CRISPR Therapeutics announced that the FDA's Cellular, Tissue, and Gene Therapies Advisory Committee had held its meeting for exagamglogene autotemcel (exa-cel), designed to treat severe sickle cell disease (SCD) in individuals aged 12 and older experiencing recurrent vaso-occlusive crises (VOCs).
Exa-cel, previously named CTX001, is an experimental CRISPR-based hematopoietic stem cell therapy designed for individuals with severe hemoglobin disorders. Its IND application was presented to the FDA in April 2018, and within a month, Vertex disclosed a temporary hold, which was pending the clarification of specific inquiries from the FDA as part of its review. The hold was lifted just a few months later, and the companies continued pursuing approvals of clinical trial applications for CTX001 in multiple countries outside the U.S. for both β-thalassemia and SCD.
In the recent AdComm meeting, members closely focused on the data concerning off-target risks, and eventually expressed reservations about the company's capacity to evaluate risk across a wide population. However, when it came to efficacy, there were fewer concerns among the members.
The drug marks the first therapeutic product arising from the collaboration between CRISPR Therapeutics and Vertex Pharmaceuticals established in 2015. If approved, exa-cel would be the first genetic therapy for the roughly 20,000 severe SCD patients in the U.S. The FDA granted priority review status for exa-cel in SCD treatment, setting a PDUFA action date of December 8, 2023. Furthermore, the BLA for exa-cel in transfusion-dependent beta-thalassemia (TDT) is scheduled for PDUFA review on March 30, 2024.