FDA to Review Vertex Pharmaceutical’s Application for CRISPR-based Gene Therapy Exa-cel

The Cellular, Tissue, and Gene Therapies Advisory Committee of the FDA is meeting tomorrow, Tuesday, October 31, 2023, to review a Biologics License Application by Vertex Pharmaceuticals Inc. for exagamglogene autotemcel (exa-cel).  Exa-cel is a cell-based gene therapy product composed of the patient’s own hematopoietic stem and progenitor cells (HSPCs) edited at the BCL11A gene with a CRISPR/Cas9 construct. The therapy is currently being studied in clinical trials for the treatment of severe sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT).  At the meeting, the Committee will discuss Vertex’s analysis of off-target alterations following editing of patient HSPCs with CRISPR/Cas9, and whether Vertex has produced an adequate safety assessment of off-target effects for patients with sickle cell disease.


On June 8, 2023, Vertex and CRISPR Therapeutics announced that the FDA had accepted the BLA for Exa-cel.  According to Vertex, the FDA granted Priority Review for SCD and Standard Review for TDT, and assigned Prescription Drug User Fee Act (PDUFA) target action dates of December 8, 2023, and March 30, 2024, respectively.  Vertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease.  According to the press release, Exa-cel represents the first potential treatment to emerge from the joint research program.