Gilead encouraged by data on once-yearly lenacapavir for HIV prevention
Key takeaways:
- Two formulations of once-yearly injectable lenacapavir for PrEP were safe, well tolerated and generated appropriate blood levels of the drug.
- Gilead said it plans to start phase 3 trials later this year.
SAN FRANCISCO — New data suggest that lenacapavir delivered just once per year could be as effective for HIV prevention as the twice-yearly injections already under review by the FDA.
Gilead Sciences presented data from a phase 1 study of once-a-year lenacapavir for HIV PrEP at the Conference on Retroviruses and Opportunistic Infections and published the results simultaneously in The Lancet.
The study showed that either of the two new formulations of the drug could be effective, allowing people to receive the drug just once per year instead of twice.
“What we found is that the ... blood levels of these formulations were higher than twice-yearly subcutaneous lenacapavir,” Renu Singh, PhD, MS, senior director and clinical pharmacologist at Gilead, told Healio.
It means once-yearly lenacapavir “can provide similar levels of high efficacy as we have seen with twice-yearly subcutaneous lenacapavir,” Singh said. “Both formulations were safe and well tolerated, and with these encouraging results we plan to initiate phase 3 studies later this year.”
Lenacapavir is already approved for use in the United States for the treatment of resistant HIV. The FDA has scheduled a June deadline to consider Gilead’s application to market lenacapavir as a twice-yearly injectable for PrEP based on the results of two phase 3 trials, PURPOSE 1 and PURPOSE 2. Experts have heralded the drug as a potential breakthrough in HIV prevention.
In an ongoing, open-label phase 1 trial, Singh and colleagues evaluated two intramuscular formulations containing a 5,000 mg dose of lenacapavir — one containing 5% ethanol and another containing 10% ethanol — among 40 adults aged 18 to 55 years assigned in a 1:1 ratio to each formulation. (Twice-yearly lenacapavir consists of 927 mg of the drug delivered in two injections every 26 weeks.)
The researchers evaluated the safety and tolerability of the injections among participants and assessed the pharmacokinetics (PK) and safety from days 1 through 15 after injection and collected single anytime PK samples through day 449 of the trial. They measured the PK samples for maximum observed concentration and trough concentration.
According to Gilead’s summary of the data, plasma concentrations for once-yearly lenacapavir “remained above the 95% effective concentration for at least 56 weeks with both formulations,” and the median trough concentrations of both formulations after 1 year were higher than they were in the two PURPOSE trials through 16 weeks.
Additionally, participants in the two groups experienced similar levels and severity of adverse events, including injection-site reactions and mild pain.
“As a clinical pharmacologist, it gives me great pleasure to see a small molecule last this long,” Singh said. “It has never been done before, so I’m really thrilled about these data. Overall, these results indicate that once-annual lenacapavir has the potential to provide significantly high efficacy.”
References:
- First clinical data for Gilead’s investigational once-yearly lenacapavir for HIV prevention presented at CROI 2025 and published in The Lancet. https://www.gilead.com/news/news-details/2025/first-clinical-data-for-gileads-investigational-once-yearly-lenacapavir-for-hiv-prevention-presented-at-croi-2025-and-published-in-the-lancet. Published March 11, 2025. Accessed March 14, 2025.
- Singh R, et al. Abstract 154. Presented at: Conference on Retroviruses and Opportunistic Infections; March 9-12, 2025; San Francisco.
- Singh R, et al. The Lancet. 2025;doi:10.1016/S0140-6736(25)00405-2.
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Singh R, et al. Abstract 154. Presented at: Conference on Retroviruses and Opportunistic Infections; March 9-12, 2025; San Francisco.
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