CRISPR gene therapy using the Cas12a enzyme is showing early promise in patients with severe sickle cell disease. The investigational therapy, renizgamglogene autogedtemcel, aims to reactivate fetal hemoglobin production by disrupting the BCL11A binding sites in the HBG1 and HBG2 promoters.
In a phase 1-2 open label study, 28 patients aged 12 to 50 years with severe sickle cell disease received a single infusion after myeloablative conditioning. All had experienced at least two severe vaso-occlusive events annually in the prior two years.
At a median follow-up of 9.5 months, 27 of 28 patients achieved neutrophil and platelet engraftment. Among 18 patients with at least six months of data, mean total hemoglobin rose from 9.8 g/dL at baseline to 13.8 g/dL. Fetal hemoglobin increased from 2.5% to 48.1% by month six.
Only one patient experienced two severe vaso-occlusive events after infusion; the remaining 27 reported none. Adverse events were consistent with those expected after busulfan conditioning and stem cell transplant. The study was terminated early after a reassessment of clinical development priorities, and the analysis was not prespecified. Nevertheless, the data support further investigation of this gene editing approach.