The U.S. Food and Drug Administration (FDA) expanded the approval for exagamglogene autotemcel (exa-cel, Casgevy) to include children aged 2 years and older with severe sickle cell disease featuring recurrent vaso-occlusive crises and transfusion-dependent beta thalassemia. Exa-cel represents the first FDA-approved therapy that utilizes CRISPR/Cas9 gene-editing technology.

Previously, exa-cel had only received approval for adults and pediatric patients who were 12 years of age and older. Megha Kaushal, acting deputy director of the Office of Therapeutic Products in the FDA's Center for Biologics Evaluation and Research, stated, "These disorders carry a heavy burden for children and their families, affecting growth, development, and long-term health in profound ways." Kaushal added, "Grounded in the scientific evidence that earlier treatment reduces the risk of lasting end-organ damage, making this therapy available to younger patients opens a critical window for intervention and gives these children a meaningful chance at a healthier future."

The expanded approval was based on results from two clinical trials, CLIMB SCD-151 and CLIMB THAL-141. These results were initially reported at the American Society of Hematology annual meeting. Haydar Frangoul, lead investigator of both the CLIMB SCD-151 and CLIMB THAL-141 studies, said, "Today's approval offers renewed hope for children living with sickle cell disease or transfusion‑dependent beta thalassemia." He added, "Earlier access to the transformative potential of this therapy will allow clinicians and families to consider treatment before years of cumulative damage from these life-shortening diseases take hold."

CLIMB SCD-151 included 11 patients between the ages of 5 and 11 years with sickle cell disease. All eight evaluable patients in this trial were free of vaso-occlusive crises for at least 12 consecutive months within the first 24 months after receiving an exa-cel infusion. CLIMB THAL-141 involved 15 patients aged 5 to 11 years with transfusion-dependent beta thalassemia. Eight of the nine efficacy-evaluable patients in CLIMB THAL-141 achieved transfusion independence for 12 consecutive months, with a median duration of transfusion independence of 20.1 months.

Exa-cel consists of the patient's own hematopoietic blood stem cells, which are edited using CRISPR/Cas9 technology and then engrafted into the body's bone marrow. The therapy is administered as a one-time single dose for intravenous infusion. Common adverse reactions observed with exa-cel include mucositis and febrile neutropenia in patients with both diseases, and decreased appetite in those with sickle cell disease. The prescribing information for exa-cel includes warnings regarding neutrophil engraftment failure, delayed platelet engraftment, hypersensitivity reactions, and the risk of off-target genome editing.