Regulatory Decision Summary for Biktarvy

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.


Product type:

Drug

Medicinal ingredient(s):

emtricitabine, bictegravir sodium, tenofovir alafenamide hemifumarate

Therapeutic area:

Antivirals For Systemic Use

Type of submission:

Supplement to a New Drug Submission

Control number:

226658
What was the purpose of this submission?

 

The purpose of this Supplemental New Drug Submission (SNDS) was to extend the indication for Biktarvy to human immunodeficiency virus 1 (HIV-1)-infected pediatric patients weighing ≥ 25 kg with no known substitution associated with resistance to the individual components of Biktarvy. In addition, the Biktarvy Product Monograph was updated with the long-term safety and efficacy data from Phase 3 clinical trials in HIV-1-infected treatment-naïve adult patients.

 

Why was the decision issued?

 

To support the proposed indication for Biktarvy in HIV-1-infected pediatric patients weighing ≥ 25 kg, the sponsor submitted the safety, efficacy and pharmacokinetic results from study GS-US-380-1474. This is a Phase 2/3b open-label clinical trial in 100 HIV-1-infected, virologically suppressed pediatric patients divided into 2 cohorts, i.e. adolescents between the ages of 12 to less than 18 years weighing ≥ 35 kg (N = 50; Cohort 1) and children between the ages of 6 to less than 12 years weighing ≥ 25 kg (N = 50; Cohort 2). After switching to Biktarvy from their current antiretroviral regimens, 98% (49/50) and 100% (50/50) of patients in Cohort 1 and Cohort 2, respectively, remained virologically suppressed (HIV-1 RNA < 50 copies/mL) at Week 48 and Week 24, respectively; the mean change from baseline in CD4 + cell count was - 22 cells/mm3 and - 24 cells/mm3, respectively. There was no evidence of treatment-emergent resistance to Biktarvy in any Cohort.

The safety profile of Biktarvy in HIV-1-infected pediatric patients weighing ≥ 25 kg in study GS-US-380-1474 was generally similar to previously established safety profile in HIV-1-infected adult patients. Adverse reactions were reported in 10% of pediatric patients. The most commonly reported adverse reactions were upper respiratory tract infection, diarrhea, and cough. There were no Grade 3 or Grade 4 adverse reactions. One patient had Grade 2 adverse reactions of insomnia and anxiety that led to discontinuation of Biktarvy.

The pharmacokinetic analysis of study GS-US-380-1474 showed that the exposures of bictegravir, emtricitabine, tenofovir alafenamide, and tenofovir (the main metabolite of tenofovir alafenamide) in HIV-1-infected pediatric patients weighing ≥ 25 kg were within the exposure range observed previously in HIV-1-infected adult patients.

Taken together, the data from study GS-US-380-1474 support the safety and efficacy of Biktarvy in HIV-1-infected pediatric patients weighing ≥ 25 kg who have no known resistance-associated mutations to the individual components of Biktarvy.

To support the long-term safety and efficacy of Biktarvy in HIV-1-infected treatment-naïve adult patients, the sponsor submitted Week 96 data from two ongoing Phase 3 trials, GS-US-1489 and GS-US-1490. Week 48 data from these trials supported the initial approval of Biktarvy in Canada. The non-inferiority of Biktarvy compared to the control antiretroviral regimens established at Week 48 was maintained through Week 96. In Study GS-US-1489, 88% of patients who received Biktarvy versus 90% of patients who received the control regimen remained virologically suppressed (HIV RNA < 50 copies/mL) at Week 96. In Study GS-US-1490, 84% of patients who received Biktarvy versus 87% of patients who received the control regimen remained virologically supressed at Week 96. In both trials, the overall incidence and types of common adverse reactions were generally similar between Biktarvy and the control antiretroviral regimes at Week 96.

Based on the data submitted, Health Canada considers that the overall benefit-harm-uncertainty profile of Biktarvy remains positive when used under conditions described in the Biktarvy Product Monograph at this time.

 

Decision issued

Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.