Research in context
Evidence before this study
Before the approval of sofosbuvir–velpatasvir–voxilaprevir, no retreatment options were approved for patients with chronic hepatitis C virus infection who had been treated with a direct-acting antiviral regimen containing an NS5A inhibitor. The POLARIS-1 study was the first phase 3 registrational, randomised, placebo-controlled trial to enrol and treat such patients, as we confirmed by a review of PubMed using the search terms, “HCV”, “NS5A treatment-experienced”, “prior DAA experience”, and “salvage therapy”, for clinical trials published by Aug 21, 2015. In the primary study of POLARIS-1, 253 (96%) of 263 patients who received sofosbuvir–velpatasvir–voxilaprevir for 12 weeks achieved sustained virological response.
Added value of this study
In the current substudy of POLARIS-1, patients with genotype 1 hepatitis C virus infection assigned to the placebo group in the primary study of POLARIS-1 were subsequently treated with sofosbuvir–velpatasvir–voxilaprevir for 12 weeks to assess efficacy and safety. The large number of patients (143 [97%] of 147) treated in this deferred treatment substudy who achieved sustained virological response further supports the efficacy and safety of treatment in the primary study. Combined with the results of the primary study of POLARIS-1, 396 (97%) of 410 patients have achieved sustained virological response in clinical trials with sofosbuvir–velpatasvir–voxilaprevir.
Implications of all the available evidence
These results support the use of sofosbuvir–velpatasvir–voxilaprevir for the treatment of chronic hepatitis C virus infection in patients with NS5A inhibitor experience, regardless of which direct-acting antivirals were used in previous treatments.