Therapy Areas: AIDS & HIV
Gilead Presents New Findings on Profile of Descovy for Potential Use as HIV Pre-exposure Prophylaxis Compared with Truvada
25 July 2019 - - US-based biopharmaceutical company Gilead Sciences, Inc. (NASDAQ: GILD) has presented additional results from the DISCOVER trial evaluating an investigational use of Descovy (emtricitabine 200 mg and tenofovir alafenamide 25 mg tablets; F/TAF) for HIV pre-exposure prophylaxis, the company said.
In a sub-analysis of the DISCOVER trial, Descovy reached intracellular drug concentration levels above the estimated protective threshold significantly more quickly than Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg tablets; F/TDF), and additional pharmacokinetic data confirm that these drug concentration levels persist longer than Truvada.
The results were presented at the 10th International AIDS Society Conference on HIV Science (IAS 2019) being held in Mexico City.
In April, Gilead submitted a supplemental New Drug Application to the US Food and Drug Administration for once-daily Descovy for PrEP. A Priority Review voucher was submitted with the filing, leading to an anticipated review time of six months.
Descovy was approved in the United States in 2016 for the treatment of HIV-1 infection in combination with other antiretroviral agents, and the use of Descovy for a PrEP indication is investigational.
Descovy and Truvada have a Boxed Warning in their US product label regarding the risk of post-treatment acute exacerbation of hepatitis B; Truvada for PrEP also includes a Boxed Warning regarding the risk of drug resistance with use of Truvada for PrEP in undiagnosed early HIV infection.
These results were based on a sub-analysis of the DISCOVER trial, a two-year Phase 3 randomised, controlled, double-blind study evaluating the safety and efficacy of the investigational use of once-daily Descovy for PrEP compared with Truvada for PrEP.
The study enrolled adult men and transgender women who have sex with men who were both at substantial and sustained risk for sexually acquired HIV infection.
DISCOVER trial sites included STI clinics, LGBTQ health centers, and other clinical practices that are located in areas with high background rates of HIV and that serve populations with among the highest risk of HIV infection.
The primary endpoint of the DISCOVER trial was the incidence of documented HIV infection per 100 person-years, with a minimum follow-up of 48 weeks and at least 50% of participants having 96 weeks of follow-up.
Descovy met the primary endpoint of non-inferiority.
The most common treatment-emergent adverse events (≥25%; all grades) were bacterial sexually transmitted infections, including anal chlamydia infection, oropharyngeal gonococcal infection and rectal gonorrhea.
Common study drug-related side effects (≥ 1 %; all grades) included diarrhea, nausea, headache and fatigue.
There were no differences in HIV risk factors, acquired STIs or adherence between the two study drug arms in DISCOVER.
Overall, study participants randomized to Descovy for PrEP had a significantly reduced time to achieve a 90% effective concentration of tenofovir diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs), as compared with participants taking Truvada.
At Week 4, levels of TFV-DP in PBMCs were 6.3-fold higher with Descovy compared with Truvada, resulting in 98% of participants receiving Descovy had drug levels above the EC90 compared with 68% of participants taking Truvada.
Pharmacokinetic data from separate PK studies demonstrate that after using drugs for 14-28 days, F/TAF users who stop drug still maintain TFV-DP concentrations above the EC90 for at least 60% longer than F/TDF users.
Additionally, at IAS, Gilead presented data assessing renal adverse events in people at risk for HIV acquisition taking Truvada for PrEP. These results of an analysis of multi-national Truvada for PrEP utilisation data in MSM are summarised in Poster #TUPEC393.
The use of Descovy for the prevention of HIV is investigational and has not been determined to be safe or efficacious and is not approved anywhere globally.