FDA Approves Lenacapavir, First Twice-Yearly HIV Prevention Option

On this day, June 18, 2025, the FDA has approved lenacapavir (Gilead) under the name Yeztugo, an injectable HIV-1 capsid inhibitor, as pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV in adults and adolescents weighing at least 35kg.1

The medication is the first twice-yearly option for preventing HIV to be approved and significantly improves the treatment burden on patients compared to current daily oral (Gilead's Truvada and Descovy) or bimonthly injectable (GSK's Apretude) options.2

It was previously approved as a method of antiretroviral therapy in December 2022 for patients with limited options for treatment due to treatment resistance, safety, or intolerance.3

“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 Chief Executive Officer of Gilead Sciences, said in a statement.1 “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. Gilead scientists have made it their life’s work to end HIV and now, with the FDA approval of Yeztugo and in collaboration with our many partners, we can help to make that goal a reality.”

The FDA approval was based off of data from the phase 3 PURPOSE 1 and PURPOSE 2 trials. In PURPOSE 1, 5338 cisgender women from South Africa and Uganda were randomized in a 2:2:1 ratio to receive either lenacapavir twice per year, daily oral emtricitabine-tenofovir alafenamide (F/TAF), or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF).4 No participants in the lenacapavir group had contracted HIV by the end of the trial compared with 39 in the F/TAF group and 16 in the F/TDF group, in which adherence was also low. Patients in the lenacapavir group reported more injection site reactions compared with the placebo groups (68.8% vs 34.9%), and 0.2% of the participants in the lenacapavir group discontinued the treatment due to these reactions.

In PURPOSE 2, in 3265 men and gender-diverse individuals, including transgender women, transgender men, and gender nonbinary individuals, investigators found that 2 individuals in the lenacapavir group had contracted the virus compared with 9 in the F/TDF group. No notable safety concerns were identified but 1.2% of the lenacapavir group did discontinue the treatment due to injection site reactions.5

“Yeztugo could be the transformative PrEP option we’ve been waiting for—offering the potential to boost PrEP uptake and persistence and adding a powerful new tool in our mission to end the HIV epidemic,” Carlos del Rio, MD, Distinguished Professor of Medicine in the Division of Infectious Diseases at Emory University School of Medicine and Co-Director of the Emory Center for AIDS Research in Atlanta, added.2 “A twice-yearly injection could greatly address key barriers like adherence and stigma, which individuals on more frequent PrEP dosing regimens, especially daily oral PrEP, can face. We also know that, in research, many people who need or want PrEP preferred less frequent dosing.”

Notably, Gilead has stated its intent to supply lenacapavir to low-income countries despite funding for overseas HIV aid being reduced significantly by the Trump administration, although time will tell how affordable and accessible lenacapavir proves to be in the US and beyond.6

REFERENCES

1. Yeztugo® (Lenacapavir) Is Now the First and Only FDA-Approved HIV Prevention Option Offering 6 Months of Protection. News release. Gilead. June 18, 2025. https://www.businesswire.com/news/home/20250520465880/en/Yeztugo-Lenacapavir-Is-Now-the-First-and-Only-FDA-Approved-HIV-Prevention-Option-Offering-6-Months-of-Protection
2. Pre-Exposure Prophylaxis (PrEP). Webpage. NIH. April 9, 2025. https://hivinfo.nih.gov/understanding-hiv/fact-sheets/pre-exposure-prophylaxis-prep
3. Sunlenca® (lenacapavir) Receives FDA Approval as a First-in-Class, Twice-Yearly Treatment Option for People Living With Multi-Drug Resistant HIV. News Release. Gilead. December 22, 2022. https://www.gilead.com/news/news-details/2022/sunlenca-lenacapavir-receives-fda-approval-as-a-first-in-class-twice-yearly-treatment-option-for-people-living-with-multi-drug-resistant-hiv
4. Bekker LG, Das M, Karim QA, et al. Twice-yearly lenacapavir or daily F/TAF for HIV prevention in cisgender women. N Engl J Med. 2024;391:1179-1192. doi:10.1056/NEJMoa2407001
5. 5. Kelley CF, Acevedo-Quiñones M, Agwu AL, et al. Twice-yearly lenacapavir for HIV prevention in men and gender-diverse persons. N Engl J Med. 2025;392:1261-1276 doi:10.1056/NEJMoa2411858
6. Steenhuysen J, Beasley D. Gilead commits to HIV prevention rollout for low-income countries despite funding uncertainty. Reuters. May 30, 2025. Accessed June 13, 2025. https://www.reuters.com/business/healthcare-pharmaceuticals/gilead-commits-hiv-prevention-rollout-low-income-countries-despite-funding-2025-05-30/