Gilead's Breakthrough Long-Acting HIV Prevention Therapy Yeztugo® Approved by FDA: Twice-Yearly Injection Demonstrates Near 100% Efficacy

Gilead Sciences announced on June 18, 2025, that the U.S. Food and Drug Administration (FDA) has approved its injectable HIV-1 capsid inhibitor, Yeztugo.^®(Lenapavir) as a pre-exposure prophylaxis (PrEP) drug to reduce the risk of HIV infection through sexual activity in adults and adolescents weighing 35 kilograms or more.

This marks Yeztugo^®Becoming the first and only PrEP option in the U.S. that requires dosing just twice a year. Study data showed that more than 99.9% of subjects receiving Yeztugo® remained HIV negative in the phase 3 clinical studies PURPOSE 1 and PURPOSE 2.

Yeztugo^®It is a "first-in-class" long-acting HIV capsid inhibitor that can interfere with the assembly and disassembly of HIV capsid proteins, acting at multiple stages of the viral life cycle. It has received Breakthrough Therapy Designation from the U.S. FDA for pre-exposure prophylaxis of HIV infection.

"This is a historic day in the decades-long fight against HIV. Yeztugo^®"It is one of the most important scientific breakthroughs of our time, truly providing us with an opportunity to help end HIV," said Daniel O’Day, Chairman and Chief Executive Officer of Gilead Sciences. "Yeztugo^®Only twice a year of administration has demonstrated outstanding results in clinical studies, which means it has the potential to revolutionize the prevention landscape of HIV. Scientists at Gilead Sciences have made it their lifelong mission to end HIV, and now, with the FDA approval of Yeztugo®, we will work closely with numerous partners to help achieve this goal."

The world's first PrEP drug was approved in the United States in 2012, also developed by Gilead Sciences. However, data from the U.S. Centers for Disease Control and Prevention (CDC) shows that in 2022 (the most recent year with available data), only about one-third (36%) of people in the U.S. who met the CDC's PrEP eligibility criteria had used PrEP medication.

AIDS is an infectious disease caused by HIV infection. The development of modern antiviral drugs and the rise of "cocktail therapy" have enabled patients with HIV infection to control their condition over the long term and achieve a life expectancy comparable to that of normal individuals. Recent studies have found that taking antiviral drugs before infection can reduce the risk of being infected with the HIV virus. This preventive therapy for HIV infection is called PrEP therapy.

CDC data shows that the PrEP usage rate among all populations in the U.S. has not yet reached a level sufficient to end HIV transmission at the population level, with significant gaps observed among women, Black/African American people, Hispanic/Latino populations, and individuals in the southern United States. The data also indicates that adherence challenges, stigma, and low awareness of PrEP among healthcare providers and consumers are barriers contributing to the low PrEP usage rates across multiple groups.

In 2023, more than 100 people in the United States are diagnosed with HIV every day, highlighting the potential impact of limited uptake, adherence, and accessibility.

“Yeztugo^®"It may be the transformative PrEP option we've been waiting for — it has the potential to increase the uptake and persistence of PrEP, providing us with a powerful new tool in our mission to end the HIV epidemic," said Dr. Carlos del Rio, Distinguished Professor of Medicine at Emory University School of Medicine's Division of Infectious Diseases and Co-Director of the Emory Center for AIDS Research. "The twice-yearly dosing regimen could significantly address key barriers faced by those using PrEP more frequently, particularly the daily oral PrEP users, such as adherence and stigma. We also know from research that many people who need or want PrEP tend to prefer less frequent dosing regimens."

FDA's Review of Gilead's Submission on Yeztugo^®The approval of the New Drug Application (NDA) is based on the data from Gilead's Phase 3 trials, PURPOSE 1 and PURPOSE 2.

The primary analysis data from the PURPOSE 1 trial (NCT04994509) conducted among cisgender women in sub-Saharan Africa show that Yeztugo^®None of the 2,134 subjects who received subcutaneous injections of Yeztugo® twice a year in the group became infected with HIV, Yeztugo^®Reduced the HIV infection rate by 100% and outperformed once-daily oral Truvada in preventing HIV infections.^®(Emtricitabine 200mg/Tenofovir Disoproxil Fumarate 300mg; F/TDF).

In the PURPOSE 2 trial (NCT04925752), conducted among a broad and geographically diverse population of cisgender men and gender-diverse individuals, Yeztugo is administered subcutaneously twice a year.^®In group 2179, there were two cases of HIV infection among the subjects, confirming Yeztugo.^®99.9% of the subjects in the group were not infected with HIV, and in terms of preventing HIV infection, Yeztugo^®Superior to once-daily oral Truvada®. In these two trials, compared with the background HIV incidence (bHIV), Yeztugo^®All demonstrated significantly superior HIV prevention efficacy and were generally well-tolerated, with no significant or new safety issues identified.

These two research data have been published in The New England Journal of Medicine. Based on the trial results and further considerations, the December 2024 issue of Science magazine selected Lenapev as the 2024 Scientific Breakthrough of the Year.

Yeztugo^®Received FDA approval under priority review. Additionally, in October 2024, Yeztugo® received Breakthrough Therapy Designation, which aims to expedite the development and review of new drugs that may offer significant improvements over existing therapies.

To date, HIV remains a major global public health issue. Since AIDS was first identified as a new disease in 1981, more than 80 million people worldwide have been infected, and over 40 million have died from the disease. According to data from the Chinese Center for Disease Control and Prevention, by the end of 2022, there were 1.223 million reported HIV/AIDS cases still living in China, with a cumulative total of 418,000 reported deaths.

Outside the United States, Gilead is implementing an access strategy under the guidance of global health advocates and organizations, prioritizing speed and providing the most efficient pathway for the registration, approval, and access of lenacapavir, administered twice a year, for pre-exposure prophylaxis (PrEP).

Gilead Sciences has submitted a Marketing Authorization Application (MAA) and an EU-M4all application to the European Medicines Agency (EMA), both of which have been validated by the EMA and will be reviewed under an accelerated assessment timeline. Gilead has also submitted registration applications for lenacapavir, administered twice yearly for PrEP, to regulatory authorities in Australia, Brazil, Canada, and South Africa. Additionally, following the FDA approval of Yeztugo®, Gilead is preparing to submit additional applications in countries that rely on FDA approval for registration, including Argentina, Mexico, and Peru. Gilead will continue to provide updates on other registration submissions.