Exa-Cel Shows Long-Term Clinical Benefit in Sickle Cell Disease, TDT


The CRISPR-based gene therapy demonstrated durable effects on SCD and TDT, with the longest follow-up extending past 5 years.

Exa-Cel Shows Long-Term Clinical Benefit in Sickle Cell Disease, TDT | Image Credit: Twitter

Haydar Frangoul, MD, MS

Credit: Twitter

Positive long-term data confirmed the consistent and durable benefit of exagamglogene autotemcel (exa-cel; CASGEVY™) in the treatment of severe sickle cell disease (SCD) or transfusion-dependent beta-thalassemia (TDT).1

Announced by Vertex Pharmaceuticals Incorporated on June 14, 2024, efficacy results in ≥100 patients treated with exa-cel remained consistent with primary and key secondary endpoints analyses from the CLIMB clinical trials, with the longest follow-up extending more than 5 years.

These data were presented at the Annual European Hematology Association (EHA) Congress in Madrid, Spain.

“The transformative benefit seen in patients with SCD in the trial is impressive given the significant and cumulative burden of disease faced by people living with this blood disorder,” said Haydar Frangoul, MD, MS, medical director of pediatric hematology and oncology at Sarah Cannon Research Institute and HCA Healthcare’s TriStar Centennial Children’s Hospital.1 “I am eager to offer this therapy and the opportunity of a potential functional cure to my eligible patients.”

Exa-cel is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible individuals with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited and high levels of fetal hemoglobin (HbF) are produced in red blood cells.2 It is the first and only approved CRISPR-based gene-editing therapy.

Across the CLIMB clinical trials, 46 patients with SCD and 56 patients with TDT were treated with exa-cel, with the longest follow-up of more than 5 years.1 These efficacy results continued to demonstrate transformative clinical benefits with durable and stable levels of HbF and allelic editing.

Among evaluable patients with SCD (n = 39), those with ≥16 months follow-up, 36 (92.3%) were free from vaso-occlusive crises (VOCs) for ≥12 consecutive months, remaining consistent with the primary endpoint data. The mean duration of VOC-free was 27.9 months and a maximum of 54.8 months.

Moreover, 38 (97.4%) patients with ≥16 months of follow-up were free from VOC-related hospitalizations for ≥12 consecutive months, remaining consistent with previously reported key secondary endpoint data.

Among evaluable patients with TDT (n = 52), those with ≥16 months of follow-up, 49 (94.2%) were transfusion-independent for ≥12 consecutive months with a mean weighted hemoglobin of ≥9 g/dL (TI12). These data were 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 patients with TDT dosed with exa-cel with ≥16 months of follow-up are transfusion-free.

Meanwhile, 2 of 3 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 patient has been transfusion-free for 3.4 months.

Both patients with SCD and TDT reported sustained and clinically meaningful improvements in quality of life, including physical, emotional, social/family, functional well-being, and overall health status, with exa-cel treatment.

Edited levels of BCL11A alleles were stable over time in bone marrow and peripheral blood showing successful editing in long-term hematopoietic stem cells in patients with SCD and TDT. All patients engrafted neutrophils and platelets after exa-cel infusion. Safety data remained consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant.

“The comprehensive data set present today for adult and adolescent TDT patients adds to the growing body of evidence of [exa-cel], 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, MD, PhD, a professor of pediatrics in the Catholic University of the Sacred Heart of Rome and the director of the department of pediatric hematology and oncology at Bambino Gesù Children’s Hospital.1 “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 [exa-cel].”


  1. Vertex presents positive long-term data on CASGEVYTM (exagamglogene autotemcel) at the 2024 annual European Hematology Association (EHA) Congress. Vertex Pharmaceuticals Newsroom. June 14, 2024. Accessed June 17, 2024. https://news.vrtx.com/news-releases/news-release-details/vertex-presents-positive-long-term-data-casgevytm-exagamglogene.
  2. Commissioner O of the. FDA approves first gene therapies to treat patients with sickle cell disease. U.S. Food and Drug Administration. December 8, 2023. Accessed June 17, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease.
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