Regulatory Decision Summary for Maviret

The purpose of this Supplement to a New Drug Submission (SNDS) was to expand the indication of Maviret to treatment of acute hepatitis C virus (HCV) infection in adults and pediatric participants 3 years of age and older and weighing ≥ 12 kg. Upon review, this indication was acceptable.

This submission was filed and reviewed under the Priority Review Policy.

The efficacy and safety of Maviret in participants with documented acute hepatitis C virus (HCV) infection was evaluated in Study M20-350, a single-arm, open-label clinical trial of 286 adults who were treatment-naïve for the current infection and who received Maviret once daily for eight weeks. The diagnosis of acute HCV infection at screening was based on physician diagnosis, quantifiable HCV RNA, and one or more of the following criteria: a negative anti-HCV antibody, HCV RNA or HCV core antigen testing result followed by positive HCV RNA or HCV core antigen testing, clinical signs of liver disease associated with acute HCV infection, and recent risk behaviours associated with HCV transmission. Eighty-four percent of enrolled subjects had evidence of clinical hepatitis at screening in the absence of other causes of liver disease, recent risk behavior for HCV transmission, and a confirmed HCV RNA or HCV core antigen positivity within 8 months prior to screening. At baseline, 96% of subjects had quantifiable HCV RNA, of whom 39% had a documented result of negative HCV antibody or unquantifiable HCV RNA within the previous year, and 4% of subjects had unquantifiable HCV RNA possibly reflecting spontaneous clearance of the HCV infection during the pre-treatment period. Eligible participants had no cirrhosis or had compensated cirrhosis and were required to have no evidence of chronic HCV or hepatitis B infection.

The median age of study participants was 43 years (range: 20 to 78); 82% had no history of a prior HCV infection; 64% were HCV genotype 1, 4% were HCV genotype 2, 13% were HCV genotype 3, 19% were HCV genotype 4; 6% were ≥ 65 years; 89% were male; 11% were Black; 2% had cirrhosis; 50% had HIV co-infection; 14% were current/recent people who inject drugs (PWID); 8% reported ongoing use of medication-assisted treatment (MAT) for opioid use disorder; 9% had a body mass index of at least 30 kg per m²; and median baseline HCV RNA level was 5.4 log₁₀ IU/mL.

The primary endpoint was the percentage of participants with sustained virologic response 12 weeks post-treatment (SVR12) in the intention-to-treat (ITT) population. The overall SVR12 rate was 96.2% (275/286); no participants experienced virologic failure. Two subjects who did not achieve SVR12 were reinfected with HCV based on differences in HCV genotypes or subtype clades between the baseline and follow-up periods.

The overall safety profile of Maviret in participants with acute HCV infection in study M20-350 was consistent with that observed in subjects with chronic HCV infection. There were no serious adverse reactions and/or adverse reactions leading to treatment discontinuation among subjects with acute HCV infection.

Although the design of Study M20-350 included adolescents, none were enrolled. However, the use of Maviret in pediatric patients with acute HCV infection is supported by extrapolation of the totality of evidence, including safety and efficacy from adult patients with acute HCV infection and from both adult and pediatric patients with chronic HCV infection.

Overall, the benefit-harm-uncertainty profile was favorable for Maviret for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about Maviret, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.