- Merck & Co. disclosed Monday afternoon that it is pausing enrollment in two studies of its checkpoint inhibitor Keytruda (pembrolizumab) due to patient deaths.
- KEYNOTE-183 and KEYNOTE-185 will not recruit any further patients based on a recommendation from an external data monitoring committee.
- The two multiple myeloma studies are testing Keytruda in combination and Merck is pausing the studies "to better understand more reports of death in the Keytruda groups." Merck did not give further details.
The two studies that Merck is currently pausing are testing Keytruda in combination with Pomalyst (pomalidomide) with low-dose dexamethasone and Revlimid (lenalidomide) with low-dose dexamethasone, respectively, against those combinations alone.
According to the Merck statement, which gave little clarification, the reports of death were only in the combination arms that included the PD-1 inhibitor.
Bristol-Myers Squibb and AstraZeneca are testing their respective checkpoint inhibitors in multiple myeloma trials as well. Neither have reported similar patient deaths, although Evercore ISI analyst Umer Raffat notes the studies began about six months later than Merck's trials.
Previous studies of Keytruda in this patient population gave no indication of increased safety signals.
While Bristol-Myers' Opdivo (nivolumab) maintains an edge in sales, Keytruda is rapidly becoming the market-leader in this space since Opdivo failed in a lung cancer trial last summer. With first-line approvals in hand, Keytruda is expected to eventually overtake Opdivo due to the size of the lung cancer market.
This new development in the PD-1/L1 space highlights that there may be more differences amongst the class than previously thought. A recent failure by Roche’s Tecentriq (atezolizumab) in bladder cancer helped catalyze speculation that all checkpoint inhibitors are not made the same.
Differentiation in the crowded class could result in a more divided market, with certain drugs used more in specific cancer types rather than a winner-takes-all market dynamic.
For Merck, Keytruda is its crown jewel. If these issues turn out to be part of a larger problem with the drug, it could be a major issue for Merck in the long run.