New Gene Therapy May Lead to Increased Fetal Hemoglobin, Transfusion Independence in Patients With Bleeding Disorders

December 10, 2020

Two patients with inherited bleeding disorders who received an experimental gene therapy showed early, substantial, and sustained increases in fetal hemoglobin levels one year after receiving the treatment, according to preliminary results published recently in the New England Journal of Medicine. The experimental therapy, CTX001 (CRISPR Therapeutics and Vertex Pharmaceuticals), utilizes autologous CD34+ cells edited with CRISPR-Cas9 targeting the BCL11A erythroid-specific enhancer to reactivate the production of fetal hemoglobin. 

The findings describe clinical outcomes at 12 months for one patient with transfusion-dependent thalassemia, and a second patient with sickle cell disease, who each received a single intravenous infusion of CTX001. At the end of the follow-up period, both patients had high levels of allelic editing in bone marrow and blood, increases in fetal hemoglobin that were distributed pancellularly, and transfusion independence. The patient with sickle cell disease also experienced an elimination of vaso-occlusive episodes. According to the authors, the clinical course of both patients supports their conclusion that CTX001 mimics the phenotype of hereditary persistence of fetal hemoglobin levels.

Since the submission of their report, investigators administered CTX001 to an additional eight patients (six with thalassemia and two with sickle cell disease) and obtained follow-up data for more than 3 months. Initial efficacy data from these additional patients are broadly consistent with the findings in the two original patients described, but investigators noted that a fuller analysis of the use of CTX001 therapy in additional patients with longer follow-up will be needed to more extensively characterize the profile of this treatment.