Regulatory Decision Summary for Vosevi

Health Canada considers that the benefit/risk profile of Vosevi is favourable when used as directed in the treatment of chronic hepatitis C virus infection in adult patients, with or without compensated cirrhosis, who have (a) genotype 1, 2, 3, 4, 5 or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor or (b) genotype 1, 2, 3 or 4 have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor.

Vosevi is a fixed-dose, combination tablet containing sofosbuvir, velpatasvir and voxilaprevir. Treatment recommendations for Vosevi are based on viral genotype and prior treatment history.

The indication is based on the results of two Phase III clinical trials supporting the efficacy and safety of Vosevi in adult patients with chronic HCV infection, with or without compensated cirrhosis, who have failed prior therapy with an HCV regimen containing an NS5A inhibitor, or who have failed prior treatment with an HCV regimen containing sofosbuvir without an NS5A inhibitor.

The primary efficacy and safety data supporting this indication are derived from two Phase III randomized multicenter clinical trial studies. One randomized, multicenter, placebo-controlled study was conducted in patients who had failed prior therapy with an NS5A inhibitor. The second clinical trial used sofosbuvir/velpatasvir as an active comparator in patients who had failed prior therapy with sofosbuvir without an NS5A inhibitor. Data from these clinical studies have provided the evidence of efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir single-tablet regimen in adult patients without cirrhosis or with compensated cirrhosis, who have (a) genotype 1, 2, 3, 4, 5 or 6 infection and have previously been treated with an HCV regimen containing an NS5A inhibitor or (b) genotype 1, 2, 3 or 4 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor. Health Canada considers that the benefit/risk profile of Vosevi is favourable when used as directed.

Vosevi was assessed by measuring the sustained virologic response rates (SVR12) at follow-up Week 12. Sustained antiviral response and high cure rates were noted. The SVR12 rate in NS5A inhibitor-experienced patients with chronic HCV genotypes 1 to 6 infection with compensated cirrhosis or with cirrhosis was 96%. The SVR12 rate in non-NS5A inhibitor-experienced patients with chronic HCV genotypes 1 to 4 infection with compensated cirrhosis or with cirrhosis was 98%, whereas the active comparator (sofosbuvir/velpatasvir) treatment arm patients had an SVR12 rate of 90%.

Vosevi was found to be safe. No significant serious adverse events or early discontinuations due to adverse events were noted. The adverse events profile was similar to the one reported in adults, with the most common being headache (22%), fatigue (18%), diarrhea (13%) and nausea (12%). The most common Grade 3 or 4 laboratory abnormalities that occurred in >2% of subject were hyperbilirubinemia, hyperglycemia (all occurring in patients with diabetes mellitus), increased lipase, and decreased platelets.

The safety and efficacy of Vosevi has been established and can be used for the treatment of chronic hepatitis C virus infection in adult patients, without cirrhosis or with compensated cirrhosis, who have (1) genotype 1, 2, 3, 4, 5 or 6 infection and have previously been treated with an HCV treatment regimen containing an NS5A inhibitor or (2) genotype 1, 2, 3 or 4 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor.

Based on the data submitted, Health Canada considers that the anticipated benefits of Vosevi outweigh the potential risks under the conditions of use described in the Vosevi Product Monograph at this time.