FDA approves twice-yearly injectable lenacapavir for PrEP
By Jessica Bloome, MD, MPH
On June 18, the FDA approved the latest medication for HIV prevention – long-acting injectable lenacapavir (LEN), a subcutaneous injection administered every 6 months. Lenacapavir will be marketed in the United States with the brand name Yeztugo®.
Lenacapavir acts as a capsid inhibitor, preventing HIV capsid assembly, nuclear transport, and other steps in viral replication. In 2024, Science named it “Breakthrough of the Year” for the basic science discoveries that led to its unique mechanism of action, as well as impressive clinical trial outcomes
FDA-approval was based upon the PURPOSE 1 and PURPOSE 2 clinical trials. Both studies were randomized, double-blind active-controlled studies of lenacapavir and daily oral TDF/FTC (Truvada®) for PrEP starting in 2021. The primary outcomes compared HIV incidence in the lenacapavir group with the background HIV incidence in the screened populations.
PURPOSE 1 enrolled over 5,300 cisgender women ages 16-25 in South Africa and Uganda. This study also included an arm evaluating oral TAF/FTC (Descovy®) for PrEP in cisgender women. In June 2024, interim reporting of zero infections in the lenacapavir arm led to early discontinuation of the blinded phase of the study due to efficacy, as recommended by the independent monitoring board. The study demonstrated superiority of lenacapavir to both background HIV incidence and oral TDF/FTC for PrEP. The TAF/FTC group did not have a significant difference in HIV infections compared to the TDF/FTC group.
PURPOSE 2 enrolled over 3,200 cisgender men and gender-diverse individuals in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the U.S. There were two HIV infections in the lenacapavir group, demonstrating a 96% reduction in HIV incidence compared to background incidence, and 89% reduction compared to oral TDF/FTC.
Both trials are notable for efforts to promote inclusion of groups highly impacted by the HIV epidemic. PURPOSE 1 included adolescents as well as pregnant and lactating women, an important landmark for a phase 3 HIV prevention trial, with no signal of safety concerns to date. In the PURPOSE 2 study, 67% of participants identified as non-White, and 22% as gender diverse. This is also the first phase 3 HIV prevention trial to enroll transgender men and non-binary individuals.
The full FDA prescribing label can be found here. For more on the lenacapavir clinical trials and injectable PrEP implementation strategies, check out getSFcba’s recent webinar, The Future of Injectable PrEP, featuring Dr. Albert Liu, Clinical Research Director of Bridge HIV, San Francisco Department of Public Health, and our colleagues from Whitman-Walker Health in Washington, D.C.
