Regulatory Decision Summary for Descovy

The proposed new indication for Descovy in HIV-1 PrEP in at-risk adult men who have sex with men (MSM) and transgender women (TGW) who have sex with men was supported by the safety and efficacy results from a randomized, double-blind, active-controlled, multicentre Phase 3 study DISCOVER (GS-US-412-2055). This study compared once daily Descovy to Truvada in 5262 HIV-seronegative men and 73 transgender women. At baseline, 905 participants (17%) reported receiving Truvada for PrEP, of which 465 were randomized to Descovy. No individuals who were at-risk of HIV-1 acquisition from receptive vaginal sex were recruited in the DISCOVER study and therefore this population is excluded from the authorized PrEP indication. Study participants maintained a high risk of sexual HIV-1 acquisition as indicated by high rates of rectal gonorrhea (Descovy, 22/100 person-years; Truvada, 21/100 person-years), rectal chlamydia (28/100 person-years in both treatment groups), and syphilis (10/100 person-years in both treatment groups) during the study.

The primary outcome in the DISCOVER study was the incidence of documented HIV-1 infection per 100 person-years in participants randomized to Descovy and Truvada (with a minimum follow-up of 48 weeks and at least 50% of participants having 96 weeks of follow-up). After a median follow-up period of 86 and 87 weeks, respectively, HIV-1 infections were observed in 7 subjects in the Descovy group and 15 subjects in the Truvada group, which corresponds to HIV-1 incidence rate of 0.160 and 0.342 infections per 100 person-years, respectively. Descovy was non-inferior to Truvada with respect to the primary efficacy endpoint with the rate ratio of HIV-1 infections per 100 person-years of 0.468 (95% CI: 0.19, 1.15; the pre-specified non-inferiority margin was 1.62). The efficacy results were similar across the subgroups of age, race, baseline Truvada for PrEP use, and gender identity.

No direct safety and efficacy data for Descovy in HIV-1 PrEP in at-risk adolescents weighing at least 35 kg was provided in this SNDS. However, the HIV-1 PrEP indication in this population, excluding individuals at risk from receptive vaginal sex, was supported by extrapolation of data from the DISCOVER study in adults together with additional data from safety and pharmacokinetic studies in previously conducted trials. This extrapolation was possible due to known similar Descovy pharmacokinetic exposures between adults and adolescents and same sexual risk of HIV-1 acquisition.

Descovy was generally well tolerated in the DISCOVER study. The most common adverse events were diarrhea, headache, nausea, and abdominal pain. The proportion of participants who discontinued treatment with Descovy due to adverse events was 1.3%. There were no study drug-related deaths.

The main risk associated with the use of Descovy for HIV-1 PrEP is related to development of drug resistance. Therefore, Descovy used for PrEP must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initiating and at least every 3 months during use, and upon diagnosis of any other sexually transmitted infections. In addition, when prescribing Descovy for HIV-1 PrEP, healthcare providers must counsel all uninfected individuals to strictly adhere to the recommended Descovy dosing schedule because the effectiveness of Descovy in reducing the risk of acquiring HIV-1 was strongly correlated with adherence.

Taken together, the overall benefit-harm-uncertainty profile of Descovy in HIV-1 PrEP in at-risk uninfected adults and adolescents weighing at least 35 kg (excluding individuals at-risk from receptive vaginal sex) is considered to be positive.

In this SNDS, the Descovy Product Monograph was updated with Week 48 safety and efficacy data from a single arm, open-label study GS-US-292-1825 in 55 HIV-1 infected, virologically-suppressed patients with ESRD (estimated CrCl < 15 mL/minute) on chronic hemodialysis. At Week 48, 81.8% (45/55) patients maintained virologic suppression (HIV-1 RNA < 50 copies/mL). Although pharmacokinetic exposures of emtricitabine and tenofovir were higher in patients with ESRD requiring chronic hemodialysis compared to patients with normal renal function, the safety profile was comparable between these groups of patients. Based on the results of study GS-US-292-1825, the Descovy Product Monograph states that no dose adjustment of Descovy is required in adult individuals with ESRD (estimated CrCl < 15 mL/minute) on chronic hemodialysis.

Based on the data submitted in this SNDS, the overall benefit-harm-uncertainty profile of Descovy is considered to remain favorable under the conditions of use described in the Descovy Product Monograph at this time.