FDA Approves Twice-Yearly Lenacapavir for HIV Preexposure Prophylaxis

The FDA has approved lenacapavir (Yeztugo; Gilead Sciences), a twice-yearly injectable HIV-1 capsid inhibitor, for the prevention of HIV as preexposure prophylaxis (PrEP), according to reports from NBC News, USA Today, and CNBC and a news release from Gilead Sciences.^1-4

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“This is a historic day in the decades-long fight against HIV. Yeztugo is one of the most important scientific breakthroughs of our time and offers a very real opportunity to help end the HIV epidemic,” Daniel O’Day, chairman and CEO of Gilead Sciences, said in a news release. “This is a medicine that only needs to be given twice a year and has shown remarkable outcomes in clinical studies, which means it could transform HIV prevention."⁴

Data from pivotal phase 3 trials provided the backing for this approval. In PURPOSE 1 (NCT04994509), lenacapavir was found to be highly effective among trial participants, with 0 HIV infections observed in the lenacapavir group (0/100 person-years; 95% CI, 0.00–0.19) compared with background HIV incidence, which translated to a 100% reduction in HIV infections.^5,6

Investigators of PURPOSE 2 (NCT04925752) found that lenacapavir was highly effective at reducing HIV infections among trial enrollees, with 99.9% of participants treated with lenacapavir not acquiring HIV infection in the trial, despite the high reported levels of sexual behavior and sexually transmitted infections observed among trial participants.^7,8

In both PURPOSE 1 and 2, patients were highly adherent to lenacapavir injections. At week 26, 91.5% and 91.0% of participants from the respective trials received on-time injections, and at 1 year, these rates were each 92.8%. With lenacapavir only necessitating injections twice-yearly, it now serves as one of the most convenient and effective HIV treatment options available to patients.^5,7

Based on these positive trial results, the FDA accepted lenacapavir new drug applications for priority review in early 2025, which followed a breakthrough therapy designation granted by the FDA in October 2024. These processes allowed for lenacapavir to have an expedited review process due to the substantial improvements it could make compared with currently available therapies.⁹

Lenacapavir was originally developed as a therapy for adults living with HIV who harbored infections resistant or intolerant to available treatments or for whom safety considerations prevented using other PrEP options. In 2022, it received approval from the FDA for patients with HIV-1 infection in heavily treatment-experienced (HTE) adults with multi-drug resistant (MDR) infection.^10,11

REFERENCES

1. Ryan B. FDA approves powerful HIV drug that nearly eliminated spread in clinical trials. NBC News. June 18, 2025. Accessed June 18, 2025. https://www.nbcnews.com/health/health-news/fda-hiv-prevention-drug-prep-lenacapavir-rcna208387

2. Alltucker K. FDA approves new twice-yearly HIV shot. What to know. June 18, 2025. Accessed June 18, 2025. https://www.usatoday.com/story/news/health/2025/06/18/hiv-epidemic-new-shot-fda-approval/84240744007/

3. Constantino AK. FDA approves Gilead’s twice-yearly HIV prevention injection, offering a powerful and convenient new option. CNBC. June 18, 2025. Accessed June 18, 2025. https://www.cnbc.com/2025/06/18/fda-approves-gilead-hiv-prevention-injection-lenacapavir.html

4. Gilead Sciences. Yeztugo® (Lenacapavir) Is Now the First and Only FDA-Approved HIV Prevention Option Offering 6 Months of Protection. News Release. Released June 18, 2025. Accessed June 18, 2025. https://www.gilead.com/news/news-details/2025/yeztugo-lenacapavir-is-now-the-first-and-only-fda-approved-hiv-prevention-option-offering-6-months-of-protection

5. Gilead Sciences. Full Efficacy and Safety Results for Gilead Investigational Twice-Yearly Lenacapavir for HIV Prevention Presented at AIDS 2024. News Release. July 24, 2024. Accessed June 6, 2025. https://www.gilead.com/news/news-details/2024/full-efficacy-and-safety-results-for-gilead-investigational-twice-yearly-lenacapavir-for-hiv-prevention-presented-at-aids-2024

6. Pre-Exposure Prophylaxis Study of Lenacapavir and Emtricitabine/​Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV Infection (PURPOSE 1). National Library of Medicine. ClinicalTrials.gov Identifier: NCT04994509. Updated February 24, 2025. Accessed June 6, 2025. https://clinicaltrials.gov/study/NCT04994509

7. Gilead Sciences. Gilead Presents Full PURPOSE 2 Data Results for Twice-Yearly Lenacapavir for HIV Prevention at HIV Glasgow. News Release. November 13, 2024. Accessed June 6, 2025. https://www.gilead.com/news/news-details/2024/gilead-presents-full-purpose-2-data-results-for-twice-yearly-lenacapavir-for-hiv-prevention-at-hiv-glasgow

8. Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection (PURPOSE 2). National Library of Medicine. ClinicalTrials.gov Identifier: NCT04925752. Updated December 20, 2024. Accessed June 6, 2025. https://clinicaltrials.gov/study/NCT04925752

9. Gilead Sciences. U.S. FDA Accepts Gilead’s New Drug Applications for Twice-Yearly Lenacapavir for HIV Prevention Under Priority Review. News Release. February 18, 2025. Accessed June 6, 2025.

10. Parkinson J. The evolution of lenacapavir in HIV treatment. ContagionLive. Updated July 25, 2024. Accessed June 6, 2025. https://www.contagionlive.com/view/the-evolution-of-lenacapavir

11. Gilead Sciences. Suleca (lenacapavir) Receives FDA Approval as a First-in-Class, Twice-Yearly Treatment Option for People Living With Multi-Drug Resistant HIV. News Release. December 22, 2022. Accessed June 6, 2025.