8-week sofosbuvir-velpatasvir-voxilaprevir for HCV as good as standard regimen
An 8-week regimen of sofosbuvir-velpatasvir-voxilaprevir combination is not noninferior to a 12-week regimen of sofosbuvir-velpatasvir for patients with chronic hepatitis C virus (HCV) infection, report two recent phase 3 open-label trials.
“In these international phase 3 trials, treatment with sofosbuvir-velpatasvir-voxilaprevir for 8 weeks resulted in high rates of [sustained viral response (SVR)] in HCV-infected patients with and without compensated cirrhosis,” the researchers said.
In one trial, the resulting SVR in the sofosbuvir-velpatasvir-voxilaprevir regimen was 95 percent, which “was not shown to be noninferior to that of 98 percent in patients receiving sofosbuvir-velpatasvir for 12 weeks,” they added.
The two phase 3 trials, POLARIS-2 and POLARIS-3, compared the efficacy of the 12-week sofosbuvir-velpatasvir with the 8-wek sofosbuvir-velpatasvir-voxilaprevir regimen. POLARIS-2 included patients of all HCV genotypes regardless of cirrhosis, while POLARIS-3 included only those with genotype 3 and with cirrhosis.
In POLARIS-2, 501 patients were assigned to the 8-week regimen while 440 were assigned to the 12-week regimen. The resulting SVRs were 95 percent (95 percent CI, 93 to 97 percent) and 98 percent (96 to 99 percent), respectively. [Gastroenterology 2017;153:113-122]
The SVRs corresponded to a 3.4-percent difference in the Mantel-Haenszel proportions between the groups, indicating that “8 weeks of sofosbuvir-velpatasvir-voxilaprevir did not meet the prespecified criteria for noninferiority to 12 weeks of sofosbuvir-velpatasvir,” explained researchers.
Four percent (n=21) of the patients who received the sofosbuvir-velpatasvir-voxilaprevir had virologic relapse. In contrast, only 1 percent (n=3) relapsed in the sofosbuvir-velpatasvir group. No cases of virologic breakthrough were reported.
“The difference in the efficacy was primarily due to the higher rate of relapse among patients with genotype 1a HCV infection receiving 8 weeks of sofosbuvir-velpatasvir-voxilaprevir,” explained researchers.
“Among patients receiving sofosbuvir-velpatasvir-voxilaprevir for 8 weeks with HCV genotypes other than genotype 1a, the rate of SVR was 97 percent,” they said.
In POLARIS-3, both groups showed an SVR rate of 96 percent (91 to 99 percent), which was significantly higher than the goal of 83 percent (p<0.001 for both). Two percent in the three-drug regimen had relapse, and 2 percent in the two-drug regimen had virologic failure.
“The lower rate of SVR among patients with HCV genotype 1a as compared to those with other genotypes receiving 8 weeks of sofosbuvir-velpatasvir-voxilaprevir was an unexpected finding. This difference was not observed in the phase 2 clinical trials,” researchers continued.
The findings show that, aside from HCV patients infected with 1a genotype, the 8-week sofosbuvir-velpatasvir-voxilaprevir regimen is a comparably effective and safe alternative to the 12-week regimen that excludes voxilaprevir.
This is important because the shorter treatment duration may be crucial in ensuring higher adherence which, according to the researchers, has become “the most important risk factor for treatment failure.”
“As the population of patients being treated for HCV expands from those engaged in healthcare systems to marginalized populations of homeless, incarcerated or those with addictions, the availability of a highly effective 8-week treatment regimen may enable more HCV-infected patients to be successfully treated with less burden on the resources of patients and providers,” they said.