RUBY: Reni-Cel Displays Promising Efficacy, Safety for Sickle Cell Disease

Rabi Hanna, MD

Credit: Cleveland Clinic

All patients with sickle cell disease (SCD) treated with renizgamglogene autogedtemcel (reni-cel), formerly known as EDIT-301, in the Phase 1/2/3 RUBY clinical trial remained free of vaso-occlusive events (VOEs) post-infusion.¹

Announced by Editas Medicine, Inc. on June 14, 2024, reni-cel is the first investigational AsCas12a gene-edited cell therapy medicine being studied in RUBY as a potential one-time, durable therapy for severe SCD.

The data will be discussed in an oral presentation at the European Hematology Association (EHA) Hybrid Congress in Madrid, Spain.

“I am encouraged by these results from the RUBY trial, demonstrating this investigational gene editing medicine has been well-tolerated and shows promising efficacy for people living with sickle cell disease,” said presenting investigator Rabi Hanna, MD, chairman of the division of pediatric hematology oncology and blood and marrow transplantation at Cleveland Clinic Children’s.¹

Reni-cell is an experimental gene editing medicine under investigation for treating SCD and transfusion-dependent beta-thalassemia (TDT).² The medicine consists of patient-derived CD34+ hematopoietic stem and progenitor cells edited at the gamma-globin gene (HBG1 and HBG2) promoters.

Red blood cells derived from reni-cel CD34+ cells show a sustained increase in fetal hemoglobin (HbF) production, with the potential for a one-time durable treatment effect in SCD and TDT.³ RUBY is a single-arm, open-label, multi-center Phase 1/2/3 study seeking to assess the safety and efficacy of reni-cel in 18 patients with severe SCD.

In RUBY, reni-cel remained well-tolerated and exhibited a safety profile consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant in all patients. After reni-cel infusion, patients remained free of VOEs for up to 23 months of follow-up, with follow-up ranging from 2.4 to 22.8 months.

Patients demonstrated early normalization of total hemoglobin with a mean within the normal range at >14 g/dL and rapid and sustained benefit in HbF with levels at >40%. Among those with ≥6 months follow-up, the mean total hemoglobin was 14.3 g/dL (n = 9) with a mean HbF of 48.5% (n = 10).

The mean percentage of F-cells increased early and sustained at >90% from month 4 through subsequent follow-ups from all patients with ≥4 months follow-up.

Notably, the mean corpuscular fetal hemoglobin (MCH-F) of HbF-containing red cells (F-cells) was sustained above the anti-sickling threshold of 10 pg/F-cell by month 3 after rein-cel infusion for all patients with ≥3 months follow-up.

All patients in RUBY showed sustained high levels of editing in the HBG1 and HBG2 promoter regions. Hemolysis markers were normalized or improved in patients treated with rein-cel.

Overall, reni-cel was well-tolerated and had a safety profile consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant in all RUBY participants. After infusion, all patients exhibited successful neutrophil (median, 23 days) and platelet engraftment (median, 24 days).

There were no serious adverse events considered related to reni-cel treatment in the RUBY trial.

Baisong Mei, MD, PhD, chief medical officer of Editas Medicine, indicated progress has been made in the RUBY trial, with more than 20 patients dosed with reni-cell, with complete adult enrollment and opened enrollment in the adolescent cohort.

“These data confirm the observations from our prior clinical readouts and further support our belief that reni-cel has the potential to be a best-in-class and clinically differentiated, one-time, durable medicine that can provide life-changing clinical benefits to patients,” Mei added.

References

1. _{Editas Medicine, Inc. Editas medicine reports new safety and efficacy data from the ruby trial of Reni-CEL in 18 patients with sickle cell disease, presented at the European Hematology Association (EHA) Annual Congress. GlobeNewswire News Room. June 14, 2024. Accessed June 14, 2024. https://www.globenewswire.com/news-release/2024/06/14/2898790/0/en/Editas-Medicine-Reports-New-Safety-and-Efficacy-Data-from-the-RUBY-Trial-of-Reni-cel-in-18-Patients-with-Sickle-Cell-Disease-Presented-at-the-European-Hematology-Association-EHA-An.html.}
2. _{Editas medicine to present clinical data from the ruby and Edithal Trials of reni-CEL at the European Hematology Association 2024 Congress in June. Editas Medicine. May 14, 2024. Accessed June 14, 2024. https://ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-present-clinical-data-ruby-and-edithal-trials-0.}
3. _{Elendu C, Amaechi DC, Alakwe-Ojimba CE, et al. Understanding Sickle cell disease: Causes, symptoms, and treatment options. Medicine (Baltimore). 2023;102(38):e35237. doi:10.1097/MD.0000000000035237}