Vertex Pharmaceuticals presented long-term data at the American Society of Hematology (ASH) Annual Meeting, showcasing the durable clinical benefits of CASGEVY™ (exagamglogene autotemcel) in patients with severe sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT). CASGEVY, the first approved CRISPR/Cas9 gene-edited therapy, continues to demonstrate transformative outcomes with follow-up extending beyond five years.
Sustained VOC-Free Status in SCD Patients
In the SCD cohort, 39 out of 42 (93%) evaluable patients from the CLIMB-121 and CLIMB-131 trials remained free from vaso-occlusive crises (VOCs) for at least 12 consecutive months (VF12). The mean duration of VOC-free status was 30.9 months, with some patients experiencing up to 59.6 months without VOCs. Even among the three patients who did not achieve VF12, significant clinical benefits were observed, including reductions in hospitalization rates for VOCs by 91%, 71%, and 100%.
Transfusion Independence in TDT Patients
For patients with TDT, 53 out of 54 (98%) evaluable patients achieved transfusion independence for at least 12 consecutive months (TI12) with a weighted average hemoglobin level of at least 9 g/dL. The mean duration of transfusion independence was 34.5 months, with a maximum of 64.1 months. The single patient who has not yet achieved TI12 has been transfusion-free for 8.2 months.
Improvements in Quality of Life
Both SCD and TDT patients reported sustained and clinically meaningful improvements in their quality of life, encompassing physical, emotional, social/family, and functional well-being, as well as overall health status. These improvements highlight the comprehensive benefits of CASGEVY beyond clinical endpoints.
Safety Profile and Global Access
The safety profile of CASGEVY remains consistent with myeloablative conditioning using busulfan and autologous hematopoietic stem cell transplant. Patients continue to exhibit stable levels of fetal hemoglobin (HbF) and allelic editing across all ages and genotypes.
CASGEVY has been approved for both SCD and TDT in multiple regions, including the U.S., European Union, Great Britain, Canada, Switzerland, Bahrain, and the Kingdom of Saudi Arabia. Vertex is actively working to secure reimbursement agreements and expand access to patients worldwide, with over 45 authorized treatment centers activated globally and more than 40 patients having undergone initial cell collection. Agreements to provide CASGEVY are in place in several countries, including the U.S., England (for TDT), Austria, Bahrain, and the Kingdom of Saudi Arabia. A voluntary agreement with the Centers for Medicare & Medicaid Services (CMS) in the U.S. aims to ensure broad and equitable access to CASGEVY for Medicaid programs.
"These comprehensive data provide additional evidence of the benefits of eradicating transfusion requirements for people with transfusion-dependent beta thalassemia and vaso-occlusive crises for those with sickle cell disease," said Franco Locatelli, M.D., Ph.D., Professor of Pediatrics at the Catholic University of the Sacred Heart of Rome, Director of the Department of Pediatric Hematology and Oncology at Bambino Gesù Children’s Hospital, Chair of Vertex’s TDT Program Steering Committee. "With median follow-up around three years there is strong evidence for the durability of these beneficial effects following treatment with CASGEVY."
Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex, added, "CASGEVY is changing the outlook for people living with sickle cell disease and beta thalassemia, with these data reinforcing the immense clinical value a durable one-time therapy can provide to patients. We have a strong commitment to build on our progress in bringing CASGEVY to patients around the world."
