Reni-Cel Single Infusion Gene Editing Therapy Demonstrates Positive Results in Patients With Sickle Cell Disease

According to new clinical trial results, an experimental 1-time gene editing cell therapy, renizgamglogene autogedtemcel (reni-cel, formerly called EDIT-301), was well-tolerated in patients with sickle cell disease (SCD) and no serious adverse events (AEs) were observed. The findings were presented at the European Hematology Association (EHA) 2024 Hybrid Congress in Madrid, Spain.¹

The purpose of the open-label, single-arm, multicenter phase 1/2 clinical trial, RUBY (NCT04853576), is to evaluate the efficacy, safety, and tolerability of treatment with reni-cel, which is a treatment consisting of autologous gene edited CD34+ hematopoietic stem cells that corrects the mutation responsible for SCD, in adult and adolescent patients with severe SCD, which was defined as 2 or more severe vaso-occlusive events (VOEs) per year during the 2-year period prior to informed consent. A total of 18 patients aged 18 to 50 years were enrolled in the trial and received 1-time intravenous infusions of reni-cel following myeloablative conditioning with busulfan. The patients underwent a procedure where their stem cells were collected for gene editing, then received chemotherapy to clear any remaining bone marrow which makes room for the repaired cells later infused back into the body.^1-3

The primary end point for this trial was the proportion of patients achieving complete resolution of severe VOEs, which is measured up to 2 years following reni-cel infusion. Additionally, secondary end points included proportion of patients achieving complete resolution of VOEs, number of patients with 90% reduction in annualized rate of severe VOE compared to pre-treatment, the number of patients with 75% and 50% reduction in annualized rate of severe VOEs compared to pre-treatment, hospitalizations due to VOEs, changes from baseline in total hemoglobin (Hb) and HbF concentrations, among others, all of which were assessed up to 2 years following reni-cel infusion.²

According to the investigators, the patients enrolled tolerated reni-cel infusion without any serious AEs. Following treatment, patients had all successfully regained their white blood cells and platelets and were free of painful events since treatment. Further, those followed for 5 months or longer were observed to have their anemia resolved.¹

Earlier findings from March 2023 that detailed 4 patients who received reni-cel treatment were published in Hemasphere during August 2023. At this time, patients 1 and 2 were 8 and 4 months post-reni-cel infusion, respectively, and patients 3 and 4 were less than 1 month post-reni-cel infusion. Additionally, patients 1 was shown to achieve neutrophil and platelet engraftment within 23 and 19 days, respectively, of reni-cel treatment, and patient 2 within 29 and 37 days, respectively. Patient 1 had Hb increase from 4.5 g/dL from baseline to 16.4 g/dL at 6 months, and patient 2 had an increase from 3.6 g/dL at baseline to 12.1 g/dL at 3 months following reni-cel infusion. According to the investigators, all markers of hemolysis improved or normalized and editing levels in peripheral blood nucleated cells were mover 80% in both patients.³

Further, these 2 patients were also had no reported VOEs and demonstrated normal Hb concentrations and HbF levels of 35% or more. The safety profile of reni-cel was shown to be consistent with myeloablative conditioning with busulfan. The patients were also observed to have no AEs related to reni-cel, and no serious AEs following infusion.³

“It’s encouraging that this gene-editing treatment continues to show promising efficacy for sickle cell patients,” said the trial’s presenting investigator Rabi Hanna, MD, chairman of the division of pediatric hematology oncology and blood and marrow transplantation at Cleveland Clinic Children’s Hospital, in the news release. “These latest results offer hope that this new experimental treatment will continue to show progress and get us closer to a functional cure for this devastating disease.”¹

References

1. Cleveland Clinic. Novel gene-editing therapy continues to show positive results in sickle cell patients. News release. June 14, 2024. Accessed June 19, 2024. https://www.eurekalert.org/news-releases/1048381

2. A Study Evaluating the Safety and Efficacy of EDIT-301 in Participants With Severe Sickle Cell Disease (RUBY). ClinicalTrials.gov identifier: NCT04853576. Updated February 1, 2024. Accessed June 19, 2024. https://clinicaltrials.gov/study/NCT04853576

3. Hanna, R, Frangoul, H, Mckinney, C, et al. S264: EDIT-301 SHOWS PROMISING PRELIMINARY SAFETY AND EFFICACY RESULTS IN THE PHASE I/II CLINICAL TRIAL (RUBY) OF PATIENTS WITH SEVERE SICKLE CELL DISEASE USING HIGHLY SPECIFIC AND EFFICIENT ASCAS12A ENZYME. Hemasphere. 2023;7(Suppl ):e05170e0. Published 2023 Aug 8. doi:10.1097/01.HS9.0000967968.05170.e0