- The Food and Drug Administration has placed three combination trials of Merck's flagship immunotherapy Keytruda (pembrolizumab) on clinical hold after a review of the studies found more deaths had occurred in the treatment arms.
- Merck had previously paused enrollment in two of the trials after initial reports of patient deaths. The three studies now on hold are testing Keytruda in combination with Celgene's Revlimid (lenalidomide) or Pomalyst (pomalidomide) plus dexamethasone in multiple myeloma.
- The clinical holds dent the positive momentum behind Keytruda, which secured several significant regulatory approvals in recent quarters. Yet, it is not clear whether the deaths observed in the studies represent a broader safety concern for the drug. All other studies with Keytruda remain ongoing, Merck said.
In light of the observed deaths, the FDA judged the risk to Keytruda treatment combined with Revlimid or Pomalyst to "outweigh any potential benefit for patients with multiple myeloma," Merck said in a July 5 statement.
Two of the three studies, KEYNOTE-183 and KEYNOTE-185, were placed on full clinical hold while the third, KEYNOTE-023, was placed on a partial clinical hold. All patients in the three studies will discontinue treatment with Keytruda.
The initial pause in enrollment and subsequent clinical holds come as a surprise as no treatment-related deaths had so far been reported in trial results from Keynote-023 or a Phase 2 study of Keytruda plus Pomalyst and dexamethasone.
Shares in the pharma slid more than 1% in Thursday morning trading.
All but one approval for Keytruda have been for solid tumors such as lung cancer, melanoma or bladder cancer. In March, however, Keytruda did secure its first indication to treat a blood cancer, receiving approval for classical Hodgkin lymphoma.
Multiple myeloma, a cancer of blood plasma cells in the bone marrow, is the second most common blood cancer. Celgene's Revlimid and Pomalyst are two standard treatments for the disease.
Two other studies are testing the two drugs paired with Bristol-Myers Squibb's Opdivo (nivolumab) and AstraZeneca's Imfinzi (durvalumab), Evercore ISI analyst Umer Raffat wrote in a July 5 note. No updates have disclosed similar treatment-related deaths, although both studies were initiated six to nine months after the Merck trials, Raffat said.