HIV Infections Significantly Reduced With Twice-Yearly Lenacapavir in Cisgender Men, Gender-Diverse Participants

These results build off the PURPOSE 1 trial, contributing to the wealth of evidence surrounding lenacapavir’s positive effects in patients with HIV.

According to results from the pivotal PURPOSE 2 (NCT04925752) phase 3 clinical trial, twice-yearly injectable lenacapavir (Sunlenca; Gilead Sciences Inc), an HIV-1 capsid inhibitor, reduced HIV infections by 96% compared to background HIV incidence (bHIV), demonstrating superiority to the emtricitabine and tenofovir disoproxil fumarate combination (Truvada; Gilead Sciences Inc).^1,3

Image credit: © Yang MingQi | stock.adobe.com

The announcement, published in a news release from Gilead, marks the second phase 3 trial investigating lenacapavir. The first, the results of which were published in July 2024, specifically examined HIV incidence in cisgender women in sub-saharan Africa after treatment with lenacapavir. Investigators found the inhibitor demonstrated 100% efficacy and superiority compared to background HIV incidence.^1,2

PURPOSE 2 met its key primary efficacy end points, according to the independent Data Monitoring Committee (DMC), determining superiority of twice-yearly lenacapavir to both bHIV and once-daily Truvada. Because the trial has met its end points, the DMC recommended to Gilead that the blinded phase of the trial be ceased and lenacapavir be offered to all participants.¹

“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,” Daniel O’Day, chairman and CEO of Gilead, said in the news release. “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.”¹

The PURPOSE 2 trial enrolled over 3200 cisgender men, transgender men, transgender women, and gender non-binary individuals aged 16 years or older who have sex with partners that were assigned male at birth. Participants were randomized to receive either lenacapavir or emtricitabine-tenofovir in a 2:1 ratio.¹

In the lenacapavir group, there were only 2 incident cases of HIV among 2180 participants, resulting in 99.9% of the participants not acquiring HIV. The investigators determined twice-yearly lenacapavir to be 89% more effective than once-daily emtricitabine-tenofovir (incidence rate ratio: 0.11, p = .00245). Importantly, both HIV drugs were generally well-tolerated among the participants, with no significant or new safety concerns.¹

About the Trial

Trial Name: Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection (PURPOSE 2)

ClinicalTrials.gov ID: NCT04925752

Sponsor: Gilead Sciences

Estimated Completion Date: August 2025

Positive data across both the PURPOSE 1 (NCT04994509) and PURPOSE 2 studies give Gilead a wealth of research to support upcoming regulatory filings. Gilead is seeking regulatory approval for lenacapavir to make the drug available to populations around the world who are the most in need for HIV prevention. The company aims to present additional data from PURPOSE 2 later this year.¹

Lenacapavir has been through the investigational process for many years to thoroughly assess its effectiveness in multiple areas. In July 2023, results from the phase 2/3 CAPELLA (NCT04150068) trial indicated favorable long-term outcomes in patients with HIV who were heavily treatment experienced. Given heavy treatment can negatively impact quality of life, these results were important to ensure that patients using lenacapavir did not face increased health burdens.⁴

Furthermore, the FDA has previously taken regulatory action involving lenacapavir, though it was aimed towards a very specific population. In December 2022, the agency approved the capsid inhibitor for adult patients with HIV-1 whose infections could not be effectively treated with other available treatments due to safety concerns, intolerance, or resistance.⁵

Building from these prior actions and the positive PURPOSE 1 and 2 results, lenacapavir looks to be on track for full regulatory approval worldwide soon.

REFERENCES

1. Gilead. Gilead’s twice-yearly lenacapavir for HIV prevention reduced HIV infections by 96% and demonstrated superiority to daily Truvada in second pivotal phase 3 trial. News Release. Released September 12, 2024. Accessed September 12, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2024/9/gileads-twiceyearly-lenacapavir-for-hiv-prevention-reduced-hiv-infections-by-96-and-demonstrated-superiority-to-daily-truvada-in-second-pivotal-ph

2. Halpern L. Twice-yearly lenacapavir effective in significantly reducing HIV infections in cisgender women. Pharmacy Times. Published July 25, 2024. Accessed September 12, 2024. https://www.pharmacytimes.com/view/twice-yearly-lenacapavir-effective-in-significantly-reducing-hiv-infections-in-cisgender-women

3. ClinicalTrials.gov. Study of lenacapavir for HIV pre-exposure prophylaxis in people who are at risk for HIV infection (PURPOSE 2). National Library of Medicine. Last updated July 12, 2024. Accessed September 12, 2024. https://clinicaltrials.gov/study/NCT04925752?cond=HIV&term=purpose%202&rank=1

4. Hunter E. Twice-yearly subcutaneous lenacapavir injection for HIV provides favorable quality-of-life outcomes. Pharmacy Times. Published July 27, 2023. Accessed September 12, 2024. https://www.pharmacytimes.com/view/twice-yearly-subcutaneous-lenacapavir-injection-for-hiv-provides-favorable-quality-of-life-outcomes

5. Hippensteele A. FDA approves HIV drug for adults who have not successfully responded to other available treatments. Pharmacy Times. Published December 22, 2022. Accessed September 12, 2024. https://www.pharmacytimes.com/view/fda-approves-hiv-drug-for-adults-who-have-not-successfully-responded-to-other-available-treatments