A single-pill regimen successfully treated hepatitis C virus (HCV) in patients who had previously not responded to treatment, according to a recent industry-funded study.
The study included two phase 3 trials. All patients had chronic HCV and had been previously treated with direct-acting antiviral agents without sustained virologic response. In the first trial, called POLARIS-1, patients had previously taken a regimen containing an NS5A inhibitor. Three hundred such patients with HCV genotype 1 were randomly assigned to placebo or combination treatment with the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir once daily for 12 weeks. Patients with other HCV genotypes were all given the combination therapy.
The other trial, called POLARIS-4, included patients who had previously received a direct-acting antiviral agent regimen that did not include an NS5A inhibitor. The 314 patients who had HCV genotype 1, 2, or 3 were randomized to either sofosbuvir-velpatasvir-voxilaprevir or sofosbuvir-velpatasvir for 12 weeks. An additional 19 patients with HCV genotype 4 infection were assigned to the three-drug combination. When POLARIS-1 and POLARIS-4 were combined, 46% of the patients in the active treatment groups were found to have compensated cirrhosis. The study was published in the June 1 New England Journal of Medicine and funded by Gilead Sciences.
The results of POLARIS-1 showed sustained virologic response in 96% of patients treated with sofosbuvir-velpatasvir-voxilaprevir, compared to 0% with placebo. In POLARIS-4, the response rate was 98% with sofosbuvir-velpatasvir-voxilaprevir and 90% with sofosbuvir-velpatasvir. The most common adverse events were headache, fatigue, diarrhea, and nausea, and 1% or less of patients receiving the active medications discontinued treatment due to adverse events.
The study authors concluded that the three-drug regimen was highly effective for patients with HCV of any genotype, with or without compensated cirrhosis, who did not respond to previous treatment with direct-acting antiviral agents. “This population has been underrepresented in clinical trials and has limited retreatment options,” they noted. The study only included those who completed their previous treatments, not patients who were nonadherent or discontinued due to adverse events, they cautioned.
Other limitations that restrict the generalizability of the results include the small numbers of patients with genotype 3 infection and cirrhosis, with rarer HCV genotypes, and previously treated with newer HCV regimens that included velpatasvir or elbasvir. The authors also noted that patients were excluded from the trials if they were co-infected with hepatitis B virus or HIV or had decompensated cirrhosis.