FDA removes clinical hold on Bellicum's cell therapy
- Bellicum Pharmaceuticals, Inc. announced April 11 that the Food and Drug Administration removed the clinical hold on its BPX-501 trials of its engineered cell therapy. The program had been halted in January 2018 due to three cases of encephalopathy, one of which resulted in a patient death.
- The FDA removed the hold following Bellicum's addition of guidelines for comprehensive monitoring and management of neurologic adverse events associated with hematopoietic stem cell transplantation.
- With the hold lifted, Bellicum is cleared to initiate clinical trials in adult acute myeloid leukemia (AML) and in pediatric patients with either AML or primary immunodeficiencies (PIDs). News of the removal prompted a jump in Bellicum's stock of about 20% Thursday over Wednesday's closing price.
Bellicum previously 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.
That approach was reconsidered briefly after the appearance of the three cases of brain injury, thought to be linked to administration of Bellicum's drug.
It was difficult to assess whether the brain injury occurred as a direct result of treatment with BPX-501, as certain patients receiving stem cell transplants are already at some risk of encephalopathy. Plus, there were some pre-existing conditions among the three patients who experienced brain injury that may have exacerbated their immune responses, Bellicum investigators hypothesized.
"Given the number of confounding factors in patients in the BPX-501 study, including the unknown etiology of the encephalopathies and the administration of treatments such as corticosteroids and anti-virals, the cause and timing of encephalopathies are not understood,” company spokesperson Brad Miles wrote in an email to BioPharma Dive.
Nonetheless, after speaking to regulators and tweaking study protocols, including the revision of its investigator brochure and patient informed consent documents, Bellicum got an OK from the FDA to resume investigation of BPX-501.
The addition of BPX-501 T cells is thought to boost immune recovery following stem cell transplantation in pediatric patients with PIDs. This anti-leukemic function comes from the engineered T cells themselves, and essentially replaces the T cells that were depleted as a result of allogeneic HSCT transplant. But if those same cells procured from a healthy donor trigger graft-versus-host disease, the hope is that those cells can be eliminated quickly.
Jefferies analysts said a lift of the hold was expected, adding that the number of reports of encephalopathy across the database of candidates receiving BPX-501 compared "favorably with a background encephalopathy incidence rate of 5-20% in allo-transplant."
Jefferies suggested comparisons with CAR-T don't hold up, citing talks with key opinion leaders who note that the two types of immune reaction were dissimilar — the reactions in patients in the Bellicum trial did not occur immediately, but instead, 40-210 days post-transplant.
Jefferies added that interim data on BPX-501 from the company's BP-004 study in Europe — trials which were not affected by the FDA's hold — were promising.
- Bellicum Pharmaceuticals, Inc. Statement
- BioPharma Dive Bellicum outlines path to restart US studies of cell therapy