FDA approves Epclusa (sofosbuvir/velpatasvir) for chronic hepatitis C infection
Hepatitis C virus (HCV) causes inflammation of the liver; chronic hepatitis C infection can lead to many long-term complications, such as bleeding, jaundice, fluid accumulation, liver failure, cancer, and death. There are at least six known distinct hepatitis C genotypes: treatment strategies and their duration are dictated by these distinct strains.
In June, FDA approved EpclusaTM (sofosbuvir and velpatasvir, (SOF-VEL) for adults with chronic hepatitis C infection both with compensated cirrhosis or without cirrhosis as well as in combination with ribavirin for hepatitis C with decompensated cirrhosis. This medication contains a fixed-dose combination of sofosbuvir and velpatasvir. These drugs inhibit the replication of HCV and are the first FDA-approved treatment for all 6 genotypes of HCV.
Sofosbuvir is a nucleoside [nucleotide?] analog polymerase inhibitor, whereas velpatasvir inhibits the HCV protein NS5A. The efficacy of SOF-VEL was demonstrated in a series of phase 3 clinical trials known as the ASTRAL trials involving 1,035 patients infected with various genotypes of HCV.
ASTRAL-1 was a double-blind, placebo-controlled study involving untreated and previously treated patients with chronic HCV genotype 1, 2, 4, 5, or 6. Patients were randomized in a 5:1 ratio to receive a 12-week course of either SOF-VEL or placebo (n=624 treatment and n=116 placebo). The primary outcome was sustained virological response (SVR) 12 weeks after the end of therapy. Among recipients of 12 weeks of SOF-VEL, the SVR rate was 99% (95% confidence interval [CI], 98 to >99), which was significantly superior to the pre-specified performance goal of 85% (P<0.001). None of placebo recipients had a SVR and rates of SVR were similar regardless of HCV genotype.
Follow-up studies ASTRAL-2 and ASTRAL-3 were randomized open-label studies that compared once daily SOF-VEL with the combination of sofosbuvir and ribavirin (SOF-RIB), 1:1 randomization). ASTRAL-2 was done in patients with the HCV 2 genotype over 12 weeks. ASTRAL-3 was done in patients with the HCV 3 genotype over 24 weeks. The primary endpoint in both trials was SVR 12 weeks after therapy. Among patients with HCV genotype 2, the rate of SVR in the SOF-VEL group was 99%, which was superior to the 94% rate in the SOF-RIB group (P=0.02). Among patients with HCV genotype 3, the rate of SVR in the SOF-VEL group was 95%, which was superior to the 80% rate in the SOF-RIB group (P<0.001).