RUBY: Promising data for first AsCas12a gene-editing therapy in sickle cell disease

Renizgamglogene autogedtemcel (reni-cel) established a swift and durable normalisation in haemoglobin and improvements in haemolysis markers.

Mean Hb levels increased rapidly and were sustained

Reni-cel is a gene-edited stem cell therapy of CD34+ cells, edited at the γ-globin gene (HBG1 and HBG2) promoters. The idea is that these edits will lead to the production of foetal Hb, which is an important factor in reducing sickle cell disease. The phase 1/2 RUBY trial (NCT04853576) exposed 18 participants with severe sickle cell disease to a single infusion of reni-cel. Dr Rabi Hanna (Cleveland Clinic, OH, USA) shared findings from an interim analysis of this study1.

After a mean post-infusion follow-up of 6.2 months, none of the participants had experienced a vaso-occlusive event (VOE), compared to a mean of 5.2 severe VOEs per year in the 2 years before the reni-cel infusion. Moreover, mean Hb levels increased rapidly and were sustained at 14.4 g/dL from month 5. Dr Hanna added that the mean percentage of foetal Hb was 48.0% at month 4. Likewise, F-cells and mean HbF concentration/F-cell increased quickly and these changes were maintained over time. Key markers of haemolysis indicated improvement and/or normalisation in all participants who were treated with reni-cel. Finally, Dr Hanna explained that the safety profile of reni-cel was comparable with myeloablative conditioning with busulfan and that there were no adverse events directly related to reni-cel.

Reni-cel induced a swift and sustained normalisation of Hb, an early increase in foetal Hb, and improvements in key markers of haemolysis. Together with the VOE-free status of the participants after infusion and the favourable safety profile, the results suggest that this promising gene-editing therapy should be further investigated in larger cohorts of patients with sickle cell disease.

Medical writing support was provided by Robert van den Heuvel.

  1. Hanna R, et al. Reni-cel, the first AsCas12a gene-edited cell therapy, led to hemoglobin normalization and increased fetal hemoglobin in severe sickle cell disease patients in an interim analysis of the RUBY trial. Abstract #S285, EHA congress 2024, 13–16 June, Madrid, Spain.