Gilead Seeking FDA Approval for Pan-Genotype Hepatitis C Drug

Gilead Sciences recently filed a New Drug Application with the US Food and Drug Administration for a single-tablet regimen to treat chronic infection of all forms of the hepatitis C virus.

In a move that could make it the leader of the pack among pharmaceutical companies with the first pan-genotypic drug for hepatitis C, Gilead Sciences filed a New Drug Application with the US Food and Drug Administration for a single-tablet regimen to treat chronic infection of the virus.

Researchers have found that the liver-damaging hepatitis C virus has a high degree of genetic diversity characterized by regional variations in genotype prevalence. While the most common of the six strains is genotype 1, there are five other strains and yet no single drug currently approved to treat all genotypes.

The California-based Gilead announced last week that it submitted the NDA for a once-daily-fixed dose combination of the nucleotide analog polymerase inhibitor Sovaldi, known generically as sofosbuvir (SOF), and velpatasvir (VEL), an investigational pan-genotypic NS5A inhibitor to treat chronic infection of genotypes 1 through 6 of the hepatitis C virus (HCV).

Sovaldi was approved by the FDA nearly two years ago and velpatasvir is a drug that is under development by Gilead and has not received regulatory approval. The pharmaceutical company Merck is also working to develop a one pill drug that could potentially treat all six genotypes of HCV.

Gilead said its FDA application contains data results from clinical trials that studied use of 12 weeks of SOF/VEL in patients with chronic infection of HCV genotype 1 through 6. The trials included patients with compensated cirrhosis, as well as patients with decompensated cirrhosis whose treatment also included ribavirin, according to a release from Gilead that announced the regulatory filing.

“As the first fixed-dose combination of two pan-genotypic, direct-acting antivirals, SOF/VEL represents an important step forward in the treatment of patients with hepatitis C,” Norbert Bischofberger, PhD, Gilead’s executive vice president of research and development and chief scientific officer, stated in the 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,” Bischofberger said. “SOF/VEL complements our current HCV portfolio of Sovaldi and Harvoni, offering high cure rates and the potential to simplify treatment and eliminate the need for HCV genotype testing.”

The NDA is based on data from Gilead’s four international phase 3 studies dubbed the ASTRAL trials. The primary efficacy endpoint for all four studies was for patients to achieve sustained virologic response (SVR) at 12 weeks after they completed treatment, which indicates that the patient is cured and the virus is no longer detectable in the blood.

The main endpoint was achieved by 98% of the 1035 patients in ASTRAL trials 1, 2, and 3, according to the release. Cure rates of 267 patients with decompensated cirrhosis in ASTRAL-4 trial were 94% among those who took SOF/VEL plus ribavirin for 12 weeks, and ranged from 83% (12 weeks) to 86% (24 weeks) among patients who took only SOF/VEL, the release states.

The most common adverse events were headache, fatigue and nausea and were similar to those experienced by patients who took placebo, according to the release. Gilead said in topline results it released in September that there were nine deaths among the 18% of patients who experienced treatment-emergent serious adverse events (SAEs). The company said that the deaths were associated with advanced liver disease, as was the majority of the (SAEs), and were not related to the study drug.

The FDA has granted SOF/VEL a Breakthrough Therapy designation assigned to drugs that could provide major advances in treatment of a disease, according to the release. Gilead also plans to seek regulatory approval for the same drug with the European Union by year’s end.