Editas Medicine Announces New Safety and Efficacy Data from RUBY Trial in Sickle Cell Disease at EHA Congress

Editas Medicine, Inc., a clinical-stage genome editing company, has announced promising new safety and efficacy data from a Phase 1/2/3 clinical trial involving 18 patients with severe sickle cell disease (SCD). This trial, named RUBY, is evaluating renizgamglogene autogedtemcel (reni-cel), an investigational gene-edited cell therapy. The findings will be presented on June 15, 2024, at the European Hematology Association (EHA) Hybrid Congress in Madrid, Spain.

Reni-cel, the first investigational AsCas12a gene-edited cell therapy, is being explored as a one-time, durable treatment option for severe SCD patients. All 18 patients in the RUBY trial tolerated the treatment well. Importantly, they experienced no vaso-occlusive events (VOEs) for up to 22.8 months following the infusion of reni-cel. Total hemoglobin levels normalized early, with the mean hemoglobin within the normal range above 14 g/dL. Additionally, there were rapid and sustained improvements in fetal hemoglobin (HbF), with levels exceeding 40%.

Patients in the RUBY trial underwent a median of two apheresis and mobilization cycles. The observations from this trial indicate that reni-cel has the potential to be a transformative and durable medicine, providing significant clinical benefits to SCD patients. Dr. Baisong Mei, Chief Medical Officer of Editas Medicine, emphasized the promising nature of these results and the substantial progress in the development of reni-cel. The trial has now dosed over 20 patients, completed adult cohort enrollment, and started enrolling adolescent patients.

Dr. Rabi Hanna, the presenting investigator and Chairman of the Division of Pediatric Hematology Oncology and Blood and Marrow Transplantation at Cleveland Clinic Children’s, expressed optimism about the trial results. He highlighted that reni-cel has shown a favorable safety profile and promising efficacy, warranting further investigation as a gene-edited therapy for SCD.

Key efficacy data from the RUBY trial include:
- All 18 patients had no VOEs post-reni-cel infusion, with follow-up durations ranging from 2.4 to 22.8 months.
- At six months of follow-up, the mean total hemoglobin was 14.3 g/dL, and the mean fetal hemoglobin was 48.5%.
- Fetal hemoglobin-containing red cells (F-cells) were sustained above 90% from month four onwards.
- Mean corpuscular fetal hemoglobin (MCH-F) levels remained above 10 pg/F-cell by month three, indicating strong anti-sickling activity.
- High levels of genetic editing in the HBG1 and HBG2 promoter regions were sustained in all patients.
- Markers of hemolysis were either normalized or improved.

Regarding safety, reni-cel demonstrated a favorable profile. All patients showed successful neutrophil and platelet engraftment, with a median of 23 and 24 days for neutrophil and platelet engraftment, respectively. No serious adverse events related to reni-cel treatment were reported among the patients.

Additionally, Editas Medicine will present data from the EdiTHAL trial, which is investigating reni-cel for transfusion-dependent beta thalassemia, in a poster presentation at the EHA.

Reni-cel, formerly known as EDIT-301, is a gene-editing treatment under investigation for severe SCD and transfusion-dependent beta thalassemia (TDT). It involves editing patient-derived CD34+ hematopoietic stem cells at the gamma globin gene promoters using AsCas12a. This approach aims to provide sustained increases in fetal hemoglobin production, potentially offering a long-lasting therapeutic benefit for patients.

The RUBY trial is a comprehensive study designed to evaluate the safety and efficacy of reni-cel in severe SCD patients, marking the first clinical use of AsCas12a for human cell editing. Meanwhile, the EdiTHAL trial is assessing reni-cel's safety and efficacy in patients with TDT.

Editas Medicine, as a clinical-stage gene editing company, is dedicated to developing treatments for severe diseases using CRISPR/Cas12a and CRISPR/Cas9 genome editing technologies. The company holds exclusive licenses for these technologies from Broad Institute and Harvard University.