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.

European Trial Unaffected

BPX-501 is the subject of four Phase I/II trials in the U.S. and Europe:

  • BP-001 and BP-005, in adults with hematological cancers in which BPX-501 is administered after initial allogeneic HSCT;
  • BP-003, a single-site study in children with orphan inherited blood disorders in which BPX-501 is administered after initial allogeneic HSCT;
  • BP-004, in children with hematological cancers or orphan inherited blood disorders in which BPX-501 is administered after initial allogeneic HSCT;
  • BP-008, to treat post-transplant relapse in adults and children with blood cancers and evaluate the potential for a titrated dose of rimiducid to resolve uncontrolled GvHD while preserving BPX-501 cells

The BP-004 trial is not affected by the clinical hold since part of the study is occurring in Europe, where BPX-501 has been granted orphan drug designations for treatment in HSCT, and for activator agent rimiducid for the treatment of GvHD.

On December 9 at the 59th Annual Meeting of the American Society of Hematology (ASH), held in Atlanta, Bellicum presented positive results from BP-004, saying that donor BPX-501 cells infused after transplant expanded in vivo and persisted over time, contributing to improved immune recovery for patients in the study as compared to historical controls from the same transplant center.

BPX-501 and rimiducid also have orphan drug status from the FDA as a combination replacement T-cell therapy for the treatment of immunodeficiency and GvHD after allogeneic hematopoietic stem cell transplant.

Investors responded to the clinical hold announcement with a stock selloff that sent shares tumbling about 33% or $2.68 as of 10:23 a.m., to $5.51 per share.

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