Genome-Edited Cell Therapy Reduces VOEs in Sickle Cell Disease


The first 2 participants dosed are free of vaso-occlusive events as of 5 and 1.5 months of follow-up after treatment with EDIT-301.

EDIT-301 (Editas Medicine) was well-tolerated and reduced vaso-occlusive events (VOEs) in the first 2 participants with severe sickle cell disease (SCD) treated in the first-in-human phase 1/2 RUBY trial (NCT04853576).

“These promising clinical results from the RUBY trial suggest clinical proof of concept for EDIT-301 and 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 severe sickle cell disease long term,” Baisong Mei, MD, PhD, senior vice president and chief medical officer, Editas Medicine, said in a statement.1 “I would like to thank the participants, their families, clinicians, and colleagues at collaborating institutions that contribute to the RUBY trial. We look forward to sharing further clinical updates in mid-2023.”

Both participants achieved successful neutrophil and platelet engraftment, patient 1 at 23 and 19 days after EDIT-301 infusion, respectively, and patient 2 at 29 and 37 days after infusion, respectively. At 5- and 1.5-months follow-up after treatment, neither patient has experienced any VOEs. At this time, the first patient had a total hemoglobin of 16.4 g/dL, a fetal hemoglobin (HbF) of 45.4%, and a mean corpuscular HbF of 13.8 pg/red blood cell (enough to suppress sickling). TheHbF increase was also highly pancellular, and F cells steadily increased to reach greater than 95% of red blood cells.

EDIT-301 was well-tolerated, with a safety profile consistent with busulfan myeloablative conditioning and autologous hematopoietic stem cell transplant. Investigators did not observed any serious adverse events (AEs) or any AEs related to treatment with EDIT-301.

READ MORE: Base-Editing HSC Therapy Enrolls First Patient With Sickle Cell Disease

EDIT-301 consists of autologous CD34+ hematopoietic stem and progenitor cells edited with the proprietary, specific, and efficient AsCas12a gene editing nuclease at the gamma globin gene (HBG1 and HBG2) promoters to increase expression of HbF, mimicking a natural mechanism of hereditary persistence. It is also being investigated in transfusion-dependent beta thalassemia (TDT) in the EDITHAL trial (NCT05444894), which is dosing its first patient this year.

The RUBY trial’s primary end point will measure the post-treatment rate of severe VOEs requiring medical attention compared to pre-treatment. Secondary end points will include the proportion of patients with mean HbF greater than 20% compared to baseline, and the proportion of patients with mean Hb greater than or equal to 10 g/dL 60 days or more after the last packed red blood cell transfusion compared to baseline. The change from baseline in annualized rate of hospitalization for severe VOE will also be evaluated.A clinical hold on RUBY, relating to the need for an improved potency assay before collection of efficacy data for a marketing application could begin, was lifted in July 2022, when Editas also revealed that the first participant had been treated.

“It is an exciting time at Editas as we continue to build momentum for our EDIT-301 program,” Gilmore O’Neill, MB, MMSc, president and chief executive officer, Editas Medicine, said in a statement at that time.2 “Dosing and successful engraftment of the first patient coupled with the FDA’s removal of the partial clinical hold on the RUBY trial are important steps toward our goal of bringing this new and promising treatment to people living with SCD and thalassemia.”

1. Editas Medicine announces positive safety and efficacy data from the first two patients treated in the RUBY trial Of EDIT-301 for the treatment of severe sickle cell disease. News release. Editas Medicine. December 6, 2022.
2. Editas Medicine announces clinical achievements in the development of EDIT-301 for sickle cell disease. News release. Editas Medicine, Inc. July 27, 2022.
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