Questions Surround Vertex/CRISPR's Sickle Cell Gene Therapy As FDA AdComm Meeting Approaches

The FDA's Cellular, Tissue, and Gene Therapies Advisory Committee will meet next week, Tuesday, 31 October, to discuss whether Vertex Pharmaceuticals Inc VRTX and CRISPR Therapeutics AG's CRSP sickle cell disease (SCD) gene therapy candidate.

While the agency did not raise any concerns regarding the efficacy of the therapy, dubbed exagamglogene autotemcel (exa-cel), the FDA questioned whether Vertex used an appropriate sample size for its off-target editing analysis, according to FDA briefing documents released.

Also Read: Mixed Signals For CRISPR Therapeutics, Analyst Weighs Barriers, Potential Sales For Sickle Cell Therapy.

The agency noted that "it is not clear if the limited SCD donor cells used for the off-target assessment will adequately inform the potential safety risks of exa-cel."

FDA also noted that Vertex and CRISPR used the 1,000 Genomes Project database, with its whole genome sequencing (WGS) data for 2,504 individuals, but only 61 WGS datasets were collected in the U.S., and all datasets were from individuals who were located in the southwest U.S.

"The small target sample size (61 WGS datasets) in this database may not be sufficient for the safety assessment as it may not adequately capture variants in this population across the United States," the FDA said.

"Given the large number of patients in the U.S. who are the intended target population for this drug, it is not clear if the sequencing information from the limited number of individuals captured in the 1,000 genomes project reference database would sufficiently capture variants that may contribute to an off-target locus," the briefing documents add.

The FDA decision date is set for 8 December for the therapy's use in patients aged 12 years and older.

William Blair sees the AdCom briefing documents as a highly favorable situation for CRISPR/Vertex. 

The analyst expects the emphasis to be on the safety profile and unique mechanism of action of exa-cel, as it's the first CRISPR-based therapy and gene therapy for SCD undergoing FDA evaluation for approval. 

However, the primary concern for investors is whether the FDA will demand further analyses and, if required, whether the companies can produce the necessary data post-approval.

Price Action: VRTX shares are down 1.09% at $357.33 on the last check Friday.