Sickle Cell Gene Therapy: FDA Likely Set to Approve

A new drug that uses the CRISPR gene-editing tool to treat sickle cell disease is likely one step closer to Food and Drug Administration (FDA) approval, after a key agency advisory committee expressed optimism about the treatment.

The drug uses gene-editing technology developed through a collaboration between Vertex Pharmaceuticals and CRISPR Therapeutics. The FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee did not vote during its Tuesday meeting, but the positive discussion likely signals the agency will make a favorable decision.

“Especially given the benefits of this treatment or this cure and what these patients are dealing with without having this treatment, I think the benefits far outweigh the risks here,” said Alexis Komor, committee member and head of her own gene-editing lab at the University of California, San Diego.

Fellow committee member Lisa Lee, associate vice president for research and innovation at Virginia Tech, said the evidence of the treatment’s efficacy was “overwhelming.”

This would mark the first time the FDA approved a drug that uses CRISPR technology. Given the relative novelty of this treatment, several members questioned what level of risk would be tolerable, how those risks could be determined and how they can be mitigated.

One risk that was heavily discussed was off-target editing, or unintended genetic modifications using the technology. Vertex and CRISPR told the committee they had not detected this side effect in their treatment.

The one-time treatment is referred to as exagamglogene autotemcel (exa-cel).

It involves taking a patient’s own stem cells, editing them to fix the genetic problems that create sickle cell disease and producing high levels of fetal hemoglobin, the oxygen-carrying protein present during fetal development.

According to CRISPR, elevating levels of fetal hemoglobin could reduce the severity of sickle cell disease in patients.

A bone marrow transplant is currently the only cure for sickle cell disease. The best match for a patient is usually a fully related sibling, though even full siblings only have a 1 in 4 chance of being a match.

Sickle cell disease is a genetic condition that causes normally disc-shaped red blood cells to be sickle or crescent-shaped. These cells don’t bend or move like normal red blood cells and can block blood flow to organs.

The lack of options for sickle cell disease was frequently brought up during the all-day meeting. FDA has called it an “unmet medical need.”

The FDA is expected to make an approval decision by Dec. 8.