Gilead's Twice-Yearly Lenacapavir Prevents HIV Better Than Daily Truvada: 96% Reduction in Infections in Phase 3 Trial

Gilead Sciences, Inc. has announced interim results from a pivotal Phase 3 clinical trial assessing lenacapavir, an injectable HIV-1 capsid inhibitor administered biannually. The data shows lenacapavir reduces HIV infections by 96% compared to background HIV incidence (bHIV). The study, named PURPOSE 2, included 2,180 participants, with only two new HIV cases reported, corresponding to a 99.9% non-acquisition rate in the lenacapavir group. Moreover, lenacapavir proved superior to the once-daily regimen of Truvada® (emtricitabine and tenofovir disoproxil fumarate).

PURPOSE 2 encompasses cisgender and transgender men and women, as well as gender non-binary individuals from Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States, who have sex with men. The independent Data Monitoring Committee (DMC) confirmed that the trial met its primary endpoint of lenacapavir’s superiority over bHIV and its secondary endpoint over Truvada for pre-exposure prophylaxis (PrEP). Consequently, the DMC recommended transitioning the trial to an open-label phase, offering lenacapavir to all participants.

Daniel O’Day, Chairman and CEO of Gilead, highlighted the potential of lenacapavir to transform HIV prevention and contribute to ending the epidemic. Gilead is preparing to collaborate with regulatory, government, public health, and community partners to ensure the global availability of lenacapavir for PrEP, pending approval.

This trial follows the PURPOSE 1 study, which in June 2024 also demonstrated lenacapavir’s efficacy for PrEP among cisgender women in sub-Saharan Africa. Data from both trials will support regulatory filings with the aim to make lenacapavir available to diverse populations globally. Gilead plans to initiate global regulatory submissions by late 2024, aiming for an initial launch in 2025.

Gilead is prioritizing rapid access and efficient regulatory approval processes for lenacapavir in high-incidence, low-resource countries. The company is committed to making lenacapavir accessible in these regions, including via expedited voluntary licensing agreements for affordable versions of the drug.

PURPOSE 2 is a rigorous double-blind, multicenter, randomized study involving over 3,200 participants aged 16 and older. Participants, recruited from 88 sites across seven countries, were randomized in a 2:1 ratio to receive either lenacapavir or Truvada. Due to ethical considerations, a placebo group was not included; instead, bHIV served as the primary comparator.

The trial results indicated a 0.10 per 100 person-years HIV incidence in the lenacapavir group, with a 96% relative risk reduction compared to bHIV (2.37 per 100 person-years). The lenacapavir group reported only two new HIV cases among 2,180 participants, while the Truvada group had nine cases among 1,087 participants (0.93 per 100 person-years), showing lenacapavir’s 89% higher efficacy. Both treatments were well-tolerated, with no new or significant safety concerns.

The results underscore the potential of lenacapavir to significantly impact HIV prevention. Onyema Ogbuagu, a Principal Investigator for PURPOSE 2, emphasized the importance of lenacapavir’s biannual injection for improving adherence and reducing stigma associated with daily oral PrEP.

In the U.S., the persistent high rates of HIV, especially in the South and among marginalized groups, highlight the need for innovative prevention methods. Colleen Kelley, another Principal Investigator, pointed out the potential of twice-yearly lenacapavir to reduce new infections significantly.

Lenacapavir is currently under investigation for HIV prevention, with its safety and efficacy yet to be established for this use. Gilead’s PURPOSE program, the most comprehensive HIV prevention trial initiative, assesses lenacapavir’s potential across diverse populations worldwide.

Lenacapavir, already approved for treating multi-drug resistant HIV in combination with other antiretrovirals, is designed to inhibit HIV at multiple lifecycle stages. Gilead continues to explore lenacapavir as a long-acting option for future HIV therapies, aiming to offer flexible dosing regimens that meet the needs of diverse populations.

For more than three decades, Gilead has been at the forefront of HIV research and treatment, pioneering several breakthroughs. The company remains committed to advancing HIV prevention and care through continued scientific innovation and global partnerships to address the evolving needs of people affected by HIV.

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