A potential 1-time gene editing treatment for severe sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) is entering approval review by the US Food and Drug Administration (FDA), the European Medicines Agency, and the UK Medicines and Healthcare products Regulatory Agency, according to a company statement.

Both diseases involve variants in the gene encoding β globin. The variants damage β globin in patients with SCD and reduce or eliminate it in patients with TDT. With exagamglogene autotemcel treatment, called exa-cel by developers Vertex Pharmaceuticals and CRISPR Therapeutics, the patient’s own hematopoietic stem cells are harvested and gene edited to produce high levels of fetal hemoglobin (HbF) in red blood cells. The edited cells are then infused back into the patient as part of an autologous hematopoietic stem cell transplant.

The treatment is intended to increase production of HbF, which normally decreases dramatically during infancy. Doing so should raise HbF and total hemoglobin levels, reducing the need for transfusions among patients with TDT and vaso-occlusive episodes among patients with SCD.

Interim results from the first 75 patients in 2 ongoing pivotal trials showed a single dose of exa-cel eliminated the need for red blood cell transfusions among 42 of 44 patients with TDT and reduced them more than 70% among the other 2 patients. Severe vaso-occlusive episodes were eliminated after treatment among 31 patients with SCD. The results were presented at the European Hematology Association Congress in June 2022 by Prof. Franco Locatelli.

The study participants were followed up from 1.2 months to 37 months after infusion. Among the patients with TDT followed up for more than 3 months, HbF levels eventually increased to about 40% of total hemoglobin. Both groups’ average total hemoglobin levels increased to greater than 11 g/dL for the duration of follow-up. Two patients with TDT had serious treatment-related adverse events.

“By reactivating a naturally occurring developmental process, exa-cel restores fetal hemoglobin production and thereby can ameliorate the course of these diseases,” investigator Haydar Frangoul, MD, medical director of pediatric hematology and oncology at TriStar Centennial Medical Center, said in a company statement.

The European and UK data submissions are expected by the end of this year, while the FDA rolling review submission is targeted for completion in early 2023, the company said.

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