Investigators from multiple institutions conducted a study to assess the efficacy and safety of Renizgamglogene autogedemcel (reni-cel) in the treatment of adolescents and adults with sickle cell disease. Reni-cel is an investigational, clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a, gene-edited autologous stem-cell therapy, designed to alter the BCL11a binding sites in the HBG1 and HBG2 promoters. HBG1 and HBG2 promote gamma-globin production, and BCL11A is a transcription factor that represses their function. The goal of the therapy is to promote production of fetal hemoglobin. Study participants were patients 12–50 years old with sickle cell disease and a history of ≥2 severe vaso-occlusive events per year in the previous 2 years who were enrolled at 24 sites in North America. For the treatment, autologous CD34+ hematopoietic stem and progenitor cells (HSPC) were collected by apheresis. Reni-cel was manufactured from the HSPCs with use of a engineered AsCas12a nuclease. After the patient underwent myeloablative conditioning, they received an infusion of reni-cel. The main study outcomes included neutrophil and platelet engraftment, hemoglobin levels after treatment, fetal hemoglobin percentage, occurrence of severe vaso-occlusive events, and adverse events. Although it was planned to enroll 45 participants, the sponsor terminated the study early because of changing priorities. Because of this, the analysis was limited to patients who received reni-cel before study termination.
