Editas notches milestones for sickle cell disease therapy as FDA lifts partial clinical hold

Editas Medicine has confirmed that a cell therapy for sickle cell disease has successfully engrafted into the first patient dosed in a phase 1/2 trial, which means—for those of us without a science degree—the therapy has been accepted by the patient's body and is starting to create new blood cells as planned. 

The gene editing company also announced that a partial clinical hold on the efficacy portion of the RUBY trial for EDIT-301 has now been lifted. The FDA had asked Editas to come up with an improved potency assay to be developed after the first patients were dosed in the safety portion of the trial before proceeding with the efficacy side. The efficacy group is what Editas will use for registration, or to create a marketing application for approval of EDIT-301.

Editas created the potency assay as requested to meet the FDA requirements and the hold was lifted, according to spokeswoman Cristi Barnett. The company can now use efficacy data from patients in the RUBY trial for a future marketing application. 

Both events are key milestones as Editas looks ahead to an end-of-year readout for EDIT-301, which is being tested in patients with severe sickle cell disease, according to CEO Gilmore O’Neill. While Editas has had an early readout for another therapy, EDIT-101 in the eye disorder Leber congenital amaurosis 10, this marks the first time that Editas’ proprietary gene editing nuclease, or engineered AsCas12a enzyme, has been used to edit human cells in a clinical trial.

The main goal of RUBY is safety, specifically the rate of severe vaso-occlusive events requiring medical attention. This complication occurs in patients with sickle cell disease when the sickle-shaped cells block blood flow to tissues and deprive them of oxygen. The secondary efficacy measures will look at reductions in fetal hemoglobin, which is a key biomarker in sickle cell disease, required blood transfusion during the trial and other outcomes.

Editas said dosing has occurred in the EDIT-301 trial and successful neutrophil and platelet engraftment has been confirmed—an important signal that suggests the therapy is working. The cell therapy consists of patient-derived CD34+ hematopoietic stem and progenitor cells that have been edited at the gamma globin gene promoters. This is where fetal hemoglobin mutations reside. Editas is hoping that red blood cells derived from EDIT-301 will have a sustained increase in fetal hemoglobin production, providing a one-time treatment option for patients with the chronic disease. Patients in RUBY will receive a single dose. 

EDIT-301 is also being investigated in transfusion-dependent beta thalassemia. Editas is currently prepping that phase 1/2 study, called EDITHAL, for initiation. Dosing is expected to kick off in 2022.

Editas just brought on a new chief medical officer, Baisong Mei, M.D., Ph.D., from Sanofi, who will oversee clinical development of EDIT-301. He previously oversaw hemophilia, sickle cell disease and beta thalassemia treatments.

Sickle cell and beta thalassemia have become a competitive therapeutic area as cell therapies become more common. Bluebird bio is moving lovo-cel toward an FDA filing in sickle cell disease, while beti-cel is already before the regulators for beta thalassemia. Vertex and CRISPR Therapeutics also have a partnership to work on the diseases.