Gilead's Descovy Demonstrates Non-Inferior Efficacy to Truvada for HIV PrEP with Superior Bone and Renal Safety Profile
Mar 15, 2019 08:35
CST Updated
08:35
Gilead Sciences
Antiviral Drug Developer
March 15, 2019 News /BioValleyBIOON/ -- U.S. pharmaceutical giant Gilead Sciences recently announced the results of the Phase III DISCOVER clinical trial evaluating Descovy (Chinese brand name: Dakewei; F/TAF; emtricitabine/tenofovir alafenamide, 200/25 mg) for HIV pre-exposure prophylaxis (PrEP). The study was conducted in men who have sex with men and transgender women at risk of sexually acquired HIV infection, assessing the efficacy and safety of once-daily Descovy (F/TAF, 200 mg/25 mg) for PrEP in comparison with Truvada (Chinese brand name: Shufatai; F/TDF; emtricitabine/tenofovir disoproxil fumarate, 200 mg/300 mg). The results demonstrated that once-daily Descovy was non-inferior to once-daily Truvada in preventing HIV infection, meeting both the primary and secondary endpoints of the study, and will support the submission of a supplemental application for the use of Descovy for PrEP. These data were recently presented at the 2019 Conference on Retroviruses and Opportunistic Infections (CROI) held in Seattle, United States.Meetingpublished above.
In this study, 5,387 participants, comprising men who have sex with men and transgender women, were randomized in a 1:1 ratio to receive either Descovy or Truvada. At baseline, all participants were confirmed to be at risk of HIV infection based on documented high-risk sexual behaviors. Among the 2,694 participants (4,370 patient-years) at risk of HIV-1 infection who received once-daily Descovy, 7 cases of HIV infection were reported (HIV incidence rate of 0.16 per 100 patient-years). Among the 2,693 participants (4,386 patient-years) at risk of HIV-1 infection who received once-daily Truvada, 15 cases of HIV infection were reported (HIV incidence rate of 0.34 per 100 patient-years).
Through rigorous statistical comparison of rate ratios, Descovy met the prespecified noninferiority criterion relative to Truvada: the upper bound of the 95% confidence interval for the HIV-1 infection rate ratio was below the prespecified noninferiority margin of 1.62 per 100 patient-years. Furthermore, subjects treated with Descovy demonstrated statistically significant advantages over those treated with Truvada in bone and renal laboratory parameters, meeting the prespecified secondary endpoints. At Week 48, the percent change in spine bone mineral density was +0.5% versus −1.1% (p < 0.001), and the change in hip bone mineral density was +0.2% versus −1.0% (p < 0.001). For renal parameters at Week 48, the change in estimated glomerular filtration rate (eGFR) was +1.8 mL/min versus −2.3 mL/min (p < 0.001).
Among the 22 HIV infections, five were likely acquired before the study began, 15 occurred at low or undetectable intracellular drug levels, and two occurred when moderate or expected intracellular drug levels were detected. Descovy and Truvada were well tolerated, with low discontinuation rates due to adverse events (1.3% and 1.8%, respectively). The most common adverse events (>15% in both groups) were similar across groups and included anal chlamydia, oropharyngeal gonorrhea, and rectal gonorrhea.No cases of Fanconi syndrome occurred in the Descovy group, whereas one case occurred in the Truvada group, leading to premature discontinuation of the study drug.
John McHutchison, Chief Scientific Officer and Head of Research and Development at Gilead Sciences, stated, “As the largest HIV prevention study conducted to date, the results from the DISCOVER trial clearly demonstrate that Descovy for PrEP exhibits a clinical profile comparable to the high efficacy of Truvada, along with a more favorable bone and renal safety profile. We look forward to submitting regulatory filings to health authorities for the PrEP indication of Descovy, offering it as a potentially important new option to prevent HIV infection in individuals, which will help advance national and global HIV prevention goals.”
In the United States, Descovy is approved in combination with other antiretroviral agents for the treatment of HIV infection in patients weighing ≥35 kg, but it is not indicated for PrEP. Truvada is indicated in combination with safer sex practices for HIV PrEP to reduce the risk of sexually acquired HIV in high-risk adults and adolescents weighing ≥35 kg. Both Descovy and Truvada carry a Boxed Warning in their respective product labeling regarding the risk of severe acute exacerbation of hepatitis B following discontinuation of treatment; the Truvada labeling also includes a warning regarding untreatedDiagnosisBlack Box Warning on the Risk of PrEP Resistance in Early HIV Infection. (Bioon.com)