Editas' Gene Therapy Trial for Sickle Cell Initiates After Hold Lifted


The company announced successful neutrophil and platelet engraftment for the first patient dosed.

The FDA has removed a partial clinical hold on Editas Medicine’s phase 1/2 clinical trial of experimental cell therapy EDIT-301 for the treatment of severe sickle cell disease (SCD; RUBY; NCT04853576) and the first patient in the trial has been dosed.1 

The hold was related to the need for an improved potency assay before collection of efficacy data for a marketing application could begin.2 The company announced that neutrophil and platelet engraftment for the first patient dosed was successful.1 It was also the first time that Editas Medicine’s proprietary AsCas12a enzyme, a gene editing nuclease, had been used to edit human cells in a clinical trial.

“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.1 “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.”

EDIT-301 consists of autologous CD34+ hematopoietic stem cells edited at the HBG1 and HBG2 gamma globin promoter genes. Red blood cells derived from EDIT-301 CD34+ have shown evidence of increased fetal hemoglobin (HbF) production, which is expected to inhibit the polymerization of the sickle hemoglobin protein (HbS) that drives the disease.

The single-arm, multicenter study will aim to enroll 40 participants across multiple sites in the US and Canada. These participants must be between the ages of 18 to 50 years and diagnosed with severe SCD, defined by a documented severe genotype and at least 2 severe vaso-occlusive crisis events per year that require medical attention despite supportive care measures. Patients with contraindications to autologous hematopoietic stem cell transplant (HSCT), a history of severe cerebral vasculopathy, and those who have advanced liver disease, immunodeficiency disorders, or clinically significant and active infections will be excluded from the study.

Patients will be administered EDIT-301 as a one-time intravenous infusion after myeloablative conditioning with busulfan. The primary end point will measure the post-treatment rate of severe vaso-occlusive events (VOE) 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. The trial is in the process of enrolling additional participants and top-line clinical data is expected to be announced by the end of 2022.

EDIT-301 is also going to be investigated for the treatment of transfusion-dependent beta thalassemia (TDT) in a separate clinical trial (EDITHAL; NCT05444894). The single-arm, multicenter phase 1/2 study will seek to enroll 6 participants aged 18 to 35 with diagnosed TDT. Primary end points will include the proportion of participants achieving neutrophil engraftment and the frequency and severity of adverse events. Secondary end points will include the incidence of transplant related mortality and all-cause mortality, and the proportions of participants with the intended genetic modification present in both peripheral blood and bone marrow over time. The first patient with TDT is expected to be dosed in the clinical trial this year.

1. Editas Medicine announces clinical achievements in the development of EDIT-301 for sickle cell disease. News release. Editas Medicine, Inc. July 27, 2022. https://ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-announces-clinical-achievements-development-edit 
2. Editas Medicine announces the FDA has cleared initiation of the EDIT-301 clinical trial. News release. Editas Medicine, Inc. January 11, 2021. https://ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-announces-fda-has-cleared-initiation-edit-301

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