Gilead’s HIV-1 capsid inhibitor, which is a twice-yearly injection, was more effective than a daily Truvada pill in a phase 3 trial.
Gilead released data from its PURPOSE 2 trial looking at lenacapavir for PrEP.
Gilead announced today that its twice-yearly injectable HIV capsid inhibitor, lenacapavir (Sunlenca), was more efficacious in preventing HIV infection than a daily PrEP pill, emtricitabine and tenofovir disoproxil (Truvada).
Early data was shared from the PURPOSE 2 phase 3 clinical trial. The investigators reported there were 2 confirmed cases of HIV among 2,180 participants in the lenacapavir group (incidence 0.10 per 100 person-years); thus demonstrating a 99.9% prevention rate amongst participants. 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). 1
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).1
“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,” 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.1
In the PURPOSE 2 phase 3 trial, lenacapavir, a twice-yearly injectable, was found to be 96% more effective than the standard PrEP pill, Truvada, in preventing HIV infections.
The trial included a diverse group of participants across multiple countries and genders, highlighting the potential global impact of lenacapavir.
Gilead is committed to making lenacapavir accessible, especially in high-incidence, low-resource regions.
The second trial, PURPOSE 2, 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 bHIV (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.1
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.1
Both lenacapavir and Truvada were generally well-tolerated and no significant or new safety concerns were identified.1
This is the second phase 3 trial to demonstrate superior efficacy for twice-yearly lenacapavir for the investigational use of HIV prevention as PrEP. In June 2024, the first study, aptly named, PURPOSE 1 trial, which studied lenacapavir for PrEP among cisgender women in sub-Saharan Africa, demonstrated 100% efficacy in preventing HIV infection among participants. The trial encompassed over 5,300 participants across South Africa and Uganda.2
“With such remarkable outcomes across 2 phase 3 studies, lenacapavir has demonstrated the potential to transform the prevention of HIV and help to end the epidemic,” said Gilead CEO Daniel O'Day in a statement.1
The question of access to lenacapavir was brought up during the International AIDS Society 2024 conference in July, especially in areas of need and those low and middle income countries.
In today’s press statement, the company looked to address that.
“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.”1
Gilead said it plans to continue its pursuit of regulatory approvals. “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,” said O’Day.
