Regulatory Decision Summary for Vocabria and Cabenuva

The purpose of this Supplemental New Drug Submission (SNDS) was to expand the indication for Vocabria and Cabenuva to human immunodeficiency virus type 1 (HIV-1)-infected and virologically suppressed adolescent patients at least 12 years of age and weighing at least 35 kg. In addition, the Vocabria and Cabenuva Product Monograph was updated with the long-term efficacy and safety data from the Phase 3b ATLAS-2M study.

The proposed expansion of the indication for Vocabria and Cabenuva to adolescent patients at least 12 years of age and weighing at least 35 kg was based primarily on the safety, tolerability and pharmacokinetic data from an ongoing Phase 1/2 multicenter, open-label, non-comparative study, MOCHA (IMPAACT 2017). In this study, 23 HIV-1–infected and virologically suppressed adolescents were assigned to 1 of 2 groups of Cohort 1, 1C or 1R, based on their background antiretroviral regimen. In group 1C, patients (n = 8) received one 30 mg cabotegravir tablet daily for 1 month, followed by three monthly cabotegravir injections (Month 1: 600 mg injection, Months 2 and 3: 400 mg injection), while continuing background antiretroviral therapy. In group 1R, patients received one 25 mg rilpivirine tablet (n = 15) daily for 1 month, followed by three monthly rilpivirine injections (n = 13) (Month 1: 900 mg injection, Months 2 and 3: 600 mg injection), while continuing background antiretroviral therapy. At baseline, in group 1C, the median age of patients was 14.5 years; the median weight was 57.2 kg (range: 43.0, 73.5); 25% were female; 100% were non-White; and no participant had a CD4+ cell count <350 cells per mm³ (median: 725; range: 629 to 924). In group 1R, the median age of patients was 17 years; the median weight was 63.0 kg (range: 44.1, 98.5); 53% were female; 73% were non-White; and no participant had a CD4+ cell count <350 cells per mm³ (median: 827; range: 439 to 1,509). The data from an interim analysis at Week 16 was available for review. This data did not identify any new safety concerns in adolescents when compared with the safety profile of cabotegravir plus rilpivirine in adults. The observed pharmacokinetic parameters in adolescents met the exposure targets based on adult exposure data for both oral and injectable cabotegravir and injectable rilpivirine. This was further supported by the population PK (PopPK) analyses using the data from the MOCHA trial and relevant clinical studies in adults. The MOCHA study is ongoing and therefore, long-term data will be available in the future.

In this SNDS, the Vocabria and Cabenuva Product Monograph was also updated with Week 96 safety and efficacy data from a Phase 3b randomised, multicenter, parallel-arm, open-label, non-inferiority ATLAS-2M study in 1045 HIV-1-infected virologically supressed adult patients. The Week 48 data from this trial was reviewed by Health Canada in a previous submission and supported the every 2 month dosing regimen of Cabenuva. Specifically, at Week 48, the every 2 month dosing regimen of Cabenuva was non-inferior to every month dosing regimen with 1.7% and 1.0% of patients having plasma HIV-1 RNA greater or equal to 50 copies/mL (i.e. the primary efficacy endpoint), respectively (adjusted treatment difference of 0.8%; 95% CI: -0.6, 2.2). The efficacy results at Week 96 were consistent with the results of the Week 48 primary endpoint analysis with 2.1% and 1.1% of patients having plasma HIV-1 RNA ≥50 c/mL in the every 2 month dosing regimen group and every month dosing regimen group, respectively (adjusted treatment difference of 1.0; 95% CI: -0.6, 2.5). Through Week 96, the total number of confirmed virologic failures in the study was 1.7% in the every 2 month dosing regimen group and 0.4% in the every month dosing regimen group. The overall safety profile at week 96 was consistent with that observed at Week 48 and there was no new safety issues identified. The pharmacokinetic analysis demonstrated that the pre-dose exposure to injectable cabotegravir and rilpivirine in the every 2 month dosing regimen group was above the minimum effective plasma concentration.

Based on the review of submitted data, it is considered the benefit-harm-uncertainty of Vocabria and Cabenuva is favorable in the treatment of HIV-1-infected and virologically suppressed adolescent patients 12 years of age and older and weighing at least 35 kg under the conditions of use described in the Vocabria and Cabenuva Product Monograph at this time. The Week 96 efficacy, safety and pharmacokinetic data from the ATLAS-2M study continues to support the every 2 month dosing regimen of Cabenuva.

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