Regulatory Decision Summary for Biktarvy
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.
Type of submission:
What was the purpose of this submission?
The purpose of the New Drug Submission was to seek market authorization for Biktarvy, a fixed dose combination of bictegravir/emtricitabine/tenofovir alafenamide, as a new regimen for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adult patients with no known substitution associated with resistance to the individual components of the combination.
Why was the decision issued?
Health Canada considers that the overall benefit-risk profile of Biktarvy is favorable for the treatment of adult patients with HIV-1 infection with no known mutation associated with resistance to the individual components of the combination is identified prior to clinical use.
Biktarvy is a fixed dose combination of bictegravir/emtricitabine/tenofovir alafenamide. The recommended treatment regimen of Biktarvy is a single tablet once daily without regard to food in HIV-1 infected adult patients.
The primary efficacy and safety data in support of Biktarvy was based on interim 48-week data of four active controlled, double blind Phase 3 studies. Two clinical studies were in treatment-naïve HIV-1 infected adult patients and other two studies were in virologically suppressed HIV-1 infected adult patients. The primary efficacy endpoint in studies with treatment-naïve HIV-1 infected adult patients was the proportion of subjects with plasma HIV-1 RNA <50 copies per millilitre (c/mL) at Week 48 using the Snapshot algorithm for the Intent-to-Treat exposed population as compared to active control. The primary efficacy endpoint in studies with virologically suppressed HIV-1 infected adult patients was the evaluation of the proportion of patients with HIV-1 RNA ≥50 copies/mL in treatment group at Week 48 (Snapshot algorithm) as compared to active control. Biktarvy was demonstrated to be non-inferior to active control groups in all studies. Treatment failure rates were low and no HIV-1 patients receiving Biktarvy had treatment emergent genotypic or phenotypic resistance to any of the components in the resistance analysis population in both treatment-naïve and virologically suppressed studies. Furthermore, Biktarvy is indicated for the treatment of human immunodeficiency virus-1 (HIV-1) infected adult patients with no known substitution associated with resistance to the individual components of the combination.
Biktarvy is a well-tolerated regimen without significant toxicities or drug-drug interactions and may thus simplify on-treatment monitoring. The most common side effects are diarrhea, headache, nausea, fatigue, dizziness and abnormal dreams. Death is rare and none of the death incidents in the clinical trials were associated with study drugs. Biktarvy has favorable bone and renal safety profiles during 48 weeks study period although long-term bone and renal safety are not known. Due to lack of adequate safety data use of Biktarvy in severe hepatic impaired patients Biktarvy is not recommended. It is also not recommended in patients with severe renal impairment (creatinine clearance [CrCl] <30 mL/Min).
Potential risks associated with Biktarvy include: resistant HIV-1 strains to the individual components of the combination; Hepatitis B Virus (HBV) reactivation/acute exacerbation of HBV in patients with HBV co-infection after discontinuation of Biktarvy; use in severe hepatic impairment and/or severe renal impaired patients; pregnant women or breast-feeding women. Potential drug-drug interactions with use of Biktarvy have been identified in a number of interactions which are likely to be of clinical significance. Appropriate recommendations for dose adjustments of the co-administered drug, avoidance of co-administration, or contraindications have been included in the prescribing information of Biktarvy.
Based on the data submitted, Health Canada considers that the anticipated benefits of Biktarvy outweigh the potential risks under the conditions of use described in the Product Monograph for Biktarvy at this time.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.