Regulatory Decision Summary for Delstrigo
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?
This New Drug Submission (NDS) was filed to obtain market authorization for Delstrigo, a fixed-dose combination of doravirine/lamivudine/tenofovir disoproxil fumarate, as a complete regimen for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adult patients without past or present resistance to doravirine, lamivudine or tenofovir.
Why was the decision issued?
Health Canada considers that the overall benefit-risk profile of Delstrigo is favorable when used as a complete regimen for the treatment of adult patients with HIV-1 infection without past or present evidence of viral resistance to doravirine, lamivudine, or tenofovir.
Delstrigo is a fixed dose combination of doravirine, lamivudine and tenofovir disoproxil fumarate. The recommended treatment regimen of Delstrigo is a single tablet once daily without regard to food.
The indication for Delstrigo is supported primarily by safety and efficacy data from an active-controlled, double-blind Phase 3 study in ART treatment-naïve HIV-1-infected adult patients (Drive-Ahead), which was designed to test for non-inferiority against the approved regimen consisting of efavirenz (NNRTI) in combination with 2 NRTIs (emtricitabine and tenofovir disoproxil fumarate).
The primary efficacy endpoint in the Drive-Ahead study was the proportion of patients with plasma HIV-1 RNA <50 copies/mL (virologic suppression) at Week 48 using the FDA Snapshot method. Delstrigo was demonstrated to be non-inferior to the active comparator with 84% vs. 81% of treated patients achieving virologic suppression at Week 48, resulting in a treatment difference (95% CI) of 3.5% (-2%, 9%). The immunologic response measured by an increase in CD4+ T-cells from baseline to Week 48 was also similar between Delstrigo and the active comparator. The efficacy results for Delstrigo were consistent across different demographic groups and baseline disease characteristics. Treatment failure rates were similar between Delstrigo and the active comparator, and corresponded to 11% vs. 10%, respectively. Few patients receiving Delstrigo had evidence of treatment-emergent genotypic or phenotypic resistance to doravirine, lamivudine and/or tenofovir disoproxil fumarate.
Delstrigo was generally well tolerated. The most common adverse events that occurred in patients treated with Delstrigo were dizziness, nausea, abnormal dreams, fatigue, headache, insomnia and diarrhea. Discontinuations due to adverse events were similar between Delstrigo and the active comparator. There were no treatment-related deaths.
Delstrigo is expected to have few drug-drug interactions. For clinically meaningful interactions, appropriate recommendations for contraindication, avoidance of co-administration, or dose adjustment have been included in the Product Monograph for Delstrigo.
The main risks associated with the use of Delstrigo are relevant to lamivudine and/or tenofovir disoproxil fumarate and include: acute exacerbations of HBV in HIV-1/HBV co-infected patients after discontinuation of Delstrigo; bone loss and mineralization defects; nephrotoxicity; and lactic acidosis and severe hepatomegaly with steatosis. These risks are presented in the Product Monograph for Delstrigo along with appropriate mitigating measures.
The uncertainties concerning Delstrigo are typical of any new antiretroviral regimen and include: relatively small number of HIV-1-infected patients exposed to the drug to date; the lack of long term safety and efficacy data; potential for development of resistance; and use in pregnancy.
The risks and uncertainties associated with the use of Delstrigo are manageable through the inclusion of appropriate contraindications, warnings and cautionary statements in the Product Monograph for Delstrigo and through the risk management plan to be effected by the sponsor.
Based on the data submitted, Health Canada considers that the anticipated benefits of Delstrigo outweigh the potential risks under the conditions of use described in the Product Monograph for Delstrigo at this time.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.