Reni-Cel Displays Clinical Benefit for Transfusion-dependent Beta Thalassemia

Haydar Frangoul, MD, MS

Credit: Twitter

The latest safety and efficacy data from the Phase 1/2 EdiTHAL clinical trial demonstrate the promising effect of renizgamglogene autogedtemcel (reni-cel), formerly known as EDIT-301, in the treatment of transfusion-dependent beta-thalassemia (TDT).¹

Announced by Editas Medicine, Inc. on June 14, 2024, reni-cel was well-tolerated and demonstrated an early and robust increase of total hemoglobin and fetal hemoglobin (HbF) without transfusions for up to 12.8 months in EdiTHAL.

These data were presented in a poster presentation at the European Hematology Association (EHA) Hybrid Congress in Madrid, Spain.

“The preliminary safety and efficacy results from the EdiTHAL trial demonstrate this investigational medicine has been well-tolerated and shows promising efficacy for patients,” said Haydar Frangoul, MD, MS, medical director of pediatric hematology and oncology at the Sarah Cannon Research Institute and HCA Healthcare’s TriStar Centennial Children’s Hospital.¹ “Reni-cel has the potential to be a functional cure for people living with transfusion-dependent beta thalassemia, and we look forward to continuing to evaluate its effectiveness for these patients.”

Reni-cel is the first investigational AsCas12a gene-edited cell therapy medicine being studied in EdiTHAL as a potential one-time, durable therapy.² EdiTHAL is a single-arm, open label, multi-center Phase 1/2 study designed to assess the safety and efficacy of reni-cel for 7 people living with TDT.

The medicine consists of patient-derived CD34+ hematopoietic stem and progenitor cells edited at the gamma-globin gene (HBG1 and HBG2) promoters. Red blood cells from reni-cel CD34+ cells demonstrate increased fetal hemoglobin (HbF) production, which can have a durable treatment effect in patients with TDT.

Upon analysis, patients with TDT experienced early and robust increases in total hemoglobin and HbF, with total hemoglobin rising above the transfusion independence threshold of 9.0 g/dL.

For those with ≥6 months follow-up (n = 6), the mean total hemoglobin and HbF concentrations at 6 months were 12.1 g/dL and 10.9 g/dL, respectively. These levels were sustained at or above the 6-month transfusion threshold across later follow-up periods.

All patients remained transfusion-free for 4.1 to 12.8 months after receiving the last red blood cell transfusion at 0.5 – 2.2 months post-reni-cel infusion. In addition, all patients exhibited high levels of editing in the HBG1 and HBG2 promoter regions.

Safety data revealed the promising profile of reni-cell, demonstrating consistent tolerance to myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant in all patients in EdiTHAL. After infusion, all patients had successful neutrophil and platelet engraftment, at a median of 23 and 38 days, respectively.

There were no serious adverse events related to reni-cel treatment reported in EdiTHAL.

In a statement, Baisong Mei, MD, PhD, chief medical officer at Editas Medicine, indicated the company continues to progress significantly in developing reni-cel for TDT.¹ All patients demonstrated early increases in HbF, maintained hemoglobin above the transfusion thresholds, and remained free from red blood cell transfusions after reni-cel infusion.

“These data further support our belief that reni-cel has the potential to be a clinically differentiated, one-time, durable medicine that can provide life-changing clinical benefits to patients,” Mei added.¹ “I would like to thank the participants, their families and caregivers, clinicians, and colleagues at collaborating institutions that contribute to the EdiTHAL trial.”

References

1. _{Editas Medicine, Inc. Editas Medicine announces new safety and efficacy data from the EDITHAL trial of Reni-cel in 7 patients with transfusion-dependent beta thalassemia, presented at the European Hematology Association (EHA) Annual Congress. GlobeNewswire News Room. June 14, 2024. Accessed June 14, 2024. https://www.globenewswire.com/news-release/2024/06/14/2898788/0/en/Editas-Medicine-Announces-New-Safety-and-Efficacy-Data-from-the-EdiTHAL-Trial-of-Reni-cel-in-7-Patients-with-Transfusion-dependent-Beta-Thalassemia-Presented-at-the-European-Hemato.html.}
2. _{Editas medicine to present clinical data from the ruby and Edithal Trials of reni-CEL at the European Hematology Association 2024 Congress in June. Editas Medicine. May 14, 2024. Accessed June 14, 2024. https://ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-present-clinical-data-ruby-and-edithal-trials-0.}
3. _{Farmakis D, Porter J, Taher A, Domenica Cappellini M, Angastiniotis M, Eleftheriou A. 2021 Thalassaemia International Federation Guidelines for the Management of Transfusion-dependent Thalassemia. Hemasphere. 2022;6(8):e732. Published 2022 Jul 29. doi:10.1097/HS9.0000000000000732}