The FDA has placed a clinical hold on studies of Bellicum Pharmaceuticals’ lead candidate BPX-501 after three patients were reported to have developed encephalopathy—cases that the company acknowledged were deemed as related to the T-cell therapy being developed for blood cancers and inherited blood disorders.

The three patients are among more than 240 who have been treated with BPX-501 cells on three allogeneic haploidentical stem cell transplantation protocols, the company said.

“These three cases are complex, with a number of potential confounding factors—including, in certain of the cases, prior failed transplants, prior history of immunodeficiency, concurrent infection, and administration of rimiducid in combination with other medications,” Bellicum said in a statement. “Bellicum is awaiting formal communications from the FDA to determine the requirements for resuming studies, and will be working closely with the FDA to address their questions.”

Bellicum added that it is working with the FDA to assess the risk of encephalopathy in patients receiving BPX-501. The company’s statement noted that encephalopathy has been reported in previous studies detailing allogeneic stem cell transplant—and cited several risk factors for encephalitis/encephalopathy after allogeneic stem cell transplants, including prolonged immunodeficiency, selected medications, infections, and inflammatory processes such as graft-versus-host disease (GvHD).

BPX-501 is an adjunct T-cell therapy administered after allogeneic hematopoietic stem cell transplants (HSCT), and consists of genetically modified donor T cells that incorporate Bellicum’s CaspaCIDe® safety switch. The therapy designed to eliminate alloreactive BPX-501 T cells via administration of activator agent rimiducid should uncontrollable GvHD occur.