Merck hits the brakes on development program as safety fears trigger alarm
In a surprise setback, Merck has slammed the brakes on the development of an experimental HIV drug — including a Phase II trial — after investigators flagged a drop in immune cell counts that an external committee determined was related to treatment.
The Phase II study that first sounded the alarm, dubbed IMAGINE-DR, was testing the once-weekly combination of MK-8507 (a non-nucleoside reverse transcriptase inhibitor) and islatravir, or ISL, a nucleoside reverse transcriptase translocation inhibitor.
Whereas Merck is pausing all programs involving MK-8507, the company says it “remains confident in islatravir’s overall profile” and will carry on with it.
For Mizuho analyst Mara Goldstein, that offers a glass half full situation.
“MRK’s lead anti-HIV candidate is islatravir (ISL), which we see as undisturbed at this point,” she wrote. “Based on a larger body of clinical data for ISL’s anti-HIV efficacy including the recent positive top-line update (see NOTE), we are not forecasting changes in the broader ISL-based HIV studies, and our model remains the same.”
Islatravir is also one of the two centerpieces of Merck and Gilead’s joint effort to develop a long-acting HIV therapy, alongside Gilead’s capsid inhibitor lenacapavir.
Joan Butterton, VP of infectious diseases global clinical development at Merck Research Laboratories, noted Merck remains “resolute” in its pledge to help end the HIV pandemic and highlighted that all clinical studies provide important “learnings.”
In IMAGINE-DR, study participants randomized to receive ISL+MK-8507 saw a decrease in total lymphocyte and CD4+ T cell counts. The greatest drops were observed in the arms of the study receiving the highest doses of MK-8507, namely 200 mg and 400 mg.
The external data monitoring committee concluded that the adverse effect had to do with the treatment and recommended stopping the trial. Merck obliged, and reviewed all of its trials involving ISL with a special eye to those metrics.
Here’s what they found:
- The ongoing Phase II trial (MK-8591-016) is evaluating monthly ISL for PrEP in participants with low risk of HIV-1 infection. Among this uninfected group, there was a dose-dependent decrease in lymphocyte counts but mean decreases were in the normal range, and there was no increase in clinical adverse events related to infection.
- ILLUMINATE SWITCH A and ILLUMINATE SWITCH B (MK-8591A-017 and MK-8591A-018) are two Phase III trials evaluating doravirine in combination with ISL daily (DOR/ISL) in HIV-1 virologically suppressed participants. Here, Merck found a small, treatment related mean decrease in CD4+ T cell counts through week 48, but no increased incidence of AEs related to infection.
Merck recently reported positive data from the ILLUMINATE studies, suggesting the DOR/ISL combo has comparable efficacy as existing antiretroviral therapies.
“Investigators for these trials have been informed and the trials are continuing,” the company wrote.