The US Food and Drug Administration has approved an expanded indication for exagamglogene autotemcel (CASGEVY) to include patients aged 2 years and older with sickle cell disease and recurrent vaso-occlusive crises or transfusion-dependent beta thalassemia, according to a press release from Vertex Pharmaceuticals.

“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,” said Haydar Frangoul, MD, MS, medical director of HCA Healthcare’s Sarah Cannon Transplant and Cellular Therapy Program at TriStar Centennial Children's Hospital, an investigator with Sarah Cannon Research Institute and a member of Vertex's sickle cell disease (SCD) Program Steering Committee.

CASGEVY is a nonviral, ex vivo CRISPR/Cas9 gene-edited cell therapy that modifies a patient's hematopoietic stem and progenitor cells by editing the erythroid-specific enhancer of the BCL11A gene to increase fetal hemoglobin production. According to Vertex, clinical trials showed the therapy reduced or eliminated vaso-occlusive crises in patients with SCD and reduced transfusion requirements in patients with transfusion-dependent beta thalassemia (TDT).

The expanded approval follows the completed phase 1/2/3 open-label CLIMB-111 and CLIMB-121 studies in patients aged 12 to 35 years. Ongoing phase 3 CLIMB-141 and CLIMB-151 studies are evaluating CASGEVY in patients aged 2 to 11 years. Vertex said enrollment and dosing have been completed in the cohort aged 5 to 11 years in both studies. The ongoing CLIMB-131 study is evaluating the long-term safety and efficacy of CASGEVY with follow-up of up to 15 years following infusion.

Vertex stated that approximately 5,500 additional pediatric patients in the US are now eligible for treatment and that more than 75 independently operated authorized treatment centers have been activated across the US. Vertex reported that the proposed label expansion is under regulatory review in the United Kingdom and the Kingdom of Saudi Arabia.

The prescribing information includes warnings regarding neutrophil engraftment failure, delayed platelet engraftment, hypersensitivity reactions, and potential off-target genome editing. The most common grade 3 or 4 nonlaboratory adverse reactions, reported in at least 25% of patients, were mucositis and febrile neutropenia among patients with SCD or TDT and decreased appetite among patients with SCD. In clinical trials, all treated patients with SCD and TDT experienced grade 3 or 4 neutropenia and thrombocytopenia.

Source: Vertex Pharmaceuticals