- After placing several Merck & Co. trials on clinical hold following a patient death, the Food and Drug Administration is following up with clinical holds for several other trials by competitors.
- AstraZeneca plc and Celgene Corp. announced Thursday morning that one trial is being placed on full clinical hold and five others on partial clinical hold. The trials are testing AstraZeneca’s PD-L1 inhibitor Imfinzi with Celgene immunomodulatory agents.
- Bristol-Myers Squibb Co. also announced that three clinical trials testing its PD-1 inhibitor Opdivo in combination were also put on partial clinical hold.
While no unexpected safety signals have been seen in any trials hosted by either AstraZeneca and Celgene or Bristol-Myers, the FDA is playing it safe.
The trials put on partial clinical hold will stop enrollment, yet allow those patients that have shown benefit to continue treatment. Meanwhile, patients in the trials put on full clinical hold will discontinue treatment completely.
These new clinical holds follow the reports from Merck earlier this summer that it was voluntarily pausing two studies — one testing Keytruda (pembrolizumab) in combination with Pomalyst (pomalidomide) and the other testing the PD-1 inhibitor with Revlimid (lenalidomide) — in multiple myeloma (MM) patients after reports of patient deaths.
The FDA promptly followed up with full clinical holds for three Keytruda studies in MM. In a rare move almost two months later, the FDA put out a statement about this decision – clearly foreshadowing other clinical holds to come.
While patient safety is paramount, this does raise business concerns for a number of companies. The PD-1/L1 inhibitors have been a closely watched class of drugs that have been touted as an amazing achievement in the treatment of cancer.
The strong efficacy of these drugs prompted the FDA to approve Keytruda and Opdivo (nivolumab) in a number of indications at a rapid clip. While only being on the market for a short time, the drugs have become instant blockbusters and are also some of the first oncology drugs to ever be features in direct-to-consumer advertisements.
The drugs have not only symbolized new innovation for the industry, but have served as triggers to revitalize two big pharmas that were in great need of some good fortune.
These safety concerns raise new questions about the class and could stall innovation in immuno-oncology if they are found to be widespread.
The trials on hold
The Celgene FUSION trials that were placed on partial clinical hold include the Phase 1b trial MEDI4736-MM-001 of Imfinzi and pomalidomide in MM; the Phase 2 trial MEDI4736-MM-003 of Imfinzi and daratumumab also in MM; the Phase 1/2 trial MEDI4736-NHL-001 of Imfinzi with chemotherapy in lymphoma and leukemia patients; the Phase 2 MEDI4736-MM-005 of Imfinzi with daratumumab in MM; and the Phase 2 MEDI4736-DLBCL-001 of Imfinzi with chemoptherpy or lenalidomide in patients with diffuse large B-cell lymphoma.
The FUSION trial placed on full clinical hold, MEDI4736-MM-002, was a Phase 1b study testing Imfinzi with lenalidomide in newly diagnosed MM.
The Bristol-Myers studies that were put on partial clinical hold include CheckMate-602, a Phase 3 study testing Opdivo with elotuzumab, pomalidomide and Dexamethasone in MM; CheckMate-039, a Phase 1 study of Opdivo and daratumumab in MM; and CA204142, a Phase 2 study of elotuzumab with pomalidomide and low-dose dexamethasone in combination with Opdivo.