The new data on the long-term use of exa-cel (exagamglogene autotemcel), a non-viral cell therapy, with ex vivo genetic modification Crispr/Cas9, coming from global clinical studies on people suffering from severe sickle cell anemia (Scd) or transfusion-dependent beta-thalassemia (Tdt). The results, presented at the recent Annual Congress of the European Hematology Association (EHA) – and released by Vertex Pharmaceuticals Incorporated – confirm the potentially transformative and long-lasting clinical benefits of exa-cel, the first and only approved gene editing-based therapy on Crispr/Cas9 technology.
The data presented – we read in a note – refer to more than 100 patients (46 Scd; 56 Tdt) treated with exa-cel during clinical trials, the longest follow-up of which extends to more than 5 years. The efficacy results are consistent with previously reported primary and secondary endpoint analyzes from these exa-cel studies and continue to demonstrate potentially transformative clinical benefit with durable and stable fetal hemoglobin (HbF) levels and allelic editing.
“The potentially transformative benefit seen in sickle cell disease patients throughout the study is impressive, considering the significant and cumulative disease burden that people with this blood disease face,” said Haydar Frangoul, medical director of Hematology and Pediatric Oncology at HCA Healthcare’s Sarah Cannon Research Institute and TriStar Centennial Children’s Hospital – I am eager to offer this therapy and the opportunity for a potential functional cure to my eligible patients.” The data presented “relating to adult and adolescent patients with TDT – stated Franco Locatelli, professor of Paediatrics at the Catholic University of the Sacred Heart of Rome, director of the Department of Pediatric Hematology and Oncology of the Bambino Gesù Pediatric Hospital – are added to the growing body of evidence in favor of exa-cel, confirming the importance of ensuring the availability of this innovative treatment to eligible patients as soon as possible. With the longest follow-up, which has now reached more than 5 years and demonstrating levels stable total and fetal hemoglobin, there is now evidence of a lasting benefit from exa-cel for patients to whom the treatment has been administered.”
In detail, the presentations – 2 oral presentations and 2 posters – include updated data from the pivotal studies of patients treated with exa-cel in Climb-111 and Climb-121 and followed in Climb-131.
New data from the pivotal exa-cel study highlights that 36 of 39 patients (92.3%) with SCD and evaluable (those with at least 16 months of follow-up) were free from vaso-occlusive crises (VOC) for at least 12 months consecutive (Vf12), consistent with previously reported primary endpoint data. The average duration of absence of Voc was 27.9 months, with a maximum of 54.8 months. In TDT, 49 of 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 weighted mean hemoglobin of at least 9 g/dL (Ti12 ), consistent with previously reported primary endpoint data. The average duration of transfusion independence was 31.0 months, with a maximum of 59.4 months. All dosed TDT patients with at least 16 months of follow-up are transfusion-free, and 2 of the 3 patients who did not achieve Ti12 in Climb-111 achieved Ti12 in the long-term follow-up study, Climb-111. 131, and have been independent of transfusions for over a year. The third has been free of transfusions for 3.4 months. Both SCD and TDT patients reported long-lasting, clinically significant improvements in quality of life, including physical, emotional, social/family, and functional well-being, as well as general health status.
Furthermore, in both Scd and Tdt patients, levels of edited Bcl11A alleles remained stable over time in bone marrow and peripheral blood, indicating successful editing in hematopoietic stem cells in the long term. All patients achieved neutrophil and platelet engraftment after exa-cel infusion. The safety profile of exa-cel – concludes the note – was generally consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplantation.
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