RARE Daily

Editas Medicine Reports Positive Initial Data for Gene Editing Therapy for SCD and TDT

June 9, 2023

Rare Daily Staff

Editas Medicine reported positive initial safety and efficacy data from the first four patients with sickle cell disease treated with EDIT-301 in the RUBY trial and from the first transfusion-dependent beta thalassemia patient treated in the EdiTHAL trial.

Sickle cell disease (SCD) is an inherited blood disorder caused by a mutation in the beta-globin gene that leads to polymerization of the sickle hemoglobin protein (HbS). In sickle cell disease, the red blood cells are misshapen in a sickle shape instead of a typical disc shape. The abnormal shape causes the red blood cells to have shortened lifespan and to block blood flow causing anemia, pain crises, organ failure, and early death. Higher levels of fetal hemoglobin (HbF) inhibit HbS polymerization, thus reducing the clinical manifestation of RBCs sickling.

Beta thalassemia is an inherited blood disorder caused by mutations that reduce or abrogate beta globin gene expression. Insufficient beta globin production leads to ineffective red blood cell production, chronic hemolytic anemia, the creation of blood cells outside of the bone marrow, and requirement for regular blood transfusion support in patients with transfusion-dependent beta thalassemia (TDT). TDT is the most severe form of beta thalassemia, and chronic red blood cell transfusions are complicated by iron overload leading to organ dysfunction and failure. Higher levels of HbF ameliorate anemia thereby reducing the need for regular red blood cell transfusions.

EDIT-301 consists of patient-derived CD34+ hematopoietic stem and progenitor cells edited at the gamma globin gene (HBG1 and HBG2) promoters, where naturally occurring fetal hemoglobin (HbF) inducing mutations reside. Red blood cells derived from EDIT-301 CD34+ cells demonstrate a sustained increase in fetal hemoglobin production, which has the potential to provide a one-time, durable treatment benefit for people living with severe SCD and TDT.

The RUBY trial data will be presented in an oral presentation at European Hematology Association (EHA) Hybrid Congress in Frankfurt, Germany, and via live stream on Saturday, June 10.

In the RUBY trial, Patients 1 and 2 reached normal hemoglobin levels five months post-treatment with EDIT-301, and both patients have maintained a normal hemoglobin level at ten- and six-month follow-up, respectively. Additionally, each of these patients has seen fetal hemoglobin levels of greater than 40 percent persist during the same time frame. Patients 3 and 4 in the RUBY trial saw increases in total hemoglobin and fetal hemoglobin at three and two months of follow up, respectively, that follow similar trajectories as those seen in the first two patients. All four treated RUBY patients are also free of vaso-occlusive events since infusion.

In the EdiTHAL trial, the first patient demonstrated successful neutrophil and platelet engraftment, and, at one and a half months post-infusion, the patient’s response resembles that of the first four RUBY patients.

EDIT-301 was well-tolerated and demonstrated a safety profile consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant by the four patients in the RUBY trial and the first patient in the EdiTHAL trial. After EDIT-301 infusion, no serious adverse events occurred, and no adverse events reported were related to treatment with EDIT-301.

“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,” said Baisong Mei, senior vice president and chief medical officer of Editas Medicine.

Photo: Baisong Mei, senior vice president and chief medical officer of Editas Medicine.

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