Key Takeaways
- Twice-yearly pre-exposure prophylaxis (PrEP) shows strong efficacy: Yeztugo prevented HIV infections in pregnant women and young people across both PURPOSE 1 and PURPOSE 2 Phase III clinical trials.
- High patient preference for injectable PrEP: Over 75% of participants favored twice-yearly injections over daily oral medication, citing better adherence and confidence.
- Global regulatory expansion underway: Following FDA approval, Gilead has submitted applications for Yeztugo in regions including Europe, South America, and Africa.
Results from the Phase III PURPOSE 1 (NCT04994509) and PURPOSE 2 (NCT04925752) trials show that Gilead’s twice-yearly pre-exposure prophylaxis (PrEP) Yeztugo (lenacapavir) is highly effective and well tolerated across a broad spectrum of populations traditionally underrepresented in HIV prevention research. These populations include pregnant and lactating women, adolescents, and young adults, as well as individuals with coexisting conditions such as tuberculosis.1
Is Twice-Yearly Yeztugo the Breakthrough PrEP Option for Underserved Populations?
“It’s a thrill to be back in Kigali with so many of the community, advocacy and research partners who helped make PURPOSE the most intentionally inclusive HIV prevention trial program ever conducted,” said Moupali Das, VP, clinical development, HIV prevention & pediatrics, Gilead Sciences, in a press release. “As the first and only twice-yearly PrEP option, Yeztugo continues to demonstrate efficacy and tolerability among diverse populations, and we’re excited to highlight new data on this breakthrough HIV prevention option here at IAS 2025.”
PURPOSE 1 Trial Design and Patient Population
- The double-blind, multicenter, randomized PURPOSE 1 trial evaluated the efficacy of Yeztugo and emtricitabine/tenofovir alafenamide in preventing HIV infection in approximately 5,368 adolescent girls and young women.
- The dual primary endpoints of the trial were the recent infection testing algorithm estimate of the background HIV incidence rate per 100 person-years and the HIV incidence per 100 person-years in the treatment group compared to screened participants.2
PURPOSE 2 Trial Design and Patient Population
- The double-blind, multicenter, randomized PURPOSE 2 trial evaluated the safety and efficacy of subcutaneous twice-yearly Yeztugo PrEP in 3,295 cisgender men, transgender women, transgender men, and gender nonbinary people ≥16 years of age who have sex with male partners and are at risk for HIV infection.
- The dual primary endpoints of the trial were background HIV incidence per 100 person-years and the number of participants with an HIV diagnosis.
- Key secondary endpoints included the number of participants diagnosed with HIV while adherent to treatment, the percentage of participants experiencing treatment-emergent adverse events (AEs), and the percentage of participants experiencing clinically significant laboratory abnormalities.3
Strong Protection Seen in Pregnant Women and Young People Across Both Trials
- Results from PURPOSE 1 show that there were no new HIV infections among the 184 pregnant or breastfeeding patients who received Yeztugo.
- There were also no infections reported in patients aged 16 to 25 years who were treated with Yeztugo.
- Results from PURPOSE 2 showed that only two HIV infections were reported in patients aged 16 to 25 years.
- Across both trials, over 75% of participants preferred twice-yearly injections over daily oral PrEP.
- Yeztugo was well tolerated in both trials, with no new safety signals identified in any of the observed populations.
- Common AEs included injection site reactions, headache, and nausea.
Global Filings Follow FDA Approval
The new data comes nearly a month after Yeztugo was approved as the first and only twice-yearly injectable option for HIV PrEP in adults and adolescents weighing at least 77 lbs. According to Gilead, regulatory filings are also underway in multiple countries across Europe, South America, and Africa.4
“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,” said Carlos del Rio, MD, distinguished professor of medicine, dvision of infectious diseases, Emory University School of Medicine, co-director, Emory Center for AIDS Research in Atlanta, in a June press release. “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.”4
References
- Gilead Presents New Data on Twice-Yearly Lenacapavir (Yeztugo®) for HIV Prevention at IAS 2025. Gilead. July 14, 2025. Accessed July 17, 2025. https://www.gilead.com/news/news-details/2025/gilead-presents-new-data-on-twice-yearly-lenacapavir-yeztugo-for-hiv-prevention-at-ias-2025
- Pre-Exposure Prophylaxis Study of Lenacapavir and Emtricitabine/Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV Infection (PURPOSE 1). Clinicaltrials.gov. Accessed July 17, 2025. https://clinicaltrials.gov/study/NCT04994509
- Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection (PURPOSE 2). Clinicaltrials.gov. Accessed July 17, 2025. https://clinicaltrials.gov/study/NCT04925752?cond=hiv&term=purpose%202&rank=1
- FDA Approves Gilead’s Yeztugo as First Twice-Yearly Injection for HIV Pre-Exposure Prophylaxis. PharmExec. June 19, 2025. Accessed July 17, 2025. https://www.pharmexec.com/view/fda-approves-gilead-yeztugo-first-twice-yearly-injection-hiv-pre-exposure-prophylaxis
