Regulatory Decision Summary for EDURANT

Health Canada considers that the benefit/risk profile of Edurant is favorable, when used in combination with other antiretroviral agents, for the treatment of HIV-1 infection in antiretroviral treatment-naïve patients 12 years of age and older and weighing at least 35 Kg with HIV-1 ribonucleic acid (RNA) levels less than or equal to 100,000 copies/mL.

The use of Edurant in treatment-naïve patients over 12 years of age was supported based on an ongoing Phase II, open-label, single arm study. The study was carried out to assess the pharmacokinetics, safety, tolerability and efficacy of Edurant over 48 weeks of therapy. Edurant was administered at 25 mg once daily in combination with an investigator-selected background regimen containing two nucleoside reverse transcriptase inhibitors, either abacavir or zidovudine or tenofovir disoproxyl fumarate in combination with lamivudine or emtricitabine.

The primary efficacy endpoint of HIV-1 RNA levels of < 50 copies/mL was measured at week 24. In addition, efficacy, safety and tolerability, and pharmacokinetics of Edurant were evaluated over a 48-week treatment period.

Results from this study indicated that:

• Edurant pharmacokinetics at a 25 mg once daily dose in HIV-1 infected adolescents aged 12 to < 18 years appeared to be similar to those in HIV-1 infected adults.
• Efficacy in terms of viral suppression of HIV-1 RNA to < 50 copies/mL at week 48 was achieved in 72% (26/36) overall and 78.6% (22/28) for subjects with a viral load ≤ 100,000 copies/mL. The virologic failure rate was 25% (9/36) at week 48 and 36% (13/36) after week 48. The mean increase in CD4+ T-cell count from baseline was 201 cells/μL) overall and 214.5 cells/μL at week 48 (Non-Completer = Failure) in subjects with baseline viral load ≤ 100,000 copies/mL.
• The safety profile of Edurant in the 36 adolescents aged 12 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 Edurant in a small group of adolescents, thus efficacy and safety results are limited. The efficacy of Edurant in pediatric patients aged 12 to < 18 years appeared to be lower than that for adults (90.2% response rate was reported for Edurant in adults as compared to 78.6% in adolescents). However, 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.

With regards to resistance-associated mutations (RAMs), of the 9 patients who had virologic failure by week 48, 5 developed treatment-emergent Edurant RAMs. One additional patient developed non-nucleoside reverse transcriptase inhibitor RAMs other than Edurant RAMs. For 4 out of the 6 subjects who developed non-nucleoside reverse transcriptase inhibitor RAMs, at least 1 treatment-emergent nucleoside reverse transcriptase inhibitor RAM was detected at the same time point. Non-nucleoside reverse transcriptase inhibitor RAMs were not detected in the four subjects with virologic failure after the week 48 cut-off. The observed treatment-emergent RAMs were previously identified in adults.

Based on the evidence provided the anticipated benefits of Edurant as another treatment option for patients aged 12 to < 18 years are considered to outweigh the potential risks under the conditions of use recommended in the Endurant Product Monograph at this time.