FDA approves twice-yearly lenacapavir PrEP

The federal Food and Drug Administration on Wednesday approved twice-yearly lenacapavir PrEP, the longest-acting HIV prevention method. While advocates lauded the eagerly anticipated approval, they expressed concern that the $28,000 annual price tag could limit availability as HIV prevention funding is being slashed in the U.S. and worldwide.

“This long-acting injectable PrEP option could be a game-changer in HIV prevention,” Dr. Hyman Scott, medical director of the San Francisco AIDS Foundation, told the Bay Area Reporter. However, if the cost is too high, “it won’t be accessible and affordable for all who want it. At a time when HIV prevention is deprioritized by the federal government, no-cost coverage for preventive medications is at risk, and HIV research is in jeopardy, we need these new preventive tools more than ever.”

Lenacapavir, the first HIV capsid inhibitor, is an antiretroviral drug that blocks viral replication. It was approved in 2022 under the brand name Sunlenca for the treatment of multidrug-resistant HIV. Lenacapavir for PrEP got a new brand name, Yeztugo, and a price reduction from $42,000 per year. Lenacapavir is not a vaccine that trains the immune system to fight the virus, but after all traditional HIV vaccine candidates have failed, long-acting PrEP is the next best thing. Yeztugo is made by Gilead Sciences Inc.

The June 18 approval comes 13 years after the FDA approved the first PrEP option, Gilead’s once-daily Truvada pill (tenofovir disoproxil fumarate/emtricitabine). Before Wednesday, ViiV Healthcare’s Apretude (injectable cabotegravir), which is administered every other month, was the longest-acting PrEP option.

Yet biomedical HIV prevention has still not reached its full potential. Only around a third of the 1.2 million people who could benefit from PrEP are using it, according to the Centers for Disease Control and Prevention. Clinicians and advocates are hopeful that a twice-yearly option could help close the gap.

“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,” Dr. Carlos del Rio of Emory University School of Medicine, stated in a Gilead news 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.”

The approval is supported by two large studies showing that lenacapavir PrEP dramatically reduced HIV acquisition in groups at high risk. As the B.A.R. previously reported, results from the PURPOSE 1 trial , first presented at the 2024 International AIDS Conference, showed that lenacapavir injections every six months were 100% effective for young cisgender women in Africa. The injections significantly reduced HIV incidence compared with the background rate and were superior to daily Truvada,

Likewise, the PURPOSE 2 study , presented at the HIV Research for Prevention Conference last October, showed that twice-yearly lenacapavir injections reduced the risk of HIV acquisition by 96% relative to the background rate and by 89% compared to Truvada for gay and bisexual men and gender-diverse people in the United States and six other countries. In both trials, lenacapavir was safe and generally well-tolerated.

“The FDA approval of lenacapavir is a fitting culmination of a long journey of drug discovery and development,” said PURPOSE-2 investigator Onyema Ogbuagu, an infectious disease physician at the Yale School of Medicine. “The excellent results we observed with twice-yearly lenacapavir provide renewed optimism about how far we could go with our new biomedical tools to achieve greater uptake of HIV prevention to help us move closer to ending the HIV epidemic.”

Access is key
To have a real impact, however, advocates and health officials stress that long-acting PrEP must be widely available and affordable to those who need it most in the U.S. and worldwide.

In a statement to the B.A.R., Gilead said its access strategy for lenacapavir PrEP in the U.S. “is designed to enable broad uptake and availability for individuals with and without insurance coverage.”

Under the Affordable Care Act, insurers are required to cover recommended prevention services at no charge, but the U.S. Supreme Court is now considering a legal challenge lodged by conservative businesses that object to PrEP coverage on religious grounds. A decision in the Braidwood case is expected later this month.

The Trump administration’s proposed budget decimates funding for HIV prevention services – particularly those targeting higher-risk groups such as Black and Latino gay men and transgender women – which would hamper HIV testing and PrEP provision. Deep cuts to Medicaid in the proposed House and Senate budgets are also a concern, as some 40% of people with HIV rely on the public insurance program.

“The FDA’s approval of lenacapavir for HIV prevention has the potential to be a pivotal moment for the broader fight to end HIV,” Maxx Boykin, manager of the Save HIV Funding campaign, said in a statement . “It’s a reminder that prevention must be a national priority, backed by serious investment and political will. Ending the epidemic requires equal focus on prevention and treatment, delivered through equitable, community-driven systems. This moment calls for bold public funding, strong private sector leadership, and a shared commitment to making HIV prevention accessible, affordable, and a cornerstone of our national response.”

At the global level, lenacapavir access is threatened by cuts to PEPFAR, the President's Emergency Plan for AIDS Relief, which for years has been the largest funder of PrEP worldwide. Although Secretary of State Marco Rubio has said that HIV treatment funding would continue, the status of prevention services is unclear .

“The approval of lenacapavir is a much-needed boost for HIV prevention, given the strength of the science and the simultaneous disruption in HIV programs globally,” Mitchell Warren, executive director of AVAC, said in a statement . “Scientific progress only matters if innovation actually reaches people. Lenacapavir for PrEP is poised to re-shape the HIV response, but only if today’s approval is accompanied by bold, strategic, effective and equitable rollout that reaches the populations that need access.”

Gilead announced last year that it will work with pharmaceutical manufacturers to offer generic versions of lenacapavir in more than 100 resource-limited countries and will provide the drug before generic manufacturers are up and running in 18 countries with high HIV rates. A study found that the price of lenacapavir could be brought down to around $40 per year with voluntary licensing and competition between generic suppliers. But advocates contend that middle-income countries such as Brazil – one of the countries where PURPOSE-2 was conducted – also need access to lenacapavir PrEP at a lower cost.

“Lenacapavir could be the tool we need to bring new infections under control – but only if it is priced affordably and made available to everyone who could benefit,” UNAIDS Executive Director Winnie Byanyima said in a statement . “If this game-changing medicine remains unaffordable, it will change nothing. I urge Gilead to do the right thing. Drop the price, expand production, and ensure the world has a shot at ending AIDS.”