CASGEVY Extends Durable Clinical Benefit to Children With SCD and TDT

Phase 3 studies presented at EHA 2026 showed that CASGEVY® (exagamglogene autotemcel) enabled all evaluable children aged 5–11 years with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT) to achieve the primary efficacy endpoints, supporting expansion of the CRISPR-based therapy into younger pediatric populations.

In the Phase 3 CLIMB-151 study (NCT05329649), all 11 treated children with SCD remained free of vaso-occlusive crises (VOCs). Among the eight patients with sufficient follow-up, 100% achieved the primary endpoint of being VOC-free for at least 12 consecutive months (VF12). The mean duration of VOC-free status was 19.0 months, with follow-up extending to 30.1 months.

In the Phase 3 CLIMB-141 study (NCT05356195), 15 children with TDT received CASGEVY. All eight evaluable patients achieved the primary endpoint of transfusion independence for at least 12 consecutive months while maintaining a weighted average hemoglobin level of at least 9 g/dL. The mean duration of transfusion independence was 23.4 months, with sustained benefit throughout follow-up.

Biological Correlates Support Durability

Investigators reported durable increases in fetal hemoglobin (HbF) levels and stable allelic editing across both studies, supporting the long-term biological activity of CASGEVY. The therapy edits the erythroid-specific enhancer of the BCL11A gene, enabling sustained HbF production to reduce red blood cell sickling in SCD and improve ineffective erythropoiesis in TDT.

These findings are consistent with the durable efficacy profile previously reported in adolescent and adult patients treated with CASGEVY.

Safety Profile Consistent with Conditioning

The safety profile remained consistent with expectations for myeloablative conditioning and autologous stem cell transplantation. No new safety signals were identified.

One death occurred in a child with TDT who developed severe veno-occlusive disease following busulfan conditioning. Investigators previously reported that the event was not related to CASGEVY.

Regulatory Expansion Underway

CASGEVY is currently approved in multiple countries for eligible patients aged 12 years and older with SCD and recurrent VOCs or TDT. Regulatory reviews are now progressing to extend use into younger pediatric populations.

In the United States, the FDA is reviewing a pediatric expansion application after Vertex received a Commissioner’s National Priority Voucher. The company has also completed submissions in the United Kingdom and Saudi Arabia seeking approval for use in children aged 5–11 years.

Earlier access to treatment could help prevent irreversible complications that accumulate throughout childhood in both diseases.

Program Status and Long-Term Follow-Up

Enrollment and dosing are complete for the 5–11-year-old cohorts of CLIMB-141 and CLIMB-151. Long-term follow-up continues through the CLIMB-131 study, which is evaluating the durability, efficacy, and safety of CASGEVY for up to 15 years after treatment.

Commenting on the findings, Vertex Chief Medical Officer Dr. Carmen Bozic said the results reinforce the durable and clinically meaningful benefits observed across age groups.

Presenting investigator Dr. Franco Locatelli highlighted the potential of earlier intervention to reduce disease burden and alter long-term outcomes for children living with SCD and TDT.

Reference

Vertex Presents New Data on CASGEVY®, Including First European Presentation of Data in Children Ages 5–11, at the European Hematology Association Congress and Announces Additional Global Regulatory Submissions | Vertex Pharmaceuticals Newsroom