Gilead Sciences appears poised to continue dominating the hepatitis C virus (HCV) treatment market as the company releases excellent results from several large studies of a new regimen that treats all genotypes of the virus. Gilead released top-line results from four international Phase III clinical trials, ASTRAL-1, -2, -3 and -4, investigating a once-daily, fixed-dose combination of the nucleotide analog polymerase inhibitor Sovaldi (sofosbuvir) and the investigational pangenotypic NS5A inhibitor velpatasvir for the treatment of genotypes 1 through 6 of hep C.

The ASTRAL-1, -2 and -3 studies included 1,035 people with genotypes 1 through 6 of hep C, who were treated with Sovaldi/velpatasvir for 12 weeks. Twenty-one percent of the participants had compensated cirrhosis and 28 percent had failed a previous cure attempt. The participants were randomized to take Sovaldi/velpatasvir or a placebo for 12 weeks. ASTRAL-1 in particular was a double-blind, placebo-controlled trial including 740 participants with all genotypes except 3.

The ASTRAL-4 study included 267 individuals of all genotypes, all of whom had decompensated cirrhosis. They were randomized to take 12 weeks of Sovaldi/velpatasvir with or without ribavirin, or to take 24 weeks of just Sovaldi/velpatasvir.

In most cases, when breaking down the results according to ribavirin use, treatment length and genotype, the regimens led to rates of sustained virologic response 12 weeks after completing therapy (SVR12, considered a cure) of 94 percent to 100 percent. These results are comparable to the cure rates seen in Phase III trials of Gilead’s current hep C blockbuster regimen, Harvoni (ledipasvir/sofosbuvir), among those with genotype 1 of the virus.

Participants with decompensated cirrhosis experienced lower cure rates. In ASTRAL-4, 83 percent (75 of 90 participants) of those who took Sovaldi/velpatasvir for 12 weeks were cured, as were 86 percent (77 of 90) of those who took the regimen for 24 weeks. Using ribavirin in addition to the single-tablet regimen resulted in a 94 percent cure rate (82 of 97) among those treated for 12 weeks. Looking just at those with genotype 1 and 3 who were treated with the ribavirin-inclusive regimen for 12 weeks, the cure rates were a respective 96 percent and 85 percent.

In ASTRAL-3, 95 percent (264 of 277) of those with genotype 3 were cured after 12 weeks of Sovaldi/velpatasvir. Since the respective approvals of Gilead’s Sovaldi (sofosbuvir) and Harvoni made the once-difficult-to-treat genotype 1 easier to cure, genotype 3 has assumed the title of the hardest to cure genotype.

Those who were treated with Sovaldi/velpatasvir for 12 weeks in the first three ASTRAL studies experienced similar adverse side effects compared with those who received the placebo in ASTRAL-2. Two participants (0.2 percent) who took the regimen for 12 weeks (one from each of the first two ASTRAL trials) stopped treatment because of side effects. The most common side effects were headache, fatigue and nausea.

IN ASTRAL-4, the most common side effects in all the arms were fatigue, nausea and headache. Anemia occurred among 31 percent of those taking ribavirin, and in 4 percent and 3 percent of those taking the hep C regimen without ribavirin for a respective 12 and 24 weeks. Eighteen percent of the participants experienced serious adverse health conditions. (Again, this study included only those with decompensated cirrhosis, the more advanced state of cirrhosis.) Nine participants died. Most of the serious adverse health conditions and deaths were linked to advanced liver disease.

To read a press release about the study, click here.