Regulatory Decision Summary for Maviret

The indication of Maviret in the treatment of chronic hepatitis C virus (HCV) infection in pediatric patients 3 years to less than 12 years of age and weighing ≥ 12 kg is supported by the efficacy, pharmacokinetic and safety data from Part 2 of the open-label, multicenter Phase 2/3 DORA trial. The recommended Maviret formulation for these patients is granules in sachets containing glecaprevir 50 mg/pibrentasvir 20 mg per sachet. The dosage of Maviret granules is based on body weight.

Part 2 of the DORA trial was conducted in 80 pediatric patients 3 years to less than 12 years of age with HCV genotype 1-4 infection without compensated cirrhosis and who were either treatment-naïve or treatment-experienced to interferon (IFN) with or without ribavirin (RBV). Patients received weight based Maviret granules in sachets for 8, 12 or 16 weeks. Eighteen patients received the initial lower dose of glecaprevir 40 mg/pibrentasvir 15 mg and 62 patients received the final recommended dose of glecaprevir 50 mg/pibrentasvir 20 mg. The median age was 7 years (range: 3 to 11). The sustained virologic response 12 weeks after the end of treatment (SVR12) for patients who received the final recommended dose of Maviret granules was 98.4% (61/62). No patients taking the final recommended dose of Maviret experienced virologic failure.

The pharmacokinetics of glecaprevir and pibrentasvir in HCV-infected pediatric patients 3 years to less than 12 years of age was generally within the safe and efficacious range observed in adult patients.

The safety profile of Maviret in Part 2 of the DORA trial was favourable. The adverse reactions were consistent with those observed in clinical trials of Maviret in adults with the exception of vomiting (occurring at approximately 8%), rash, and abdominal pain upper (each occurring at approximately 4%) which were observed more frequently compared to adults. Other adverse reactions observed in greater than or equal to 3% of patients include fatigue and headache, each occurring at approximately 8%, and diarrhoea and nausea, each occurring at approximately 4%. One patient discontinued treatment due to a Grade 3 adverse reaction of erythematous rash. All other adverse reactions were Grade 1 or 2 and no patients interrupted treatment due to an adverse reaction.

There is uncertainty about the safety and efficacy of Maviret in pediatrics infected with HCV genotype 5 or 6, those with compensated cirrhosis and those previously treated with a regimen containing sofosbuvir as these patients were not included in Part 2 of the DORA trial. This information is presented in the Maviret Product Monograph.

Based on the review of above data, it is considered that the benefit-harm-uncertainty of Maviret in the treatment of HCV infection in pediatric patients 3 years to less than 12 years of age and weighing ≥ 12 kg is favourable when used as directed in the Maviret Product Monograph at this time.