EHA 2023 | CLIMB Thal-111 & CLIMB SCD-121: TI and elimination of VOCs after exa-cel in TDT and SCD

In this presentation, Franco Locatelli, MD, IRCCS Bambino Gesu Children’s Hospital, Rome, Italy, discusses the CLIMB THAL-111 (NCT03655678) and CLIMB SCD-121 (NCT03745287) studies which have unveiled interim findings for exagamglogene autotemcel (exa-cel), a non-viral cell therapy, in patients with transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) respectively. Exa-cel utilizes ex vivo CRISPR/Cas9 gene-editing to reactivate the synthesis of fetal hemoglobin (HbF) by targeting the BCL11A gene in autologous CD34+ hematopoietic stem and progenitor cells. The primary endpoint of the CLIMB THAL-111 study was the proportion of patients achieving and maintaining over time an unsupported hemoglobin level greater than 9 g/dL without any transfusion support for at least 12 consecutive months. In the CLIMB SCD-121, the primary efficacy endpoint was the proportion of patients who have not experienced any severe vaso-occolusive crises (VOCs) for at least 12 consecutive months after exa-cel infusion. Among the 48 TDT patients who received exa-cel, 27 were evaluable for study endpoints at the pre-specified interim analysis, of whom 88.9% maintained a weighted average hemoglobin of ≥9 g/dL without transfusion for ≥12 months. Among the 17 patients with SCD evaluable for study endpoints, 94.1% met the primary endpoints of no severe VOCs ≥12 months. The trial also met the key secondary endpoints, with transfusion independence observed for 40.7 months in TDT and with VOC-free and no in-patient hospitalizations for VOCs for up to 36.5 months in SCD. In addition, the study reported early and sustained increases in HbF and total hemoglobin following exa-cel infusion. The safety profile of exa-cel was consistent with the myeloablative busulfan-based conditioning regimen and autologous transplantation procedures, with manageable adverse events. These results outline exa-cel’s potential as a one-time cure for patients with SCD and TDT by reaching transfusion independence and eliminating VOCs, improving hemoglobin levels, and quality of life. This press briefing took place at the European Hematology Association (EHA) Congress 2023, held in Frankfurt, Germany.

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