Merck pauses 2 more trials of backbone HIV drug over red flag, raising doubts about multipronged R&D strategy

Are the foundations of Merck’s broad HIV development program crumbling? Having already paused combination work in response to a red flag, Merck has now temporarily stopped enrollment in phase 3 studies that are testing the backbone of its HIV strategy as a monotherapy.

News of trouble at Merck emerged last month when the company paused development of an asset, MK-8507, that was central to its plans to create an oral, once-weekly treatment for HIV patients. The action followed the discovery of falls in total lymphocyte and CD4+ T-cell counts in patients who took MK-8507 in combination with backbone therapy islatravir.

At the time, Merck fingered MK-8507 as the problem and expressed confidence in the overall profile of islatravir, despite analyses of other studies showing it may affect white blood cell counts to some extent. Days later, Gilead Sciences and Merck paused a trial that was testing islatravir with lenacapavir.

The fallout has now spread to two phase 3 clinical trials that are giving islatravir orally once a month for preexposure prophylaxis (PrEP) of HIV infection. Merck saw dose-dependent falls in lymphocyte counts when it reviewed data from an ongoing phase 2 trial of monthly islatravir for PrEP in response to the red flag in the MK-8507 study, but, with the mean decreases falling in the normal range and no signs of increased clinical adverse events, forged ahead in the indication.   

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Less than three weeks later, Merck has changed its plans. At the recommendation of the external data monitoring committee, the Big Pharma company is pausing enrollment but continuing to dose existing participants. Merck is using the pause to implement extra monitoring measures for study participants, notably increased total lymphocyte and CD4+ T-cell assessments.  

The increased frequency of assessments points to a potential problem for Merck even if it can work through the current setbacks and get islatravir to market. If regulators make routine cell monitoring of islatravir patients a condition of approval, they could kill off the chances of the drug becoming a significant commercial product for Merck.

While Merck’s HIV program could weather the loss of MK-8507, islatravir is integral to the strategy. Merck has called islatravir the foundation of its broad HIV development program, reflecting its plans to use the molecule in its own once-daily and once-weekly oral treatments, its once-monthly and once-yearly PrEP products, and the Gilead-partnered long-acting oral and injectable treatments.