Vertex Pharmaceuticals announced positive longer-term efficacy data for CASGEVY (exagamglogene autotemcel), the first authorized CRISPR/Cas9 gene-edited therapy, at the 2025 European Hematology Association Congress. The data from ongoing pivotal clinical trials in patients with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT) demonstrate sustained clinical benefits with the longest follow-up now extending more than 5.5 years in SCD patients and more than 6 years in TDT patients.
Sustained Efficacy in Sickle Cell Disease
The longer-term follow-up data from the combined CLIMB-121 and CLIMB-131 trials showed remarkable durability in SCD patients. Among 45 evaluable patients with at least 16 months of follow-up, 43 patients (95.6%) remained free from vaso-occlusive crises (VOCs) for at least 12 consecutive months (95% CI: 84.9%, 99.5%). The mean duration of VOC-free period was 35.0 months, with a range extending from 14.4 to 66.2 months.
Even more striking, all evaluable patients (45/45, 100%) achieved freedom from in-patient hospitalization for severe VOCs for at least 12 consecutive months (95% CI: 92.1%, 100%). The mean hospitalization-free duration was 36.1 months, ranging from 14.5 to 66.2 months.
Transfusion Independence in Beta Thalassemia
In TDT patients, the therapy demonstrated equally impressive results. Among 55 evaluable patients from the combined CLIMB-111 and CLIMB-131 trials, 54 patients (98.2%) achieved transfusion independence for at least 12 consecutive months while maintaining a weighted average hemoglobin of at least 9 g/dL (95% CI: 90.3%, 100%). The mean duration of transfusion independence was 40.5 months, with a range of 13.6 to 70.8 months.
The single evaluable patient who did not achieve the 12-month transfusion independence milestone has still been transfusion-free for 14.8 months. Additionally, iron removal therapy was discontinued for more than 6 months in 39 of 56 treated patients (69.6%) following CASGEVY infusion, with sustained improvements in ferritin and liver iron content.
Mechanism and Safety Profile
CASGEVY works as an autologous genome-edited hematopoietic stem cell-based therapy, where patients' own hematopoietic stem and progenitor cells are edited at the erythroid-specific enhancer region of the BCL11A gene through a precise double-strand break. This editing results in the production of high levels of fetal hemoglobin (HbF) in red blood cells, which is the form of oxygen-carrying hemoglobin naturally present during fetal development.
Patients continue to demonstrate stable levels of fetal hemoglobin and allelic editing throughout the follow-up period. The safety profile of CASGEVY remains generally consistent with myeloablative conditioning using busulfan and autologous hematopoietic stem cell transplant.
Expanding Global Access
Vertex has made significant progress in securing patient access through reimbursement agreements across multiple countries, including Austria, Bahrain, England, Denmark, the Kingdom of Saudi Arabia, Northern Ireland, Scotland, the United Arab Emirates, the United States, and Wales.
In Canada, CASGEVY received positive recommendations for reimbursement from both Canadian health technology agencies between December 2024 and January 2025, though a Letter of Engagement from the pan-Canadian Pharmaceutical Alliance (pCPA) remains pending.
Clinical Impact and Expert Perspective
"This longer-term data reinforces CASGEVY's durable clinical benefits for eligible people living with sickle cell disease or transfusion-dependent beta thalassemia," said Kevin Kuo, M.D., Hematologist and Associate Professor in the Division of Hematology at the University of Toronto, Clinician Investigator in the Red Blood Cell Disorders Clinic at University Health Network, and Principal Investigator for the CLIMB-131 clinical program. "These results are a reminder of what science can achieve, especially for patients and communities with significant unmet need."
Study Design and Future Monitoring
The ongoing Phase 1/2/3 open-label trials CLIMB-111 and CLIMB-121 assessed the safety and efficacy of a single dose of CASGEVY in patients aged 12 to 35 years with TDT or SCD with recurrent VOCs. While these trials are closed for enrollment, patients are followed for approximately two years after CASGEVY infusion and then invited to participate in CLIMB-131, a long-term follow-up study designed to evaluate safety and efficacy for up to 15 years after treatment.
The sustained efficacy demonstrated in these longer-term follow-up studies represents a significant advancement for patients with these debilitating genetic diseases, both of which require lifelong treatment and result in reduced life expectancy, decreased quality of life, and significant healthcare resource utilization.
