Evaluation of sofosbuvir, velpatasvir plus voxilaprevir as fixed-dose co-formulation for treating hepatitis C

Abstract

The fixed-dose combination of three direct-acting antivirals (DAA), namely sofosbuvir, velpatasvir and voxilaprevir is the first pangenotypic, single tablet regimen developed for the treatment of HCV infection. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy and safety of the co-formulation are reviewed. Information on drug absorption, distribution, metabolism and excretion of each of the three antivirals is evaluated. Finally, antiviral activity, safety and potential for drug interactions in phase II/III clinical trials in distinct patient populations are discussed. Expert opinion: The triple co-formulation of sofosbuvir-velpatasvir-voxilaprevir represents a major step towards HCV eradication. It depicts high efficacy even in patients infected with viruses harboring resistance-associated substitutions (RAS), including those selected after DAA failures. Likewise, very high success rates and good tolerance are seen in special patient populations, including decompensated cirrhotics, HIV coinfection, organ transplantation or renal insufficiency. A pill once daily for 8 weeks gives SVR rates above 95%. In prior DAA failures, extending treatment to 12 weeks maximizes SVR rates.

Keywords: Fixed-dose combinations; co-formulations; drug interactions; drug resistance; pharmacokinetics; single tablet regimen; velpatasvir; voxilaprevir.