The FDA has placed a clinical hold on Bellicum’s lead cell therapy. Bellicum suffered the setback after the FDA learned of three cases of brain damage possibly related to adjunct T-cell therapy BPX-501.
Houston, Texas-based Bellicum is developing BPX-501 to improve outcomes in patients who undergo partial-match hematopoietic stem cell transplants to treat hematological cancers and inherited blood disorders. The T-cell therapy is designed to fight infection, aid engraftment, stop disease relapse and, if needed, kill the rogue cells that trigger graft versus host disease.
Now, three cases of encephalopathy have brought the U.S. clinical development program to a halt.
Bellicum provided few details of the patients in its statement, saying only that they are complex cases with potentially confounding factors. But analysts at Jefferies published a note providing a fuller picture of the patients and the circumstances that led to the identification of the encephalopathy cases.
“One patient had a complex history with a prior history of primary immunodeficiency and had two concurrent viral infections. This patient ultimately died from encephalopathy which was confirmed through a brain biopsy. Two of the three patients had prior transplants. Also, two patients’ symptoms resolved. The cases initially were not characterized as treatment-related adverse events but after the one fatality both cases were reviewed and reclassified as treatment related,” the analysts wrote.
Bellicum is now waiting to receive a formal notice from the FDA that will guide the steps it takes to get the program back on track. Analysts at Jefferies think Bellicum can resolve the hold within three months. Enrollment in a European clinical trial is continuing in the meantime. Bellicum is aiming to file for approval in Europe next year, although that plan could be derailed if the EMA’s response to the encephalopathy cases hardens and stops enrollment.
At this stage it is unclear why three cases of encephalopathy potentially linked to BPX-501 have emerged out of the blue—the cell therapy was previously used in 240 patients, after all. Hematopoietic stem cell transplants are associated with encephalopathy—one study puts the rate of the side effect at 6%—but the BPX-501 program had been free of the adverse event until now.
News of the clinical hold wiped 38% off Bellicum’s stock price in after-hours trading. That drop adds to the already-steep decline in the value of the biotech since the highs of early 2015. And it diminishes the company's ability to pull off the fundraising necessitated by its declining bank balance.