Reni-Cel Demonstrates Promising Results in SCD

Renizgamglogene autogedtemcel (reni-cel) led to hemoglobin (Hb) normalization and increased fetal hemoglobin (HbF) in patients with sickle cell disease (SCD), according to the phase I/II/III RUBY trial. The results were presented by Mark Walters, MD, of the University of California, San Francisco Benioff Children’s Hospital, at the 2025 Tandem Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR.

The multicenter, open-label, single-arm trial included 21 patients aged 12 to 50 years with severe SCD, defined as having at least two severe vaso-occlusive events (VOEs) per year in the two years before trial enrollment. Patients had an average of 4.9 severe VOEs per year during this interval.

After myeloablative conditioning with busulfan, patients were given a single infusion of reni-cel (≥3 × 10⁶ CD34+ cells/kg) and monitored for two years. The median number of days to neutrophil engraftment was 23.0, and the median number of days to platelet engraftment was 24.5. At six months, the mean total Hb was 14.2 g/dL, and the mean HbF was 48.2%. The mean HbF concentration per F-cell  remained above 10 pg/F-cell through the last follow-up, and the researchers observed improved or normalized hemolysis markers by six months.

Dr. Walters and colleagues also noted high levels of allelic editing at one year. The mean percentage of edited alleles in peripheral blood nucleated cells was 80.9%, and the mean percentage of edited alleles in bone marrow–derived CD34+ cells was 86.9%.

In terms of safety, no patients experienced VOEs after reni-cel infusion.

“Results with reni-cel treatment were promising, including reliable and prompt engraftment, early Hb normalization, and durable increases in HbF. The data also demonstrate improvement in hemolysis markers, sustained high levels of editing, resolution of VOEs, and a safety profile consistent with myeloablative conditioning with busulfan,” Dr. Walters and colleagues concluded.

Reference

Walters M, Frangoul H, McKinney C, et al. Reni-cel, an investigational AsCas12a gene-edited cell medicine, led to sustained hemoglobin normalization and increased fetal hemoglobin in patients with severe sickle cell disease treated in the RUBY trial. Abstract #719. Presented at the 2025 Tandem Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 12-15, 2025; Honolulu, Hawai’i.