- Bellicum Pharmaceuticals Inc. appears nearer to resolving a clinical hold placed on trials of its lead T-cell therapy last month, outlining on Friday its intention to more thoroughly monitor neurotoxicity risks to patients as part of study revisions required by the Food and Drug Administration.
- Reports of three cases of encephalopathy, including one fatal, spurred the FDA in late January to suspend U.S. studies of the treatment, known as BPX-501 and designed for adjunctive use in patients following a stem cell transplant.
- Shares in the Houston-based biotech rose in early Friday trading, likely reflecting the relatively modest nature of the proposed changes to the study's protocol. Bellicum said it would submit a full response to the FDA's concerns within a few weeks.
Neurotoxicity-related safety concerns in clinical studies always prompt close scrutiny from regulators and investors alike. That's particularly true in cell therapy, where the (relatively) early nature of the field, as well as Juno Therapeutics Inc.'s experience with fatal brain swelling in a study of its since-discontinued CAR-T therapy, have led to more caution.
When first announcing the clinical hold from the FDA on BPX-501, Bellicum indicated the three cases of encephalopathy were judged to be "possibly related" to treatment. All three patients had what the company characterized as "confounding factors," such as prior failed transplants and prior history of immunodeficiency.
Bellicum will now add further monitoring and management of neurotoxicity to studies of BPX-501, revising both the documents provided to study investigators and patient informed consent forms to reflect the changes.
BPX-501 is administered following allogeneic hematopoietic stem cell transplants to improve the speed at which patients' immune systems reconstitute and boost graft-versus-leukemic effect in certain blood cancers.
Pediatric stem cell transplant recipients are already at some risk of encephalopathy, noted Jefferies analyst Biren Amin in a Jan. 31 note written after Bellicum's announcement of the hold.
Still, Bellicum has positioned BPX-501 as a less risky type of cell therapy due to its so-called "safety switch," which is designed to eliminate alloreactive BPX-501 T-cells in the event of uncontrolled graft-versus-host disease.
If Bellicum's reading of the FDA's requirements for restarting U.S. studies holds true, the company looks to be on track to resolve the suspension relatively quickly — in line with the one to three months predicted by Amin in his Jan. 31 note.
Bellicum had reported the encephalopathy cases to the European Medicines Agency, but the company's BP-004 registration study there was not affected.
Moving fast in cell therapy, however, has backfired disastrously before. For example, three patient deaths in 2016 led Juno and the FDA to halt a study of the Seattle biotech's JCAR015 candidate. The regulator quickly cleared dosing to resume after Juno modified the trial protocols, only for two more patients to subsequently die. Juno later shuttered clinical development of JCAR015.