Today, Vertex announced longer-term data for CASGEVY™ (exagamglogene autotemcel [exa-cel]) from global clinical trials involving individuals with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT). 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 presented data include more than 100 patients (46 SCD; 56 TDT) treated with exa-cel in clinical trials, with follow-up extending over five years. The efficacy results align with previously reported primary and key secondary endpoint analyses, demonstrating durable clinical benefits with 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 today 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.”
Key Data from CASGEVY Pivotal Trials:
In SCD:
- 36/39 (92.3%) evaluable patients (with at least 16 months of follow-up) were free from vaso-occlusive crises (VOCs) for at least 12 consecutive months (VF12), consistent with previously reported primary endpoint data. The mean duration of VOC-free was 27.9 months, with a maximum of 54.8 months.
- 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 previously reported key secondary endpoint data.
In TDT:
- 49/52 (94.2%) evaluable patients (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 previously reported primary endpoint data. The mean duration of transfusion independence was 31.0 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. Edited levels of BCL11A alleles were stable over time in bone marrow and peripheral blood, indicating successful long-term hematopoietic stem cell editing. The safety profile of exa-cel was generally consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant.
Presentations at EHA Congress:
- Abstracts S273 and S274 (oral presentations): “Exagamglogene Autotemcel For Severe Sickle Cell Disease” and “Exagamglogene Autotemcel For Transfusion-Dependent Beta-Thalassemia,” on Sunday, June 16.
- Abstracts P1493 and P1525 (poster presentations): “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 Beta-Thalassemia,” on Friday, June 14.
Vertex will also present five health economics abstracts at the EHA Congress, covering various aspects of treatment use, clinical outcomes, and complications in patients with SCD and TDT.
About CASGEVY™ (exagamglogene autotemcel [exa-cel]):
CASGEVY™ is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, editing the BCL11A gene to produce high levels of fetal hemoglobin (HbF). CASGEVY has shown to reduce or eliminate VOCs for SCD patients and transfusion requirements for TDT patients. It is approved for certain indications in multiple jurisdictions for eligible patients.
