Regulatory Decision Summary for Vocabria and Cabenuva

The purpose of this Supplemental New Drug Submission (SNDS) was to update the Vocabria and Cabenuva Product Monograph with the long-term efficacy and safety data from the pivotal Phase 3 FLAIR study. Based on these data, it was proposed that the oral lead-in phase with Vocabria be optional. Upon review, an option to initiate injection therapy with Cabenuva without the oral lead-in phase with Vocabria is provided in the Dosage and Administration section of the Product Monograph.

The original approval of Vocabria and Cabenuva was supported by Week 48 safety and efficacy data from Phase 3 randomized, multicenter, active-controlled, parallel-arm, open-label, non-inferiority FLAIR (201584) and ATLAS (201585) trials. In this SNDS, the Vocabria and Cabenuva Product Monograph was updated with Week 96 and Week 124 data from the FLAIR trial.

In the FLAIR trial, HIV-1-infected, antiretroviral treatment-naive patients (n = 629) received a standard of care antiretroviral regimen (CAR) for 20 weeks. Patients who were virologically suppressed (HIV-1 RNA <50 copies/mL, n = 566) were then randomized to receive the Vocabria and Cabenuva regimen (oral lead-in + injections) or to remain on CAR. The primary efficacy endpoint was the proportion of patients with plasma HIV-1 RNA ≥50 copies/mL at Week 48. It was demonstrated that Cabenuva was non-inferior to the CAR with 2% of patients having plasma HIV-1 RNA ≥50 copies/mL at Week 48 in both study arms. At Week 96, the efficacy results remained consistent with the results at Week 48 with 3.2% of patients having plasma HIV-1 RNA ≥50 copies/mL in both study arms.

The FLAIR trial also included an extension phase where the safety and efficacy of Cabenuva was evaluated in patients who switched (at Week 100) from their CAR to Cabenuva, with and without an oral lead-in phase, creating an oral lead-in (OLI) group (n = 121) and a direct to injection (DTI) group (n = 111). At Week 124, the proportion of subjects with HIV-1 RNA ≥50 copies/mL was 0.8% and 0.9% for the OLI and DTI arms, respectively. The rates of virologic suppression (HIV-1 RNA <50 copies/mL) were similar in both the OLI group (113/121 [93.4%]) and the DTI group (110/111 [99.1%]). Initiating the Cabenuva regimen with DTI did not identify any new safety concerns related to omitting the OLI phase. Based on these data, the Product Monograph was updated to allow for initiation of Cabenuva without the oral lead-in phase with Vocabria.

At Week 96 and Week 124, the overall safety profile in the FLAIR trial was consistent with that observed at Week 48, with no new safety findings identified.

Based on the review of submitted data, the benefit-harm-uncertainty of Vocabria and Cabenuva remains favorable under conditions of use described in the Vocabria and Cabenuva Product Monograph at this time.

For further details about Vocabria and Cabenuva, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.