Editas teases tiny sickle cell sample in effort to climb back into gene editing's upper echelon

Its been a rough and tumble 2022 for Editas Medicine, marked by a new executive team, the suspension of its lead asset and navigating a clinical hold on the efficacy portion of a sickle cell program.

But the company is elevating new data of that exact asset, EDT-301, as proof that its CRISPR ambitions are far from over. The company says safety data from the first two treated sickle cell patients and efficacy data from one show that the gene editing therapy works and is durable. 

The phase 1/2 RUBY trial update, announced Tuesday, found both of the patients successfully accepted the treatment and started to produce their own blood cells. Neither of the patients have so far reported vaso-occlusive events, staples of sickle cell disease where sickled red blood cells block blood flow. No adverse events related to the treatment have been reported among either patient to date, with data being accumulated through five and 1.5 months, respectively. Editas said hemoglobulin levels in the first patient treated exceeded the necessary levels to prevent red blood cell sickling. 

The news was a very small hint of promise for Editas, which is trying to regain its footing in a crowded group of companies focused on gene editing and gene therapies.

It's been just more than a year since Editas teased early data from six patients in a phase 1/2 trial of its now-shelved lead asset EDT-101 to treat a degenerative retinal disorder.The early preview caught some flak at the time given how limited the data were, but that clearly did not deter the company's new leadership. In an interview with Fierce Biotech, Editas’ top brass acknowledged the drop of good news should not be over-interpreted.

Instead, CEO Gilmore O’Neill and Chief Medical Officer Baisong Mei, M.D., Ph.D., said the data were early evidence that preclinical potential was translating in patients. O’Neill said what they have shown from the two patients is that the ex vivo editing is being done with a high degree of precision before being reintroduced back into the patient.

“And this is why the data have a high degree of translatability and why we feel it is a good thing and reasonable to share these preliminary data,” said O’Neill.

The CEO added that the company decided to show patient data around the five-month mark because that tends to be when the engraftment—the term for the body accepting the treatment and producing new blood cells—begins to plateau. Mei said additional data to be presented Tuesday morning will show that total hemoglobin and the percentage of fetal hemoglobin increased over the course of the five months. Both of the patients featured in the interim data are Black, a notable characteristic given that one in 13 Black or African-American babies are born with the sickle cell trait. The trial is open to all patients with severe sickle cell disease, according to Mei. 

The sickle cell data come a few weeks after Editas elected to shelve its lead asset, EDT-101, as a treatment for a severe eye disease. The company previously reported that three out of 14 evaluable patients with Leber congenital amaurosis had clinically meaningful improvements following treatment, two of which were homozygous for the LCA10 gene. Electing to focus only on homozygous patients would’ve meant reducing the already-small patient population down to about 300 across the U.S.

That was evidently too few, as the company decided to pause enrollment of the corresponding BRILLIANCE trial and seek a partner. O'Neill declined to provide an update on how such discussions were going. 

At the time of the decision, O’Neill said Editas’ larger ambitions of being a top gene editing company are unchanged, challenging an investor’s characterization that the company was falling off the podium in the race for new medicines. 

“With regard to overall view of market opportunity and most importantly, the competitive intensity of the space, I think first thing I’d do is challenge the characterization that our sickle cell 301 program is fifth or sixth,” he said. “It is not; it is much higher up than that.”

Fellow sickle cell competitors with gene therapies include CRISPR Therapeutics (which is partnered with Vertex), bluebird bio and Beam Therapeutics. In light of the new data, O’Neill expanded on this confidence, saying that it's in his and Mei’s belief that there is room for more than one product in the sickle cell treatment market.

“I think another important point is that we believe … that the vast majority of the prevalent patient population with sickle cell disease, and hopefully beta thalassemia, will still be awaiting therapy at the time of our launch,” he said, adding he also believes there’s potential for EDT-301 to differentiate itself. 

It will be a few months before O’Neill may be able to speak to that hope with more confidence. According to O’Neill, additional patients have been enrolled, with their cells collected and edited but not yet infused. Editas plans to release additional data by the middle of 2023.