FDA Approves Gilead’s Twice-Yearly Injectable Lenacapavir (Yeztugo) for HIV Prevention
Gilead’s yeztugo, a long-acting HIV capsid inhibitor shows 96–100% efficacy in phase 3 trials and aims to expand access worldwide through regulatory filings and support programs.
Gilead Sciences, Inc announced today that the US Food and Drug Administration (FDA) has granted approval for yeztugo, the company’s first-in-class, long-acting HIV-1 capsid inhibitor, for use as a twice-yearly pre-exposure prophylaxis (PrEP) to prevent HIV infection. This approval marks the introduction of the first and only biannual injectable option for HIV prevention, representing a significant milestone in expanding and personalizing HIV prevention strategies.1
Yeztugo’s approval is supported by compelling clinical data from Gilead’s phase 3 PURPOSE 1 and PURPOSE 2 trials, and comes as a major advance in overcoming long-standing challenges with daily oral PrEP adherence. To provide expert perspective on the impact and future of this therapy, Jared Baeten, MD, PhD, senior vice president of clinical development and virology at Gilead, shared insights on what this new option means for people at risk of HIV, and how it fits into the broader prevention landscape.
Clinical trial data highlight lenacapavir’s remarkable efficacy. PURPOSE 1 enrolled 2,134 sexually active, HIV-negative cisgender women in South Africa and Uganda, with zero HIV infections observed, equating to a 100% risk reduction compared to the background incidence rate of 2.41 per 100 person-years (95% CI, 1.82–3.19). By contrast, oral daily regimens like emtricitabine/tenofovir alafenamide (F/TAF) and emtricitabine/tenofovir disoproxil fumarate (F/TDF) showed incidences of 2.02 and 1.69 per 100 person-years, respectively.2
PURPOSE 2, which enrolled a geographically diverse group of cisgender men and gender-diverse participants, reported only two HIV infections among those receiving yeztugo. This translated to a 96% risk reduction, with 99.9% of participants remaining HIV-free during the trial period, confirming the drug’s superiority over background incidence rates.2
Discussing the potential of yeztugo to address adherence and stigma challenges, Baeten emphasized, “This medicine, lenacapavir, offers a new option for people who need or want HIV prevention, and it's a medicine that, for many people, could meet them where they are. It's an injection just twice a year that can be discrete, private, and allows people to overcome many of the challenges of adherence—particularly the adherence to a pill every day—as well as challenges of stigma or privacy that people face when they, for example, have to bring home a bottle of HIV PrEP pills.”
“We built, over now nearly two decades since this research started, a medicine that—because it's given as an injection just twice a year—could really try to meet people where they are. This offers a new opportunity for people to make an empowered choice for what they might want for HIV prevention.”
Yeztugo was previously approved in December 2022 under the brand name Sunlenca for the treatment of multidrug-resistant HIV, based on the CAPELLA trial showing efficacy in heavily treatment-experienced patients receiving twice-yearly subcutaneous injections.3 As a novel HIV-1 capsid inhibitor, lenacapavir blocks multiple essential viral lifecycle stages, representing a new class of antiretroviral therapy.
Regarding the drug’s availability, Baeten explained, “Our intent is, within a couple of days of approval, we'll be able to provide lenacapavir within the channels of ways that medicines are provided within pharmacy systems in the United States. We anticipate that individual insurance plans—75% of them—will incorporate it within the first six months, and 90% within a year. It's really important to remember for PrEP that PrEP has been covered by insurance plans in the United States, and for individuals without insurance, medication assistance programs exist. So people should really be talking to their doctors about the PrEP options and what might work for them.”
Gilead has also submitted applications to the European Medicines Agency (EMA), including through the EU-Medicines for All (EU-M4all) program aimed at accelerating access in low- and middle-income countries.
Baeten highlighted the extensive preparation Gilead has undertaken to support clinicians and health systems in adopting this biannual injection, “PURPOSE included two very large clinical trials—8,000 people in total—where 99.9% of those who received lenacapavir remained HIV-free. The program touched across five continents and was the largest and most diverse in terms of geography, age, gender, race, and ethnicity ever conducted for HIV prevention. Our teams have been working for over a year on educational tools and clinician engagement to help integrate this twice-yearly injection into existing health systems and counseling workflows.”
Looking ahead to ongoing real-world monitoring, Baeten remarked, “The work in this field does not end with FDA approval. We have planned several initiatives over the next few years to understand how lenacapavir is used in real-world settings and to ensure it meets diverse community needs. This includes continued data collection from the PURPOSE trials, funding 16 investigator-sponsored studies in the US, and conducting implementation science research globally.”
While yeztugo offers unprecedented convenience and efficacy, challenges remain in ensuring equitable global access and affordability. Gilead has pledged to pursue voluntary licensing agreements and equitable pricing strategies, particularly to benefit low-income countries. With its twice-yearly injectable dosing, lenacapavir represents a potentially transformative step in HIV prevention, removing key barriers and enabling more people at risk to protect themselves effectively.
