FDA Expands Exa-Cel Gene Therapy Approval to Children 2 Years and Up With SCD or β-Thalassemia

The US Food and Drug Administration (FDA) on July 1, 2026, granted supplemental approval to exagamglogene autotemcel (Casgevy; Vertex Pharmaceuticals) for patients aged 2 years and older with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) or transfusion-dependent β-thalassemia (TDT), extending an indication previously limited to patients aged 12 and older.¹ The action makes exa-cel the first gene therapy approved for young children with SCD and the first CRISPR-based gene-editing therapy to reach this age group in either condition.

The supplemental approval was reviewed in 53 days following filing as the eighth therapy selected under the FDA Commissioner's National Priority Voucher pilot program, which is designed to accelerate review of treatments for diseases with significant unmet medical need.¹ Exa-cel previously received Orphan Drug, Regenerative Medicine Advanced Therapy (RMAT), and Fast Track designations.

Mechanism and administration

Exa-cel is an autologous cell therapy manufactured from a patient's own hematopoietic stem and progenitor cells, which are edited ex vivo using CRISPR/Cas9 technology to reactivate fetal hemoglobin (HbF) production by targeting the erythroid enhancer region of BCL11A. In SCD, increased HbF inhibits red blood cell sickling, reducing or eliminating VOCs. In TDT, elevated HbF and total hemoglobin levels eliminate dependence on regular red blood cell transfusions. Exa-cel is administered as a 1-time intravenous infusion; full myeloablative conditioning with busulfan is required prior to infusion and engraftment in bone marrow.¹

Pediatric efficacy data

Efficacy and safety in children aged 5 to less than 12 years with SCD were evaluated in a clinical trial enrolling 11 patients. All 8 efficacy-evaluable patients achieved the primary endpoint of VF12 — defined as freedom from protocol-defined severe VOCs for at least 12 consecutive months within the first 24 months post-infusion.¹ In the corresponding TDT trial in the same age group (n = 15), 8 of 9 efficacy-evaluable patients achieved transfusion independence for at least 12 consecutive months, with a median duration of transfusion independence of 20.1 months.¹

Clinicians should note that both pediatric cohorts were small, and the FDA's decision to extend the indication to patients as young as 2 years was granted by extrapolation based on product characteristics and clinical study data from the 5–<12 age group, not from direct trial evidence in children aged 2–4.¹ These data build on the earlier CLIMB SCD-121 pivotal trial in patients aged 12–35, in which 96.7% of efficacy-evaluable participants remained free of VOCs for at least 12 consecutive months following treatment, as reported in the New England Journal of Medicine in 2024.²

Safety profile and labeled warnings

The most common adverse events in both indications were mucositis and febrile neutropenia. Decreased appetite was additionally reported in patients with SCD. The exa-cel prescribing information carries warnings for neutrophil engraftment failure, delayed platelet engraftment, and hypersensitivity reactions. Of particular clinical significance is a warning for off-target genome editing risk — the possibility that CRISPR/Cas9 may introduce unintended edits to parts of the genome outside the intended target site; the long-term clinical consequences of such edits are not yet fully characterized.¹ Patients are planned to be followed for up to 15 years post-infusion in long-term safety studies.

"These disorders carry a heavy burden for children and their families, affecting growth, development, and long-term health in profound ways," said Megha Kaushal, MD, MSc, acting deputy director of the Office of Therapeutic Products in the FDA's Center for Biologics Evaluation and Research and a pediatric hematologist. "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."¹

References

1. US Food and Drug Administration. FDA approves first gene therapy for young children with sickle cell disease. Press release. July 1, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-young-children-sickle-cell-disease

2. Frangoul H, Locatelli F, Sharma A, et al. Exagamglogene autotemcel for severe sickle cell disease. N Engl J Med. 2024;390(18):1649-1662. doi:10.1056/NEJMoa2309676