Merck announced an update regarding the Phase 2 IMAGINE-DR clinical trial (MK-8507-13), which is evaluating the investigational combination of MK-8507, a non-nucleoside reverse transcriptase inhibitor, and islatravir (ISL), a nucleoside reverse transcriptase translocation inhibitor, as a once-weekly oral treatment for HIV-1 infection. MK-8507 and islatravir, alone and in combination, are investigational and not approved for use.

Decreases in total lymphocyte and CD4+ T-cell counts were observed in study participants randomized to receive ISL+MK-8507. A review by the external Data Monitoring Committee (eDMC) determined that this effect was related to treatment with the combination of ISL+MK-8507; the greatest decreases were seen in the arms of the study receiving the highest doses of MK-8507 (200 mg and 400 mg). At the recommendation of the eDMC, Merck is stopping dosing in the trial, with continued monitoring of study participants. The company has notified investigators and paused development of MK-8507. Merck remains confident in islatravir’s overall profile and is continuing with development of islatravir across a range of settings including in treatment of patients living with HIV and in pre-exposure prophylaxis (PrEP). None of these other programs combine islatravir with MK-8507.

“Merck remains resolute in its commitment to help address the unmet needs of people living with HIV and continue to do our part in the global efforts to help end the HIV pandemic, which includes the ongoing development of islatravir,” said Dr. Joan Butterton, vice president, infectious diseases, Global Clinical Development, Merck Research Laboratories. “All clinical studies provide important learnings to help us in the fight against HIV, and we are grateful to the patients and investigators for their contributions.”

In light of the findings from the MK-8507-013 study, Merck conducted a review of trends in total lymphocyte and CD4+ T-cell counts in company-sponsored clinical trials of ISL across all indications and dosing regimens. A dose-dependent decrease in lymphocyte counts was observed in an ongoing Phase 2 trial (MK-8591-016), which is evaluating monthly ISL (60 mg and 120 mg) for PrEP in participants at low-risk of HIV-1 infection. In this population of HIV-1 uninfected participants, the mean decreases were in the normal range and there was no increase in clinical adverse events (AEs) related to infection. In addition, a small, treatment related mean decrease in CD4+ T-cell counts was observed through Week 48 in two Phase 3 trials, ILLUMINATE SWITCH A and ILLUMINATE SWITCH B (MK-8591A-017 and MK-8591A-018), which are evaluating doravirine 100 mg in combination with ISL 0.75 mg daily (DOR/ISL) in HIV-1 virologically suppressed participants. There was no increased incidence of AEs related to infections in participants receiving DOR/ISL relative to comparators through Week 48. Investigators for these trials have been informed and the trials are continuing. Full results from ILLUMINATE SWITCH A and ILLUMINATE SWITCH B will be presented at an upcoming medical meeting.