The US FDA has supplementally approved Casgevy (exagamglogene autotemcel) for patients aged 2 years and older with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) or transfusion-dependent β-thalassemia (TDT) — marking the first gene therapy approved for young children with SCD. Vertex Pharmaceuticals received the approval, which extends a label previously restricted to patients aged 12 years and older, and was processed in 53 days under the FDA Commissioner’s National Priority Voucher pilot program.
Casgevy is a one-time autologous cell therapy administered as a single intravenous infusion following full myeloablative conditioning. It uses CRISPR/Cas9 genome editing to disrupt the BCL11A erythroid enhancer in the patient’s own hematopoietic stem cells, reactivating fetal hemoglobin (HbF) production — the scientific basis for which was recently recognized with a Breakthrough Prize. Elevated HbF prevents red blood cells from adopting the sickle morphology that drives VOCs in SCD and reduces transfusion dependence in TDT.
The supplemental approval was supported by two pediatric cohort studies in patients aged 5 to under 12 years. In the SCD trial (11 patients), all eight efficacy-evaluable patients achieved the primary endpoint of VF12 — defined as freedom from protocol-defined severe VOCs for at least 12 consecutive months within 24 months post-infusion. In the TDT trial (15 patients), eight of nine efficacy-evaluable patients achieved transfusion independence for 12 consecutive months, with a median duration of 20.1 months. The FDA extended the approved age range to 2 years based on extrapolation from product characteristics and these pediatric data. The most common adverse reactions were mucositis and febrile neutropenia; prescribing information carries warnings for neutrophil engraftment failure, delayed platelet engraftment, hypersensitivity reactions, and off-target genome editing risk.