with the blockbuster drug Sovaldi scored high cure rates with six genotypes of the hepatitis C virus in late-phase clinical trials for treatment of the disease.
The company released topline results for four international phase 3 clinical studies, dubbed ASTRAL, that tested a once-daily, fixed-dose combination of velpatasvir (VEL), an investigational drug and sofosbuvir (SOF), marketed by Gilead as Sovaldi. Velpatasvir is being developed by the company as a pangenotypic NS5A inhibitor for the treatment of chronic hepatitis C infection for patients with genotypes 1 through 6 of the virus, according to the company statement.
“The ASTRAL study results demonstrate that a 12-week course of therapy with the first fixed-dose combination of two pan-genotypic compounds can provide high cure rates for patients with all HCV (hepatitis C virus) genotypes,” said Norbert Bischofberger, PhD, Gilead’s executive vice president of research and development and chief scientific officer. “We are pleased to have now brought forward our second single tablet regimen for HCV infection that complements Harvoni, our first single tablet regimen approved specifically for patients with genotype 1 infection and which could eliminate the need for HCV genotype testing. We look forward to advancing the regulatory submissions for the SOF/VEL fixed-dose combination.”
The primary efficacy endpoint for all four studies was for patients to achieve sustained virologic response (SVR) at 12 weeks after they completed treatment, an indication that the patient is cured because the virus is no longer detectable in the blood.
The main endpoint was achieved by 98% of patients in three trials, the release states. There were 20 patients who did not meet the endpoint and of those 13 experienced virologic failure and seven were lost to follow-up and did not complete the SVR12 visit, the release states.
There were a total of 1035 patients in ASTRAL trials 1, 2 and 3 who were given SOF/VEL for 12 weeks to treat hepatitis C infection, including genotypes 1 through 6. Among those patients, 21% had compensated cirrhosis and 28% had not been cured in previous hepatitis C treatment attempts, according to the release.
Patients from all three studies who were given SOF/VEL had similar adverse events to those who were given placebo in the ASTRAL-1 study and two patients stopped taking the drug due to adverse events. The most common side effects were headache, fatigue and nausea, according to the release.
There were nine deaths among the 18% of patients who experienced treatment-emergent serious adverse events (SAEs), the release states. Gilead said the deaths were associated with advanced liver disease, as was the majority of the (SAEs), and were not related to the study drug.
In ASTRAL 4, the fourth trial, patients with decompensated cirrhosis who were given ribavirin along with SOF/VEL for 12 weeks achieved higher SVR12 rates (94%) than those who were given SOF/VEL for either 12 or 24 weeks (83% and 86% respectively). The most common adverse events among the 264 patients in this study were fatigue, nausea and headache, the release states.
Gilead’s latest hepatitis C investigational drug, SOF/VEL, has been granted breakthrough therapy status by the FDA, which could help hasten the path to approval. The company said it plans to file a drug approval application with the agency and European drug authorities by the end of 2015.