Final Patient With TD β-thalassemia Dosed in Gene-edited Cell Therapy Trial


The study has now dosed 8 patients in total.

The final patient has completed dosing in the multicenter phase 1 clinical trial (NCT04925206) of EdiGene’s ET-01, an investigational autologous CRISPR-Cas9 Modified CD34+ human hematopoietic stem and progenitor cell product intended to treat transfusion dependent β-thalassemia (TDT).1

ET-01 features a CRISPR/Cas9-modified erythroid-specific enhancer of the BCL11A gene. The investigational new drug (IND) application for the trial was cleared by the China National Medical Products Administration’s Center for Drug Evaluation in January of 2021 and the first patient was enrolled in September of the same year.2 The study has now dosed 8 patients in total.

“The dosing of the 8th and last patient in our multi-center phase 1 study is another important milestone in our efforts to bring a potentially 1-time cure for patients with TDT,” Dong Wei, PhD, chief executive officer, EdiGene, said in a statement regarding the news.1 “We are deeply grateful for the patients and their families, as well as investigators whose participation and dedication have played a critical role in advancing the phase 1 study. The study outcome will shed important insight on the safety and efficacy profile of ET-01 in this particular patient population, and when at an appropriate time in 2023, we plan to discuss with regulators on phase 2 clinical study strategy and design, bringing ET-01 1 step closer to patients with TDT in China.”

The open-label, single-arm clinical trial was open to patients aged 12 years to 35 years who had been diagnosed with β-TDT. Participants were required to have a Lansky/Karnofsky score of at least 70% and to be eligible for hematopoietic stem cell transplantation and conditioning with busulfan in the investigator's judgement. Patients with associated α-thalassemia, any clinically significant acute or uncontrolled infections, a history of uncontrolled epilepsy or other mental disorders, or previous treatment with allogeneic bone marrow transplantation or gene therapy were excluded from participation. It was noted that other inclusion and exclusion criteria may apply.

Patients received intravenous ET-01 infusion after myeloablative conditioning with busulfan. The study’s primary end points are the frequency and severity of adverse events (AEs) and serious AEs, all-cause mortality, the incidence of transplant-related mortality, total lymphocyte count, and the proportion of patients with abnormal proliferation of blood cells. The trial includes locations in 3 cities in China and has an estimated completion date of June 30, 2024.

An earlier, single-patient clinical trial (NCT04390971) for ET-01 was initiated on August 11, 2020. The company plans to present preliminary data from that patient’s treatment at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, being held December 10-13, 2022 in New Orleans, Louisiana.3 The presentation will include data indicating that ET-01 treatment allowed for timely engraftment and significantly and durably raised production of fetal hemoglobin. EdiGene additionally noted that the patient was transfusion-independent from 3 months after administration of the treatment through 15 months to the May 20, 2022, data cut-off. In terms of safety, ET-01 here demonstrated a profile consistent with autologous hematopoietic stem cell transplantation and myeloablative conditioning.

“I am glad to see that the patient, who needed a transfusion of red blood cells every 2 weeks, has been transfusion free since February 2021,” Jun Shi, director, Regenerative Medicine Clinic at the Institute of Hematology and Blood Diseases Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College, and first presenter of the study, said in a statement earlier this month.3 “We are conducting additional research to further elucidate how gene-edited hematopoietic stem cells engraft and differentiate, hoping to shed light on the implication of gene editing in the short and long term.”

1. Edigene announces completion of last patient dosing in phase I clinical trial of ET-01, its investigational gene-editing hematopoietic stem cell therapy for transfusion dependent β-thalassemia. News release. EdiGene, Inc. November 18, 2022. 
2. Edigene announces approval of its IND application for its CRISPR/cas 9 gene-editing hematopoietic stem cell therapy ET-01 in β-thalassemia by China National Medical Products Administration. News release. EdiGene, Inc. January 18, 2021. 
3. Edigene to present preliminary safety and efficacy results of an investigator initiated trial for ET-01, its investigational gene editing hematopoietic stem cell therapy, at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition. News release. EdiGene, Inc. November 3, 2022. 
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