Positive long-term data on Casgevy (exagamglogene autotemcel) presented at the 2024 Annual European Hematology Association (EHA) Congress.- Vertex Pharma

The results, presented at the annual European Hematology Association (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 (46 SCD; 56 TDT) treated with exa-cel in clinical trials, with the longest follow-up now extending more than 5 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 (HbF) and allelic editing.

“The transformative benefit seen in patients with sickle cell disease in the trial is impressive given the significant and cumulative burden of disease faced by people living with this blood disorder,” said Haydar Frangoul, M.D., M.S., Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute and HCA Healthcare’s TriStar Centennial Children’s Hospital. “I am eager to offer this therapy and the opportunity of a potential functional cure to my eligible patients.”

“The comprehensive data set presented for adult and adolescent TDT patients adds to the growing body of evidence for Casgevy, and it is important to now ensure the availability of this innovative treatment to patients in the real world as soon as possible,” 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. “With the longest follow up now more than five years, alongside stable editing and sustained fetal hemoglobin levels, I have conviction in the durable benefit to the patients treated with CASGEVY.”

New data presented from Casgevy pivotal trials: : i. In SCD 36/39 (92.3%) evaluable patients (those with at least 16 months of follow-up) were free from vaso-occlusive crises (VOCs) for at least 12 consecutive months (VF12), consistent with the previously reported primary endpoint data. Mean duration of VOC-free was 27.9 months, with a maximum of 54.8 months. a. 38/39 (97.4%) patients with at least 16 months of follow-up were free from hospitalizations related to VOCs for at least 12 consecutive months (HF12), consistent with the previously reported key secondary endpoint data. ii. In TDT 49/52 (94.2%) evaluable patients (those with at least 16 months of follow-up) were transfusion-independent for at least 12 consecutive months with a mean weighted hemoglobin of at least 9 g/dL (TI12), consistent with the previously reported primary endpoint data. Mean duration of transfusion independence was 31.0 months, with a maximum of 59.4 months. iii. 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. iv. 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.

These longer-term data for Casgevy from the CLIMB clinical trials will be shared as outlined below: i. Abstracts S273 and S274 will be oral presentations entitled “Exagamglogene Autotemcel For Severe Sickle Cell Disease,” and “Exagamglogene Autotemcel For Transfusion-Dependent Beta-Thalassemia,” on Sunday, June 16 at 12:15 CEST and 12:30 CEST, respectively. ii. Abstracts P1493 and P1525 will be poster presentations entitled “Health-Related Quality Of Life Improvements After Exagamglogene Autotemcel In Patients With Severe Sickle Cell Disease,” and “Health-Related Quality Of Life Improvements After Exagamglogene Autotemcel In Patients With Transfusion-Dependent ?eta-Thalassemia,” on Friday, June 14 at 18:00 CEST. iii. These presentations will include updated pivotal trial data from patients treated with CASGEVY in CLIMB-111 and CLIMB-121 and followed in CLIMB-131.