EDIT-301 Increases Total and Fetal Hemoglobin in Patents with Sickle Cell Disease


The therapy seems to have a similar benefit in the first patient with TDT in the EdiTHAL trial.

EDIT-301, an AsCas12a-edited cell therapy, was well-tolerated and restored total and fetal hemoglobin (HbF) in patients with sickle cell disease (SCD) in the phase 1/2 RUBY trial (NCT04853576), with a trend of similar benefit seen in the first patient with transfusion-dependent β-thalassemia (TDT) in the phase 1/2 EdiTHAL trial (NCT05444894).1

Data from the RUBY trial were presented at the European Hematology Association (EHA) 2023 Congress, held June 8-11, both virtually and in Frankfurt, Germany, by Rabi Hanna, MD, chairman, department of pediatric hematology-oncology and bone marrow transplantation, Cleveland Clinic Children's, Cleveland Clinic.

“These promising data support our belief that EDIT-301 can be a clinically differentiated, one-time, durable medicine that can provide life changing clinical benefits to patients with sickle cell disease and beta thalassemia long term, specifically driving early and robust correction of anemia and sustained increases in fetal hemoglobin,” Baisong Mei, MD, PhD, senior vice president and chief medical officer, Editas Medicine, said in a statement.2 “I would like to thank the clinical trial participants, their families, clinicians, and colleagues at collaborating institutions that contribute to the RUBY and EdiTHAL trials. We remain on-track to dose 20 RUBY patients by year-end, and we look forward to sharing further RUBY and EdiTHAL clinical updates later this year.”

READ MORE: FDA Accepts Exa-cel BLA for Sickle Cell and Transfusion-Dependent β-Thalassemia

Four participants received a single infusion of EDIT-301 (≥3 × 10 6 CD34 + cells/kg) after myeloablative conditioning with busulfan in the RUBY trial. Investigatorts monitored participants for engraftment, total hemoglobin (Hb), HbF production, mean HbF concentration/Fcell (MCH-F/F-cell), percentage of F-cells, markers of hemolysis, transfusion requirement, VOEs, and adverse events (AEs) for 24 months.

Hanna and colleagues found that editing the cells with AsCas12a resulted in over an 80% editing rate in participants’ cells. As of May 2023, 2 patients were within 10 (patient 1) and 6 months (patient 2) post infusion. These 2 patients achieved neutrophil and platelet engraftment within 23 and 19 days (patient 1) and within 29 and 37 days (patient 2) of EDIT-301 infusion. At 5 months, patient 1 had total Hb at a normal physiological level of 16.4g/d which was maintained at 10 months and an HbF fraction increasing from 5% at baseline to 45.4% at 5 months and 43.4% at the 10-month follow-up. Patient 2 Hb reached a normal physiological level of 12.7 g/dL at 5 months and an HbF fraction increasing from 10.8% to 51.3% at 6 months from baseline. Patients 3 and 4, within 3 and 2 months of follow-up, are trending similarly to the first 2 patients and all 4 patients have been free of VOEs.

In the EdiTHAL trial, the first patient demonstrated successful neutrophil and platelet engraftment with a similar trend of response in the RUBY patients at 1.5 months post infusion. EDIT-301 had a safety profile consistent with myeloablative conditioning with busulfan, with no related or serious AEs after infusion in both RUBY and EdiTHAL.

“I am encouraged by the results from the RUBY trial, which indicate this investigational gene editing treatment has been well-tolerated and efficacious in treated trial participants thus far. While we need to let the trial finish and enroll many other patients to understand the overall benefits and risks of this treatment, I am pleased to see transformative results at this stage in the study,” Hanna added.2

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1. Hanna R, Frangoul H, Mckinney C, et al. 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. Presented at: EHA 2023 Congress; June 8-11; Frankfurt, Germany.
2. Editas Medicine announces positive initial EDIT-301 safety and efficacy data from the first four patients treated in the RUBY trial and the first patient treated in the EdiTHAL trial. News release. Editas Medicine. June 9, 2023. https://www.globenewswire.com/news-release/2023/06/09/2685321/0/en/Editas-Medicine-Announces-Positive-Initial-EDIT-301-Safety-and-Efficacy-Data-from-the-First-Four-Patients-Treated-in-the-RUBY-Trial-and-the-First-Patient-Treated-in-the-EdiTHAL-Tri.html
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