Combos, FDA

Troubled by deaths, FDA orders Merck to slam the brakes on three Keytruda studies

Roger Perlmutter, Merck

A month after Merck flagged a higher risk of death in two combo studies using its flagship drug Keytruda, the FDA has followed up with a clinical hold that will slam the brakes on further treatment in three multiple myeloma trials.

Merck said a few weeks ago that it planned to continue treatment in the two studies – KEYNOTE 183 and KEYNOTE 185 – while pausing enrollment of new patients. Those multiple myeloma trials matched Merck’s blockbuster therapy with two drugs from Celgene, Pomalyst and its big drug Revlimid.

The FDA, though, wants patients taken off of Keytruda in the two Phase III studies and also ordered Merck to stop treating patients in KEYNOTE-023 Cohort 1, matching Keytruda in combination with lenalidomide and dexamethasone in patients who received prior anti-multiple myeloma treatment with an immunomodulatory (IMiD) treatment (lenalidomide, pomalidomide or thalidomide).

The latest news compounds a new headache for Merck just as it was putting some serious distance between itself and Bristol-Myers Squibb’s troubled rival PD-1 drug Opdivo. The pharma giant notes that these are the only three trials – among dozens in the clinic – that are affected by the agency’s decision. Merck has never offered an explanation, or theory, about the higher risk of deaths in these combination studies.

Merck shares were down about 1% in after-market trading.

The clinical hold also raises questions about some of the other combination studies in the clinic. Evercore ISI’s Umer Raffat notes:

It will be very interesting to see the fate of BMY’s Checkmate-602 (nivo + pom/dex) as well as Celgene/AZN’s FUSIONMM-03 of durva+dara+pom/dex in multiple myeloma. Here’s what we know at present:  BMY trial was initiated ~6 months after MRK’s unsuccessful myeloma trials … and the Celgene/AZN trial was initiated ~9 months after MRK’s

“Patient safety is Merck’s primary concern, and we are grateful to the study investigators and patients involved in these studies for their commitment to this important research,” said Roger Perlmutter, president, Merck Research Laboratories. “Merck’s development program for KEYTRUDA, spanning more than 30 different tumor types, has one priority: helping patients suffering from cancer.”


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