Regulatory Decision Summary for Tivicay

Health Canada considers that the benefit/risk profile of Tivicay is favorable, when used in combination with other antiretroviral agents, for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-naïve and treatment-experienced integrase strand transfer inhibitor (INSTI)-naïve pediatric patients weighing at least 30 Kg.

The use of Tivicay in integrase INSTI-naïve patients weighing at least 30 kg to <40 kg is supported by an on-going Phase I/II, open-label, non-comparative study. The study was carried out to assess the pharmacokinetics, safety, tolerability and efficacy of Tivicay when administered prior to starting, and in combination with an optimized background regimen (OBT).

The primary objectives were to select a dolutegravir (Tivicay) dose for chronic dosing in children and adolescents that achieves similar exposures to those in ARV-naïve adult dose (50 mg once daily), and to evaluate safety and tolerability, and pharmacokinetics of Tivicay over 24-week and 48-week treatment periods.
Results from this study indicated that:

• Tivicay pharmacokinetics at a 35 mg once daily dose in HIV-1 infected children weighing 30 to <40 kg appeared to be comparable to those in HIV-1 infected ARV-naïve adults.
• Efficacy in terms of viral suppression of HIV-1 RNA to <50 copies/mL was achieved in 61% (14/23 (95% CI: 39%, 80%)) each for both Cohort I at Week 48 and Cohort IIA at Week 24. The median (minimum, maximum) increase in CD4+ T-cell count from baseline was 84 (-304, 380) cells/mm3 for Cohort I at Week 48; and 209 (-462, 725) cells/mm3 for Cohort IIA at Week 24.
• The safety profile of Tivicay in the 46 children and adolescents aged 6 to <18 years appeared to be similar to that in adults based on the very limited safety data. No new adverse drug reactions (ADRs) were reported other than those previously observed in adults.

The study was primarily carried out to assess the pharmacokinetics of Tivicay in a small group of children, thus efficacy and safety results are limited. Based on a similar course of the disease (HIV-1 infection) between the adult and pediatric populations, and comparable pharmacokinetic exposures, the extrapolation of adult efficacy data to the pediatric population as a method to support effectiveness in children was considered acceptable.

Based on the evidence provided, the anticipated benefits of Tivicay as a treatment option for patients weighing at least 30 kg to <40 kg are considered to outweigh the potential risks under the conditions of use recommended in the Product Monograph at this time.