FDA staff raise concerns about Vertex, Crispr sickle cell therapy safety data

The FDA is convening a Cellular, Tissue, and Gene Therapies Advisory Committee meeting on October 31 to discuss Vertex Pharmaceuticals’ (VRTX) analysis of off-target alterations following editing of patient hematopoietic stem and progenitor cells, or HSPCs, with clustered, regularly interspaced, short palindromic repeats-associated protein 9 nucleases, or CRISPR/Cas9, and whether it provides an adequate safety assessment. In briefing documents prepared for that meeting, FDA staff stated: “For the cellular off-target analysis, the Applicant used three samples from healthy donors and three samples from subjects with SCD of African American ethnicity. Given the impact of the SCD on HSPC function, which can potentially change the chromatin landscape and can impact off-target editing, the merits of using healthy donor samples for such analysis is not clear. Additionally, it is not clear if the small number of samples used in the cellular GUIDE-seq off-target analysis is sufficient to adequately assess off-target editing in exa-cel.” Vertex is developing for exa-cel for severe sickle cell disease in collaboration with Crispr Therapeutics (CRSP).