Haydar Frangoul, MD, Sarah Cannon Blood Cancer Center, Nashville, TN, discusses the results of two trials, CLIMB THAL-111 (NCT03655678) and CLIMB SCD-121 (NCT03745287), investigating the use of CTX001, a CRISPR-Cas9-edited CD34+ cellular therapeutic. It is believed that upregulation of fetal hemoglobin could reduce anemia and transfusion dependence in β-thalassemia and reduce common clinical complications such as vaso-occlusive crises in sickle cell disease (SCD). CD34+ hematopoietic stem and progenitor cells, collected from patients by apheresis, were edited using CRISPR technology to alter the erythroid enhancer region of BCL11A, a transcription factor which suppresses HbF production, to produce CTX001. In the CLIMB THAL-111 trial in patients with transfusion-dependent β-thalassemia, CTX001 treatment caused increases in total Hb and HbF, allowing transfusion independence shortly after CTX001 infusion. Three SCD patients were enrolled in the CLIMB SCD-121 trial and have experienced no vaso-occlusive crises since infusion. CTX001 treatment has proven tolerable and this early promising data suggests that CTX001 could be a beneficial therapy for β-thalassemia and SCD patients. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020
Haydar Frangoul, MD, is a steering committee member at Vertex Pharmaceutical.