Twice-yearly lenacapavir for HIV prevention reduced HIV infections by 96% and demonstrated superiority to daily Truvada in second pivotal phase III trial

There were 2 incident cases among 2,180 participants, corresponding to 99.9% of participants not acquiring HIV infection in the lenacapavir group. Twice-yearly lenacapavir also demonstrated superiority to once-daily Truvada  (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; F/TDF).

The trial, PURPOSE 2 ( NCT04925752 ), includes cisgender men, transgender men, transgender women, and gender non-binary individuals in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States who have sex with partners assigned male at birth. At interim analysis, the independent Data Monitoring Committee (DMC) confirmed that the PURPOSE 2 trial met its key efficacy endpoints of superiority of twice-yearly lenacapavir to both HIV (primary endpoint) and once-daily oral Truvada (secondary endpoint) for pre-exposure prophylaxis (PrEP). Therefore, the DMC recommended that Gilead stop the blinded phase of the trial and offer open-label lenacapavir to all participants.

“With such remarkable outcomes across two Phase III studies, lenacapavir has demonstrated the potential to transform the prevention of HIV and help to end the epidemic,” said Daniel O’Day, Chairman and Chief Executive Officer of Gilead. “Now that we have a comprehensive dataset across multiple study populations, Gilead will work urgently with regulatory, government, public health and community partners to ensure that, if approved, we can deliver twice-yearly lenacapavir for PrEP worldwide, for all those who want or need PrEP.”

This is the second pivotal Phase III trial to demonstrate superior efficacy for twice-yearly lenacapavir for the investigational use of HIV prevention as PrEP. In June 2024, the PURPOSE 1 trial, studying lenacapavir for PrEP among cisgender women in sub-Saharan Africa, was also unblinded early because it met its key efficacy endpoints.

The data from the PURPOSE 1 and PURPOSE 2 trials will support upcoming regulatory filings so that twice-yearly lenacapavir for PrEP, if approved, can be made available to multiple populations and communities around the world who are most in need of additional HIV prevention choices. Updates on regulatory filings for lenacapavir for PrEP will be shared as discussions with regulatory bodies progress. Gilead will begin a series of global regulatory filings by the end of 2024. This could support the initial launch of the first and only twice-yearly HIV prevention choice in 2025.

Gilead is executing an access strategy that prioritizes speed and enables the most efficient paths for the regulatory review and approval of lenacapavir for PrEP in regions around the world. This strategy will prioritize high-incidence, low-resource countries, which are primarily low- and lower-middle income countries. Gilead is committed to making lenacapavir available in the countries where the need is greatest, including expediting voluntary licensing partners to supply high-quality, low-cost versions of lenacapavir. Gilead is actively working to finalize these contracts.

Topline PURPOSE 2 Data

PURPOSE 2, a phase III, double-blind, multicenter, randomized study, is evaluating the safety and efficacy of twice-yearly subcutaneous lenacapavir for PrEP versus once-daily oral Truvada and background HIV incidence (bHIV) in more than 3,200 cisgender men, transgender men, transgender women and gender non-binary individuals aged 16 years or older who have sex with partners assigned male at birth. There were 88 trial sites in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States.

 Study participants were randomized in a 2:1 ratio to lenacapavir and Truvada, respectively. Because effective PrEP options already exist, there is broad consensus in the PrEP field that a placebo group would be unethical; thus, the trial used bHIV as the primary comparator and Truvada as a secondary comparator. There were 2 incident cases among 2,180 participants in the lenacapavir group (incidence 0.10 per 100 person-years); 99.9% of participants did not acquire HIV in the lenacapavir group. The results demonstrated superiority of twice-yearly lenacapavir over bHIV (incidence 2.37 per 100 person-years), with 96% relative risk reduction (incidence rate ratio 0.04, p<0.0001). There were 9 incident cases among 1,087 individuals in the Truvada group (incidence 0.93 per 100 person-years). Twice-yearly lenacapavir was 89% more effective than once-daily Truvada (incidence rate ratio 0.11, p=0.00245). In the trial, lenacapavir and Truvada were generally well-tolerated and no significant or new safety concerns were identified.

“The difficulty some people can experience with taking an oral pill every day, including challenges with adherence and stigma, have hindered uptake and persistence of the standard of care for too long, thus blunting PrEP’s impact on HIV prevention,” said PURPOSE 2 Principal Investigator Onyema Ogbuagu, MBBCh, FACP, FIDSA, Associate Professor of Medicine and Pharmacology at Yale School of Medicine and Director of the Yale Antivirals and Vaccines Research Program. “The incredible efficacy demonstrated in the PURPOSE 2 trial, the potential benefits of a twice-yearly injection, and the diversity of trial sites and participants show the impact that lenacapavir for PrEP could have for people around the world who need new choices to reduce their chances of acquiring HIV. This breakthrough adds significantly to our arsenal of tools to move us closer to achieving an AIDS-free generation.”

“In the United States, the stubbornly high rate of HIV diagnoses—especially in the U.S. South, and particularly among gay and bisexual men of color and transgender people—demands novel approaches to help people prevent HIV acquisition,” said Colleen Kelley, MD, MPH, Professor of Medicine at Emory University and a PURPOSE 2 Principal Investigator. “Because adherence to oral products can be challenging for some people, twice-yearly injectable lenacapavir for PrEP has the potential to be one of the most impactful interventions we could have to drive down new infections and bring us closer to ending the HIV epidemic in the United States.”

The use of lenacapavir for the prevention of HIV is investigational and has not been determined to be safe or efficacious and is not approved anywhere globally.

There is currently no cure for HIV or AIDS.