Editas Medicine on Thursday said it will stop enrolling new patients in a clinical trial of its most advanced gene editing therapy and search for a partner to continue development of the CRISPR-based treatment.
The change in plans is in response to weaker-than-anticipated results from the trial, which tested Editas’ treatment in 14 patients with a genetic form for blindness, and represent another setback for a company that’s struggled with research delays and executive turnover. Shares fell by more than 15% Thursday morning.
Only three of the 14 study participants met Editas’ criteria for a positive response to treatment, called EDIT-101, while data for the others showed an inconsistent or negligible effect.
“While we will not progress EDIT-101 on our own and have made the decision to pause enrollment, we have the patient community top of mind and are looking for a collaboration partner to advance this program,” said Editas CEO Gilmore O’Neill in the company’s statement Thursday.
Despite its decision, Editas claims the data do support the company’s overall approach. “This is proof of concept that AAV-delivered CRISPR to the retina can actually drive a clinically meaningful response,” O’Neill said in an interview on Thursday morning.
Editas was one of several biotechnology companies formed following Nobel Prize-winning research that established CRISPR as a powerful tool for editing genes. EDIT-101, the company’s lead experimental therapy, was the first medicine based on CRISPR to be used to fix broken genes inside a person’s body, rather than on a patient’s cells modified in a laboratory.
But after reaching that landmark with the start of its trial in July 2019, Editas ran into delays enrolling patients in the study, a process complicated in part by the pandemic’s onset. AbbVie, which inherited a research collaboration with Editas through its acquisition of Allergan, terminated the partnership in 2020, leaving the biotech on its own to continue development.
Since then, Editas has replaced its CEO twice as well as brought on and then fired a chief medical officer. Top executives overseeing the company’s finance and science have also left in recent years.
In September 2021, Editas finally revealed initial results from its trial of EDIT-101, more than two years after the study began. Data were from the first six participants in the study and, while they showed treatment to be generally safe, the therapy’s effect on vision was difficult to interpret.
Thursday’s update presents a fuller picture, but could deepen doubts about the treatment’s potential.
Two of the three patients who responded positively to treatment had two copies of the genetic mutation responsible for the form of blindness EDIT-101 is designed to treat — a degenerative retinal condition known broadly as Leber congenital amaurosis 10.
About 1,500 people in the U.S. are estimated to have LCA10 and the specific mutation Editas is targeting with EDIT-101. However, far fewer have two copies of that mutation, according to the company.
The third responding patient had only one copy of the target mutation. “But we could not see in that person, was there some characteristic at baseline that would help pre-identify them and separate from the other 11 [patients with one copy],” said O’Neill.
In the study, Editas assessed changes in vision using measures of visual acuity and function, as well as a maze-like test designed to gauge functional sight. Study participants also answered questions related to their quality of life. A positive response was defined as clinically meaningful improvement in visual acuity, as well improvements in two of the other measures.
Treatment was generally well tolerated, Editas said, with most side effects rated as mild or moderate. Half of reported adverse events were related to subretinal injection used to deliver EDIT-101 into the eye.
While Editas plans to seek a development partner for EDIT-101 moving forward, it’s not clear it will be able to find one easily, according to Mani Foroohar, an analyst at SVB Securities.
“[T]he limited commercial opportunity — and the complexity and expense of developing an ocular gene editing product — suggests any partnership terms with a [net present value greater than 0] for Editas are unlikely,” he wrote in a Thursday note to clients.
“We are looking to the kind of organization that is interested and has some capabilities in gene therapies, ocular disease and has a business model that would support looking after or targeting ultra-rare or very small patient populations," said O’Neill. “There are companies like that.”
Editas will soon disclose data for another gene editing treatment it’s developing for sickle cell disease. But there it faces competition, as genetic medicines developed by partners Vertex Pharmaceuticals and CRISPR Therapeutics, as well as Bluebird bio could reach market sooner.