With Positive Phase 2 Results for Monthly Oral PrEP, Merck Plans Two, Phase 3 Trialls | IAS 2025

An oral version of HIV preexposure prophylaxis (PrEP) that can be taken monthly instead of daily showed good safety and pharmacokinetic characteristics that backed up the monthly dosing, according to results presented today at the International AIDS Society meeting in Kigali, Rwanda. Merck, the maker of the drug provisionally named MK-8527, announced earlier this week that it will sponsor two phase 3 trials of MK-8527, one among adolescent girls and young women in Kenya, South Africa and Uganda, and the other in 16 countries throughout the world. They are called EXPrESSIVE-10 and EXPrESSIVE-11, respectively.

According to information posted on clinicaltrials.gov, EXPrESSIVE-11 will compare an 11-milligram dose of MK-8527 with Truvada (emtricitabine/tenofovir disoproxil fumarate), Merck’s daily oral version of PrEP. Information on EXPrESSIVE-10 hasn’t been posted yet on clinicaltrials.gov, a central repository of information about clinical trials maintained by the National Library of Medicine.

On the right: Kenneth Mayer, M.D., presents phase 2 results for MK-8527, an oral version of HIV PrEP that has a once-a-month dosing schedule.

The phase 2 results reported today by Kenneth Mayer, M.D., a Harvard Medical School professor, showed a high prevalence of adverse events, with about two-thirds of the patients treated with MK-8527 experiencing an adverse event but most were mild and that proportion matched the proportion affected by adverse events in the placebo group. There was just one serious adverse event that the researchers considered related to the drug. A woman had a spontaneous abortion of a fetus at six weeks gestation. Mayer said the individual had a history of abortions and complications. The data Mayer presented showed two people discontinued the study because of severe adverse effects, one because of a drop in CD4/lymphocyte count and the other because of hypoesthesia (numbness). Overall, the most common drug-related adverse events were headache, nausea and drops in CD4/lymphocyte counts, but Mayer noted that the percentage of people affected was similar in the placebo.

The pharmacokinetics showed proportionality — the higher the dose of the MK8527, the higher the concentration in the blood, said Mayer. The pharmacokinetics also indicate that levels stay high enough to fend off an HIV infection over the course of a month, according to data shown by Mayer.

Oral PrEP has been overshadowed recently by the long-acting injectable versions of the preventive antiviral, Gilead Science’s lenacapavir, which theFDA approved last month and ViiV Healthcare’s cabotegravir long-acting, which was approved by the FDA in late 2021. But Mayer remarked that “some people don’t want to take shots” and that although oral PrEP with a daily dosing schedule is protective against HIV infection, the everydayness results in adherence shortcomings. The new World Health Organization recommendations for HIV prevention and care issued on Monday do not favor one form of PrEP or another, and WHO officials have stressed the importance of choice, pointing to research that suggests that when people have options, they are more likely to use PrEP.

Research into an HIV vaccine has failed to yield one so far, so HIV researchers and healthcare officials have pinned hope on PrEP as a way to reduce the number of new infections. After falling steadily for years, the number of new infections worldwide has plateaued recently.

The phase 2 trial that Mayer reported assessed three different doses of MK-8527 — 3 mg, 6 mg and 12 mg. The researchers enrolled about 100 people for each of those doses and then another 50 for a placebo group. All the study participants were adults who had a low likelihood of exposure to HIV. The study was conducted in the U.S., South Africa and Israel, with the greatest number of participants coming from the United States. They took the experimental monthly pill for six months.