Vertex Shares Positive Long-Term Data on CASGEVY™ at 2024 EHA Congress

Vertex Pharmaceuticals has announced promising longer-term data for CASGEVY™ (exagamglogene autotemcel [exa-cel]), a CRISPR-based gene-editing therapy, from its global clinical trials involving individuals with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT). The new data, revealed at the annual European Hematology Association (EHA) Congress, underscore the transformative, consistent, and durable benefits of CASGEVY, with patients experiencing stable fetal hemoglobin (HbF) levels and sustained allelic editing over extended periods.

The clinical trials, CLIMB-111, CLIMB-121, and CLIMB-131, involve more than 100 patients (46 with SCD and 56 with TDT). These trials have shown that the efficacy results are consistent with earlier analyses, extending the follow-up to over five years. Patients treated with exa-cel have exhibited transformative clinical benefits with durable and stable levels of fetal hemoglobin and persistent allelic editing.

Dr. Haydar Frangoul, Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute and HCA Healthcare’s TriStar Centennial Children’s Hospital, expressed optimism about offering this therapy to eligible patients, noting the significant burden faced by those living with SCD. Similarly, Dr. Franco Locatelli, Professor of Pediatrics at the Catholic University of the Sacred Heart of Rome, highlighted the importance of making this innovative treatment available in the real world, emphasizing the durable benefits observed in patients.

The data presented from CASGEVY pivotal trials demonstrated impressive results. In SCD patients, 92.3% (36/39) of evaluable patients were free from vaso-occlusive crises (VOCs) for at least 12 consecutive months (VF12), with a mean VOC-free duration of 27.9 months, and up to 54.8 months. Additionally, 97.4% (38/39) were free from hospitalizations related to VOCs for at least 12 consecutive months (HF12). For TDT patients, 94.2% (49/52) were transfusion-independent for at least 12 consecutive months with a mean weighted hemoglobin of at least 9 g/dL (TI12), and a mean transfusion independence duration of 31.0 months, reaching up to 59.4 months. Notably, all TDT patients with at least 16 months of follow-up are transfusion-free.

Patients in both SCD and TDT groups reported significant long-term improvements in quality of life, including physical, emotional, social, and functional well-being. The stability of edited BCL11A alleles in both bone marrow and peripheral blood indicates successful long-term hematopoietic stem cell editing. Moreover, all patients successfully engrafted neutrophils and platelets post-exa-cel infusion, with the safety profile consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant.

The data from these trials will be shared through oral and poster presentations at the EHA Congress. Specifically, oral presentations will occur on June 16, covering the effectiveness of exa-cel in treating severe sickle cell disease and transfusion-dependent beta-thalassemia. Poster presentations will take place on June 14, focusing on health-related quality of life improvements after exa-cel treatment in patients with these conditions.

Sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT) are serious genetic disorders that significantly impair patients' quality of life and require extensive medical care and resources. SCD is marked by severe pain and organ damage due to misshapen red blood cells, while TDT necessitates frequent blood transfusions and iron chelation therapy. Both conditions result in reduced life expectancy and quality of life. The lack of available stem cell donors limits the curative options for these diseases.

CASGEVY™ represents a breakthrough in gene-editing therapies, potentially reducing or eliminating VOCs in SCD patients and transfusion needs in TDT patients by increasing fetal hemoglobin levels. The ongoing CLIMB studies continue to evaluate the long-term safety and efficacy of CASGEVY, with patients being monitored for up to 15 years post-infusion.