The news comes just three weeks after Merck paused its Phase II IMAGINE-DR trial, which was studying a combination of islatravir with MK-8507.
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Late Monday afternoon, word hit the wires that Merck was pausing enrolment in two Phase III trials of islatravir (MK-8591), an investigational oral drug intended for pre-exposure prophylaxis (PrEP) in people at increased risk of the human immunodeficiency virus (HIV).
The news comes just three weeks after Merck paused its Phase II IMAGINE-DR trial, which was studying a combination of islatravir with MK-8507, a non-nucleoside reverse transcriptase inhibitor. This followed findings by an External Data Monitoring Committee (eDMC) that the combination was related to decreases in total lymphocyte and CD4+ T-cell counts.
One week after that, Merck and Gilead announced they were pausing a Phase II trial of islatravir and lenacapavir in HIV. The partners said the pause was implemented “out of an abundance of caution” to allow them time to consider potential protocol adjustments in light of Merck’s first announcement.
Islatravir is an inhibitor of nucleoside reverse transcriptase translocation designed to be administered once every month. Merck said that participants currently enrolled in the trial will continue to be given the study drug. The IMPOWER 24 study is assessing the efficacy and safety of islatravir compared to once-daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as a PrEP for cisgender men and transgender women at high risk of developing HIV.
The company said the enrollment pause would enable it to conduct further analyses of the two Phase III trials, along with other ongoing studies. Based on the recommendation of the islatravir eDMC, Merck will implement additional monitoring measures, including more frequent assessments of total lymphocyte and CD4+ T-cell counts.
“We continue to apply learnings from our HIV program as we move forward with the development of islatravir in both treatment and PrEP,” Dr. Joan Butterton, vice president, infectious diseases, global clinical development at Merck Research Laboratories said in a statement. “Merck remains committed to developing tools to help address unmet needs in HIV treatment and prevention to contribute to the global effort against the ongoing HIV epidemic.”
Merck’s initial findings indicated that total lymphocyte and CD4+ T-cell counts were decreased in participants across various company-sponsored trials of islatravir at varying dose levels. The company noted a dose-dependent decrease in lymphocyte counts in a Phase II study of patients at low risk of HIV-1 infection, though this did not lead to clinical adverse events. In another two Phase III trials studying an ISL in HIV-1 virologically suppressed patients, a small treatment-related mean decrease in CD4+ T-cell counts was noted.
“All clinical studies provide important learnings to help us in the fight against HIV, and we are grateful to the patients and investigator for their contributions,” Butterton said at the time of the Merck/Gilead trial pause.
