Regulatory Decision Summary for Genvoya

Health Canada considers that the overall benefit-risk profile of Genvoya, a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection, is favourable when used for the treatment of HIV-1 infected adult patients with ESRD on chronic hemodialysis.

Genvoya is a fixed-dose combination (FDC) tablet containing elvitegravir (EVG), cobicistat (COBI), emtricitabine (FTC) and tenofovir alafenamide hemifumarate (TAF). The recommended dose is one tablet per day for adults and children weighing ≥ 25 kg.

The use of Genvoya in patients with ESRD is supported by Week 48 results from a Phase 3b open-label study in 55 HIV-1-infected adult patients with estimated creatinine clearance (eCrCl) < 15 mL/minute on chronic hemodialysis who were virologically suppressed. The primary endpoint in this study was safety and tolerability at Week 48. The secondary endpoints included efficacy and pharmacokinetics of Genvoya components also at Week 48.

Genvoya was generally well tolerated in HIV-1-infected adult patients on chronic hemodialysis. Adverse drug reactions were reported in 11% of patients. There were no Grade 3 or higher treatment emergent adverse events that were considered to be drug-related. The majority of patients had at least 1 adverse event (AE). The most common AEs were nausea, hyperkalemia, and pneumonia. Overall, the AE profile was consistent with that expected in this study population. Only one discontinuation due to AEs was considered related to study drug (allergic pruritus) and there were no study drug-related serious adverse events (SAEs) through Week 48. There was one death due to heart failure, which was not considered to be related to Genvoya. There were no clinically relevant changes from baseline in median values for hematology, clinical chemistry, or liver abnormalities through Week 48, and no clinically relevant changes for serum metabolic parameters.

The efficacy results showed that the virologic suppression was maintained during the study with 81.8% (45/55) of patients with HIV-1 RNA < 50 copies/mL at Week 48. Two patients had HIV-1 RNA ≥ 50 copies/mL by Week 48. Seven patients discontinued the study drug due to AE or other reasons while suppressed. One patient did not have an HIV-1 RNA measurement at Week 48. The CD4 cell count remained stable through Week 48.

Pharmacokinetic analysis showed that the exposures of EVG, COBI and TAF were consistent with the range of historical data following the administration of Genvoya to HIV-1 infected patients without renal impairment. Exposures of TFV (the major metabolite of TAF) and FTC were significantly higher compared to historical data obtained following the administration of Genvoya to HIV-1 infected patients with normal renal function, or with mild to moderate renal impairment.

Based on the above data, Genvoya can be used in HIV-1-infected adult patients with ESRD (eCrCl < 15 mL/minute) on chronic hemodialysis and no dose adjustment is needed in these patients. However, Genvoya is not recommended in patients with eCrCL ≥ 15 and < 30 mL/minute, or < 15 mL/minute who are not on chronic hemodialysis, as the safety of Genvoya has not been established in these patients. No data are available to make dose recommendations in pediatric patients with renal impairment at this time.