Sofosbuvir-velpatasvir: A single-tablet treatment for hepatitis C infection of all genotypes

The pharmacology, pharmacokinetics, interaction potential, efficacy, and safety of the newest direct-acting antiviral (DAA) medication for the treatment of chronic hepatitis C are reviewed.

Nonstructural proteins 5A (NS5A) and 5B (NS5B) are key drivers of hepatitis C virus (HCV) replication. Velpatasvir, an inhibitor of NS5A, was coformulated with the NS5B inhibitor sofosbuvir to provide a single-tablet combination DAA (Epclusa, Gilead Sciences). Sofosbuvir-velpatasvir was shown to have excellent activity against the 6 most prevalent HCV genotypes in the United States, with reported rates of sustained virological response at 12 weeks after treatment completion ranging from 95% to 100% in various HCV-infected populations, including patients with compensated cirrhosis and prior treatment failures. In patients with decompensated cirrhosis or HIV coinfection, reported cure rates are 85-100% and 92-100%, respectively. The duration of treatment with sofosbuvir-velpatasvir is 12 weeks regardless of the HCV genotype involved, previous treatment, and the presence of cirrhosis or baseline resistance-associated NS5A mutations. In patients with decompensated cirrhosis, sofosbuvir-velpatasvir must be used in combination with ribavirin. Sofosbuvir-velpatasvir was well tolerated in clinical trials; adverse effects reported at a rate of ≥10% were fatigue, headache, nausea, and nasopharyngitis.

Sofosbuvir-velpatasvir is a DAA and the first single-tablet regimen to treat HCV infection caused by all genotypes. The efficacy and tolerability of sofosbuvir-velpatasvir have been observed in patients with types of HCV infection that traditionally have been difficult to treat.