Yeztugo® (Lenacapavir) Becomes the First FDA-Approved 6-Month HIV Prevention Option

Gilead Sciences, Inc. has announced the approval of its new injectable HIV prevention drug, Yeztugo (lenacapavir), by the U.S. Food and Drug Administration (FDA). This landmark approval introduces the first and only twice-yearly injectable option available in the U.S. for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV. The drug is approved for use in both adults and adolescents weighing at least 35 kilograms. The approval is based on data from the Phase 3 PURPOSE 1 and PURPOSE 2 trials, which demonstrated that over 99.9% of participants remained HIV-negative while on Yeztugo.

This development marks a significant breakthrough in the fight against HIV, with Yeztugo offering a new and promising strategy to combat the epidemic. Gilead Sciences CEO Daniel O'Day highlighted the potential of Yeztugo to transform HIV prevention efforts, emphasizing its convenient twice-yearly administration and the promising clinical trial outcomes. The approval is seen as an opportunity to advance towards ending the HIV epidemic, a goal that Gilead has been working towards for decades.

Despite the availability of PrEP options since 2012, including an earlier medication developed by Gilead, uptake has been limited. According to the Centers for Disease Control and Prevention (CDC), only about 36% of eligible individuals in the U.S. were prescribed PrEP in 2022. Barriers such as adherence challenges, stigma, and low awareness have contributed to the low uptake, especially among certain communities, including women, Black/African American and Hispanic/Latino populations, and those in the Southern U.S.

Yeztugo is positioned to address some of these barriers by offering a less frequent dosing option, which could improve adherence and reduce stigma. Carlos del Rio, MD, from Emory University, noted that the twice-yearly injection could significantly impact PrEP uptake and persistence, providing a powerful new tool to end the HIV epidemic.

The FDA approval was supported by robust data from the PURPOSE 1 and PURPOSE 2 trials. In the PURPOSE 1 trial, no HIV infections were reported among the Yeztugo group of 2,134 participants, demonstrating its superiority over once-daily oral Truvada in preventing HIV infections among cisgender women in sub-Saharan Africa. The PURPOSE 2 trial showed similar success, with only two infections in the Yeztugo group out of 2,179 participants, confirming its effectiveness among a diverse population of cisgender men and gender-diverse individuals.

Yeztugo has received FDA approval under Priority Review and was granted Breakthrough Therapy Designation in October 2024, expediting its development and review due to its substantial improvement over existing therapies.

Gilead is committed to making Yeztugo accessible to a broad audience in the U.S., collaborating with insurers and healthcare providers to ensure coverage. The company has established programs to reduce out-of-pocket costs for insured individuals and provide the medication at no cost to eligible uninsured individuals.

Gilead is also pursuing regulatory approvals in other countries, with a focus on ensuring global access to Yeztugo. Applications for marketing authorizations have been submitted in regions including Europe, Australia, Brazil, Canada, and South Africa. The effort aims to enable swift regulatory review and approval, following the successful FDA approval.

Yeztugo represents a significant advancement in HIV prevention strategies and has the potential to become a cornerstone in the ongoing effort to reduce new HIV infections globally.