In a landmark decision, the U.S. Food and Drug Administration (FDA) on June 19, 2025, approved Gilead Sciences’ lenacapavir, the first twice-yearly injectable pre-exposure prophylaxis (PrEP) drug for HIV prevention. Branded as Yeztugo, the medication represents a significant advancement in the global effort to reduce new HIV infections and improve adherence to preventive therapy.
The approval follows a fast-tracked review process under the FDA’s Breakthrough Therapy and Priority Review designations, reflecting the drug’s transformative potential. Gilead had submitted its New Drug Application (NDA) in October 2024, and the Prescription Drug User Fee Act (PDUFA) target date had been set for June 19.
A New Era for HIV Prevention
Lenacapavir works by inhibiting the HIV capsid protein, effectively blocking the virus at multiple stages of its lifecycle. Administered just twice a year via subcutaneous injection, the treatment offers a much-needed alternative to daily oral medications like Truvada and Descovy, which, while effective, have long posed adherence challenges.
The approval was largely driven by outstanding results from two global Phase III trials—PURPOSE 1 and PURPOSE 2—which demonstrated nearly 100% efficacy in preventing HIV transmission among high-risk individuals. Notably, the PURPOSE 1 trial, which included cisgender women in sub-Saharan Africa, reported zero new HIV infections among participants receiving lenacapavir. In the PURPOSE 2 trial, which focused on men who have sex with men and transgender women, the efficacy rate exceeded 99%.
“These results are extraordinary and signal a major leap forward in our ability to curb the HIV epidemic,” said Dr. Linda-Gail Bekker, a South African infectious disease specialist who was involved in the PURPOSE studies.
Broader Implications for Public Health
The introduction of a long-acting injectable PrEP could be particularly beneficial in communities where stigma, access barriers, or logistical challenges have made daily pill-taking difficult. Advocates point out that fewer doses not only simplify adherence but also allow for more discreet and convenient prevention.
“This is a game changer,” said Carl Schmid, executive director of the HIV+Hepatitis Policy Institute. “Twice-yearly dosing has the potential to dramatically increase uptake and reduce disparities in HIV prevention, especially among underserved populations.”
In the U.S., the Centers for Disease Control and Prevention (CDC) estimates that more than 30,000 new HIV infections occur annually, despite the availability of daily PrEP. Uptake remains particularly low among Black and Latino communities, who are disproportionately affected by the virus. Experts hope lenacapavir can help close these gaps.
Access and Affordability
While the approval has been widely celebrated, concerns remain around pricing and equitable access. Yeztugo is expected to carry a list price exceeding $28,000 per year in the U.S. Gilead has stated it will work with public and private insurers to ensure broad access and will offer a patient assistance program to mitigate out-of-pocket costs.
Globally, Gilead has pledged to manufacture 10 million doses of lenacapavir by 2026 and has signed licensing agreements with generic manufacturers for distribution in 120 low- and middle-income countries. These deals are royalty-free, a move applauded by global health advocates, though they caution that sustained funding—through initiatives like PEPFAR and the Global Fund—is necessary to ensure the medication reaches those who need it most.
Looking Ahead
With FDA approval secured, Yeztugo will become available in the U.S. in the coming months, pending final payer negotiations. International regulatory bodies, including the European Medicines Agency (EMA) and the World Health Organization (WHO), are expected to follow with their own assessments later this year.
The arrival of lenacapavir signals not only a major milestone in HIV prevention but also a test of global commitment to equitable healthcare innovation. As the world marks more than four decades of battling HIV/AIDS, a twice-yearly injection may finally offer a scalable, sustainable tool to curb transmission and move closer to ending the epidemic.
