FDA Puts Clinical Hold on BPX-501 After Patients Develop Encephalopathy

The FDA put a clinical hold on the investigational cellular immunotherapy BPX-501, halting four U.S. studies assessing the drug’s use for cancer and orphan-inherited blood disorders. The agency placed the hold after three patients developed encephalopathy that was deemed possibly related to treatment. BPX-501 is an adjunct T-cell therapy administered after allogeneic hematopoietic cell transplantation (alloHCT) and is designed to eliminate alloreactive BPX-501 T cells in the event of uncontrollable GVHD.

The clinical trials affected by this hold include the following phase I/II studies:

  • BP-001 and BP-005: adults with hematologic cancers receive BPX-501 after alloHCT
  • BP-003: children with orphan-inherited blood disorders receive BPX-501 after alloHCT
  • BP-008: adults and children with blood cancers are treated after relapsing post-transplant and evaluated for the potential for a titrated dose of rimiducid to resolve uncontrolled graft-versus-host disease (GVHD), while preserving BPX-501 cells

The clinical hold does not affect the European BP-004 trial assessing BPX-501 after alloHCT in children with hematologic cancers or orphan-inherited blood disorders.

More than 240 patients have been treated with BPX-501 after alloHCT. The drug’s manufacturer, Bellicum Pharmaceuticals, said it is waiting for formal FDA communication to determine requirements for resuming the studies.

Results from the BP-004 study, in which researchers evaluated immune recovery and outcomes of 112 pediatric patients who underwent a haploidentical HCT (haplo-HCT) followed by treatment with BPX-501, were presented at 2017 ASH Annual Meeting. At 24 months after haplo-HCT, BPX-501 cells expanded progressively, peaking at nine months after the allograft. Among 16 patients with two years of follow-up, the mean number of BPX-501 cells was 62+23/μL.

BPX-501 received orphan-drug designation in February 2016.

Sources: FierceBiotech, January 31, 2018; Merli P, Bertaina V, Galaverna F, et al. Donor T cells genetically modified with a novel suicide gene (inducible Caspase 9, iC9) expand and persist over time after post-allograft infusion in patients given αβ T-cell and B-cell depleted HLA-haploidentical allogeneic stem cell transplantation (αβ haplo-HSCT) contributing to accelerate immune recovery. Abstract #211. Presented at the 2017 American Society of Hematology Annual Meeting, December 9, 2017; Atlanta, GA.