The FDA has asked Editas to come up with an improved efficacy test, which should be developed after the first patients are dosed in the safety part of the study before moving on to the efficacy side. (Dr_Microbe/iStock/Getty Images Plus)
Editas Medicine has confirmed that a sickle cell therapy has successfully taken root in the first patient dosed in a phase 1/2 study, which means—for those of us without a science degree—the therapy has been accepted by the patient’s body and is starting to make new blood cells according to plan.
The gene editing company also announced that the partial clinical efficacy suspension of the RUBY study for EDIT-301 has now been lifted. The FDA has asked Editas to come up with an improved efficacy test, which should be developed after the first patients are dosed in the safety part of the study before moving on to the efficacy side. The efficacy group is what Editas will use to register or create a marketing application for EDIT-301 approval.
Editas created the efficacy test on demand to meet the FDA’s requirements, and the suspension has been lifted, according to spokeswoman Cristi Barnett. The company can now use the efficacy data from patients in the RUBY study for a future marketing application.
Both events are key milestones as Editas expects year-end results for EDIT-301, which is being tested in patients with severe sickle cell disease, CEO Gilmore O’Neill said. While Editas had an early pipeline for another therapy, EDIT-101 for the eye disorder Leber congenital amaurosis 10, this is the first time that Editas’ proprietary gene-editing nuclease, or engineered enzyme AsCas12a, has been used to edit human cells in a clinical trial.
The main objective of RUBY is safety, specifically the rate of serious vaso-occlusive events requiring medical attention. This complication occurs in patients with sickle cell disease, when sickle cells block blood flow to tissues and deprive them of oxygen. Secondary measures of effectiveness will look at reductions in fetal hemoglobin, a key biomarker for sickle cell disease, the need for blood transfusions during the study and other outcomes.
Editas said dosing occurred in the EDIT-301 trial and confirmed successful engraftment of neutrophils and platelets — 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 engineered on gamma globin gene promoters.
This is where the fetal hemoglobin mutation resides. Editas hopes 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 chronic disease. Patients at RUBY receive one dose.
EDIT-301 is also being investigated in transfusion-dependent beta thalassemia. Editas is currently preparing a phase 1/2 study, called EDITHAL, to start. Dosing is expected to begin in 2022.
Editas has just hired a new Chief Medical Officer, Baisong Mei, M.D., Ph.D., from Sanofi, who will oversee the clinical development of EDIT-301. He previously oversaw the treatment of hemophilia, sickle cell disease and beta thalassemia.
Sickle cell disease and beta thalassemia have become competing therapeutic areas as cell therapies become more common. Bluebird bio moves lovo-cel toward FDA submission for sickle cell disease, while beti-cel is already ahead of regulators for beta thalassemia. Vertex and CRISPR Therapeutics are also collaborating on disease work.