Vertex Pharmaceuticals presents long-term Casgevy trial data

Vertex Pharmaceuticals announced longer-term data for Casgevy from global clinical trials in people with severe sickle cell disease, or SCD, or transfusion-dependent beta thalassemia, or TDT. The results, presented at the annual European Hematology Association, or EHA, Congress, confirm the transformative, consistent and durable clinical benefits of Casgevy over time. Casgevy is the first and only approved CRISPR-based gene-editing therapy. The data being presented are from more than 100 patients treated with exa-cel in clinical trials, with the longest follow-up now extending more than five years. The efficacy results are consistent with the previously reported primary and key secondary endpoints analyses from these exa-cel studies and continue to demonstrate transformative clinical benefit with durable and stable levels of fetal hemoglobin and allelic editing. In SCD 36/39 evaluable patients were free from vaso-occlusive crises, or VOCs, for at least 12 consecutive months, consistent with the previously reported primary endpoint data. Mean duration of VOC-free was 27.9 months, with a maximum of 54.8 months. 38/39 patients with at least 16 months of follow-up were free from hospitalizations related to VOCs for at least 12 consecutive months, consistent with the previously reported key secondary endpoint data. In TDT 49/52 evaluable patients were transfusion-independent for at least 12 consecutive months with a mean weighted hemoglobin of at least 9 g/dL, consistent with the previously reported primary endpoint data. Mean duration of transfusion independence was 31 months, with a maximum of 59.4 months. All TDT patients dosed with at least 16 months of follow up are transfusion free. Two of the three patients who did not achieve TI12 in CLIMB-111 achieved TI12 in the long-term follow-up study, CLIMB-131, and have been transfusion independent for over one year. The third has been transfusion free for 3.4 months. Both SCD and TDT patients reported sustained and clinically meaningful improvements in their quality of life, including physical, emotional, social/family and functional well-being, and overall health status. In both SCD and TDT patients, edited levels of BCL11A alleles were stable over time in bone marrow and peripheral blood indicating successful editing in the long-term hematopoietic stem cells. All patients engrafted neutrophils and platelets after exa-cel infusion. The safety profile of exa-cel was generally consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant.