Gilead presented the data at the Conference on Retroviruses and Opportunistic Infections (CROI 2025). Image credit: Shutterstock / Sundry Photography
Gilead is set to launch a Phase III trial of its once-yearly lenacapavir pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) following the success of a Phase I study.
The Phase I trial investigated two single 5,000mg doses of the yearly injection in 40 healthy participants at low risk of acquiring HIV. One formula contained 5% ethanol, the second contained 10% ethanol. Both groups achieved and maintained plasma concentrations above the 95% efficacy threshold for 56 weeks.
The data, presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2025) as well as in The Lancet, showed lenacapavir plasma trough concentrations for both formulations of once-yearly lenacapavir at week 52, 57.0ng/mL and 65.6ng/mL, were higher than those from twice-yearly lenacapavir in the Purpose 1 and Purpose 2 trials (NCT04994509 and NCT04925752) after 26 weeks, an average of 23.4ng/mL.
The Purpose 1 programme saw 100% prevention of HIV cases while Purpose 2 showed a 99.9% prevention in lenacapavir-treated patients. Twice-yearly lenacapavir is currently under priority review by the US Food and Drug Administration (FDA) with a decision expected by June 19.
The most common adverse event (AE) for both cohorts was injection site pain, which was mostly mild in severity and resolved within one week. Medication-emergent AEs were similar between the two cohorts and mostly mild to moderate in severity.
The study was designed to evaluate the safety and pharmacokinetics (PK) of the therapy. Participants had to be found to be negative for HIV prior to the trial.
Data from the trial confirmed that both once-yearly formulations of lenacapavir warrant further investigation, according to Gilead, with the company set to launch Phase III trials of the therapy in the second half of 2025.
Gilead Sciences’s senior vice president and virology therapeutic area head Dr Jared Baeten said: “Gilead is continuing to innovate in our work to develop additional person-centered long-acting injectable and oral options to help people find an HIV prevention choice that is right for them. Once-yearly lenacapavir, if approved, could become an important new HIV prevention option that could help address PrEP adherence and persistence challenges for individuals who need or want PrEP around the world.”
More data from Purpose
Alongside its Phase III plans, Gilead also presented more data from its Purpose clinical programme at the California conference. This included data from adolescents, aged 16 and 17 who were enrolled in the Purpose 1 study, with lenacapavir plasma concentrations being comparable between adolescent and adult trial groups.
The therapy was also able to show 100% no incidence of HIV infections across the adolescent group, the same as the adult group in the same study. Participants in both groups experienced the same most common AEs. Gilead now intends to submit data to agencies to support the use of twice-yearly lenacapavir in adolescents.
Gilead also revealed quantitative and qualitative survey data from the Purpose 1 trial, with approximately two-thirds of survey respondents preferring twice-yearly lenacapavir compared to once-daily pills. Additionally, 61% of respondents reported they would feel more protected from HIV with twice-yearly PrEP injections compared with once-daily pills, and 61% of respondents also reported they would feel more confident about not missing a PrEP dose with twice-yearly injections.
A need for less frequent PrEP
According to UNAIDS, 39.9 million people globally were living with HIV in 2023, with 1.3 million new infections in the same year.
After Gilead presented the flagship Purpose trial data, UNAIDS executive director Winnie Byanyima called upon Gilead Sciences to make twice-yearly lenacapavir available to people from developing countries. Byanyima said that people in Africa could be “freed from the stigma and fear of being attacked” that they face if they are seen swallowing tablets.
Gilead responded by stating it had provided royalty-free voluntary licensing agreements with six generic manufacturers to increase access to lenacapavir for HIV prevention in high-incidence, resource-limited countries.
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