FDA sets early February 2027 to decide on a new PrEP option between daily pills and long-acting injections
The U.S. Food and Drug Administration (FDA) has accepted Gilead Sciences’ supplemental New Drug Application (sNDA) for a once-weekly oral version of the drugmaker’s Yeztugo for HIV prevention (PrEP), setting a target action date of February 2, 2027. If approved, the pill would offer a “middle option” between daily oral PrEP and long-acting injections.
“This represents the first of what we hope will be many long-acting oral HIV prevention options and further expands the PrEP toolbox,” said Aniruddha Hazra, MD, associate professor of medicine at the University of Chicago and a physician at Howard Brown Health. “While much of the recent conversation around next-generation PrEP has focused on long-acting injectables, injections are not the ideal fit for everyone. Offering non-injectable long-acting options is a patient-centered approach that allows individuals to choose a prevention strategy that best aligns with their preferences and needs.”
Marketed for PrEP under the brand name Yeztugo, lenacapavir is Gilead’s game-changing anti-HIV drug. Lenacapavir was approved as a long-acting injectable for PrEP by the FDA in June 2025 as a pair of shots administered every six months. (In December 2022, the FDA approved the same long-acting injectable formulation of lenacapavir as Sunlenca, a component of HIV treatment for people on complex regimens who had few options.)
The weekly PrEP pill is expected to keep the Yeztugo brand name, a Gilead spokesperson told POSITIVELY AWARE.
Results from Gilead’s PURPOSE 1 and PURPOSE 2 clinical trials demonstrated lenacapavir was highly effective at preventing HIV high efficacy for lenacapavir-based PrEP among cisgender women, cisgender men and gender-diverse people.
Dr. Hazra outlined for POSITIVELY AWARE some of the benefits of a weekly PrEP pill—for both patients and providers—over current long-acting injectables.
“From an implementation perspective, long-acting oral PrEP may also help address some of the logistical challenges associated with injectable PrEP,” he said. “Current long-acting injectable agents require specialized infrastructure, medication procurement pathways and recurring clinic visits, which can be difficult to sustain in lower-resourced settings. Weekly oral options could preserve many of the benefits of long-acting prevention while simplifying delivery.”
Lenacapavir tablets are already approved as an initial loading dose when starting long-acting injectable Yeztugo (or for Sunlenca) and as a bridging dose, in case a person misses their next injection appointment by more than two weeks. Current prescribing guidelines call for taking one 300 mg lenacapavir tablet once every seven days until the next set of injections. The oral bridge can be maintained for up to six months. The weekly pill under review by the FDA is also a 300 mg dose of lenacapavir.
Dosing will ultimately be determined by the FDA, the Gilead spokesperson said. Similar to long-acting injectable Yeztugo, the drugmaker expects there will be a loading stage for the weekly pill. The current Yeztugo tablets approved for injectable Yeztugo can be taken with or without food.
For now, Gilead is focused on getting the weekly Yeztugo pill approved in the U.S., according to the spokesperson, who said requirements for approval in other parts of the world or by other regulatory agencies may vary. “Gilead continues to evaluate the appropriate path forward in other regions,” the spokesperson said.
A once-yearly injectable version of Yeztugo is currently being tested in a phase 3 trial called PURPOSE 365. Merck & Co. is working on a once-monthly pill for PrEP, known as MK-8527, which is also in phase 3 trials.
As longer-acting oral medications for HIV prevention and treatment are being developed, adherence to these new regimens could become even more important so that the virus does not develop resistance. Drugmakers are thinking about how people on PrEP or on HIV treatment will handle new, longer dosing schedules. Dr. Hazra believes people are already starting to adapt.
“Weekly dosing has already become normalized across many other therapeutic areas, particularly with GLP-1 agonists, and may not be as challenging for patients to adopt as some assume,” he said. “For many individuals, taking a medication once weekly may represent a meaningful reduction in dosing burden while avoiding injections altogether.
“Ultimately, expanding the menu of long-acting options will help ensure that PrEP delivery is both patient-centered and scalable across a wide range of clinical settings.”