The FDA has expanded approval of CASGEVY (exagamglogene autotemcel) to children aged 2 years and older with sickle cell disease or transfusion-dependent beta thalassemia, supported by Phase 3 CLIMB study data demonstrating durable efficacy and a consistent safety profile.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Vertex Pharmaceuticals has received U.S. Food and Drug Administration (FDA) approval to expand the indication for CASGEVY® (exagamglogene autotemcel) to children aged 2 years and older with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) or transfusion-dependent beta thalassemia (TDT). Previously approved for patients aged 12 years and older, the one-time gene-editing therapy is now expected to make approximately 5,500 additional children in the United States eligible for treatment. According to Vertex, CASGEVY is the first approved genetic therapy for children as young as 2 years with both inherited blood disorders.
One-Time CRISPR Gene-Edited Therapy
CASGEVY is an autologous, ex vivo CRISPR/Cas9 gene-edited hematopoietic stem cell therapy that edits the erythroid-specific enhancer of the BCL11A gene in a patient’s own blood stem cells. The modification increases production of fetal hemoglobin (HbF), helping reduce red blood cell sickling in SCD and improving effective red blood cell production in patients with TDT.
Pediatric Studies Supported Expanded Approval
The expanded indication was approved through a supplemental Biologics License Application (sBLA) supported by efficacy and safety data from the Phase 3 CLIMB-151 (NCT05329649) study in pediatric SCD and the Phase 3 CLIMB-141 (NCT05477563) study in pediatric TDT. Long-term safety and durability continue to be evaluated in the ongoing CLIMB-131 (NCT04208529) follow-up study for up to 15 years after treatment.
The updated U.S. prescribing information states that the pivotal pediatric studies enrolled children aged 5 to under 12 years, while use in children aged 2 to under 5 years is supported by extrapolation of efficacy and safety data from older pediatric and adult populations.
In the pediatric SCD study, all eight efficacy-evaluable patients (8/8) achieved the primary endpoint of remaining free from severe vaso-occlusive crises for at least 12 consecutive months (VF12). In the pediatric TDT study, eight of nine efficacy-evaluable patients (8/9) achieved transfusion independence for at least 12 consecutive months (TI12) while maintaining the required weighted average hemoglobin level, demonstrating durable clinical benefit across both diseases.
Safety Profile in Younger Children
The overall safety profile in younger children was consistent with previous CASGEVY studies and reflected the known risks associated with myeloablative conditioning and autologous stem cell transplantation, with no new safety signals identified. The prescribing information includes warnings for neutrophil engraftment failure, delayed platelet engraftment, hypersensitivity reactions, and the potential risk of off-target genome editing. One patient with TDT developed veno-occlusive disease and hemophagocytic lymphohistiocytosis following busulfan conditioning and later died from pneumonia and multi-organ failure.
Regulatory Path and Access
Vertex reported that more than 75 authorized treatment centers across the United States are currently activated to provide CASGEVY through established access and reimbursement pathways. The company has also submitted applications to expand the pediatric indication in the United Kingdom and the Kingdom of Saudi Arabia, where regulatory reviews are ongoing.
The expanded approval enables earlier intervention before irreversible complications associated with recurrent vaso-occlusive crises or lifelong transfusion dependence develop, representing another important milestone in the clinical adoption of CRISPR-based gene-editing therapies for inherited blood disorders.
What This Means for Patients
The expanded FDA approval allows eligible children with sickle cell disease or transfusion‑dependent beta thalassemia to receive CASGEVY earlier in their disease course, before years of irreversible organ damage or lifelong transfusion burden accumulate. Earlier treatment may prevent recurrent vaso‑occlusive crises in sickle cell disease and enable long‑term transfusion independence in beta thalassemia, potentially improving quality of life and reducing complications.
CASGEVY is a complex, one‑time gene‑editing therapy that requires stem cell collection, myeloablative conditioning, hospitalization, and long‑term follow‑up at experienced centers. Families should discuss potential benefits, risks, eligibility, and the treatment process with their hematology and transplant teams to determine whether the therapy is an appropriate option. The expanded approval underscores both the promise and the complexity of bringing CRISPR‑based therapies into earlier pediatric care.
Reference
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.