Newly published data is adding support behind Merck’s investigational pre-exposure prophylaxis drug, MK-8527.
The drug is a nucleoside reverse transcriptase translocation inhibitor, a new class of HIV drugs currently under investigation. The drugmaker also is researching the other novel drug in this class, islatravir, which is undergoing trials for HIV treatment both by itself and in fixed-dose combinations—one with doravirine and another with lenacapavir (Sunlenca [for treatment], Gilead).
As for MK-8527, investigators are studying the drug for HIV PrEP, noting that newly published preclinical data show the drug has potent antiretroviral activity and favorable pharmacokinetics that make it an “attractive clinical candidate,” according to lead author Izzat T. Raheem, PhD, a distinguished scientist in Discovery Chemistry at Merck Research Laboratories, and his co-authors (PLoS Biol 2025;23[8]:e3003308).
How Does MK-8527 Work?
MK-8527 is a PrEP candidate because it interferes with HIV viral replication, helping to prevent HIV acquisition. “Specifically, MK-8527 inhibits HIV reverse transcriptase through multiple mechanisms of action, including inhibition of translocation and delayed chain termination,” Dr. Raheem told Infectious Disease Special Edition. “Its pharmacokinetic profile supports sustained drug levels that can be maintained for a month after a single dose, representing a potential innovation over current daily oral PrEP options.”
What Clinical Research Is Behind MK-8527?
Two large phase 3 studies are under way. EXPrESSIVE-11 (MK-8527-011,NCT07044297) and EXPrESSIVE-10 (MK-8527-010, NCT07071623) will involve around 9,000 people worldwide, according to Dr. Raheem’s co-author Tracy L. Diamond, PhD, a senior principal scientist at Merck Research Laboratories. “The EXPrESSIVE-11 study will evaluate the safety and efficacy of MK-8527 among people with greater likelihood of HIV exposure in 16 countries; this study is already enrolling. In collaboration with the Gates Foundation, the EXPrESSIVE-10 study will evaluate the safety and efficacy of MK-8527 in young women and adolescent girls in sub-Saharan Africa and will begin enrolling soon,” Dr. Diamond told IDSE.
At IAS 2025, in Kigali, Rwanda, researchers presented phase 2 data that demonstrated safety and tolerability of the drug in a population at low risk of acquiring HIV. “In this study, the rates of adverse events were similar among those in the MK-8527 arms and those in the placebo arm, and no clinically meaningful changes were seen in laboratory tests, including total lymphocyte and CD4 T-cell counts,” Dr. Diamond said.
Oral versus Injectable
Current HIV PrEP options include daily oral pills or two options for long-acting injectables, cabotegravir (Apretude, ViiV Healthcare) or lenacapavir (Yeztugo [for PrEP], Gilead). MK-8527 could offer a once-monthly pill as an option for PrEP. “An oral prevention option like MK-8527 could represent a paradigm shift,” Dr. Raheem said. “We envision that monthly oral dosing could transform PrEP delivery and implementation models … [and could] help address real-world challenges such as adherence and stigma.
“A once-monthly oral PrEP option, such as MK-8527, could play a role in global efforts to reduce HIV incidence by addressing some of the persistent HIV prevention implementation challenges like access to healthcare and the stigma associated with daily HIV pills. We hope that MK-8527 could provide a user-friendly, healthcare system-friendly prevention option with the potential to be available in a variety of settings that allow for more flexibility and privacy.”
Drs. Diamond and Raheem are employees of MK-8527’s drugmaker Merck and own company stock.
By Meaghan Lee Callaghan
Source : Infectious Disease Special Edition
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