Update on Gene Therapy and Genome-Editing for Rare Diseases

On Friday, June 10, 2022 an FDA advisory panel gave a unanimous recommendation for approval to a gene therapy called beti-cel from Bluebird Bio, endorsing a one-time treatment for sickle cell or beta-thalassemia, a rare blood disorder that requires frequent blood transfusions.

The group of independent experts voted 13-0 that the benefits of the gene therapy outweigh its risks for patients with beta-thalassemia, a disease that leads to severe anemia and requires patients to undergo frequent blood transfusions. The FDA is not required to follow the recommendations of its advisers, though it typically does. The agency has promised to render a final decision on beti-cel, by August 19.

The therapy beta-thalassemia uses CRISPR technology to genetically fix diseased cells caused by mutations in the gene responsible for producing oxygen-carrying hemoglobin. The goal of the therapy is to increase production of fetal hemoglobin, which normally shuts down soon after birth.

CRISPR genome editing allows scientists to quickly create cell and animal models, which researchers can use to accelerate research into diseases such as cancer and mental illness. In addition, CRISPR is now being developed as a rapid diagnostic.

On Thursday, the same panel voted in favor of eli-cel, Bluebird’s one-time treatment for cerebral adrenoleukodystrophy, a rare neurological disorder. FDA scientists had been skeptical of eli-cel’s efficacy and alarmed by its cancer risk, but Nirali Shah, a pediatric oncologist at the National Cancer Institute, said, “I still think that the benefit to eli-cel is greater.”

Small Patient Populations

Neither drug is expected to become a top-seller, since the pool of patients who would be eligible for eli-cel is tiny -- about 10 per year. Estimates for beti-cel are larger, but still modest, numbering between 1,000 to 1,300 patients with severe beta thalassemia who could receive beti-cel.

If approved, eli-cel and beti-cel would become the third and fourth gene therapies cleared in the U.S. for inherited diseases, after Roche’s Luxturna and Novartis’ Zolgensma.