ASH: After landmark FDA approvals, Editas still thinks its gene therapy differentiates itself enough from competition

On the heels of Friday’s FDA approval of not one but two gene therapies to treat sickle cell disease (SCD), Editas Medicine is sharing another slice of early data for its gene-edited candidate designed to tackle the same condition. 

The new data span 17 patients who received Edita’s renizgamglogene autogedtemcel (reni-cel), either in a phase 1/2 trial dubbed RUBY for severe SCD or in a separate phase 1/2 trial known as EdiTHAL for transfusion-dependent beta thalassemia (TDT). The results build off a previous dataset shared this summer, incorporating information from 12 more patients, and were presented on Dec. 11 at the 65th American Society of Hematology Annual Meeting and Exposition.

The gene-editing biotech assessed lead candidate reni-cel among 11 patients with SCD and six patients with TDT and found that the ex vivo asset showed a safety profile consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant. No serious adverse events tied to reni-cel have been reported.

All 11 RUBY patients are free of vaso-occlusive events (VOEs)—debilitating pain episodes—and have maintained normal hemoglobin levels and a fetal hemoglobin level of at least 40% in the five-plus months after treatment.

Reni-cel’s data are compared to Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy (exa-cel), another CRISPR-edited therapy that just received FDA approval in the indication. Interim data reported in June showed that 15 of 16 (94%) SCD patients treated with exa-cel didn’t have VOEs for at least 12 consecutive months, which was the primary endpoint measured. The benefits are expected to be lifelong, Vertex and CRISPR have said.

Another trial assessing exa-cel among TDT patients, meanwhile, showed that 89% achieved the primary endpoint of transfusion independence for at least 12 consecutive months. The FDA is scheduled to make a decision on exa-cel in that indication by March 30 of next year.

Editas has shared that in its EdiTHAL trial, all patients with TDT had an early and robust increase of total hemoglobin, above the transfusion independence threshold of 9 g/dl.

“These new and promising data with a larger patient cohort support our belief that reni-cel 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, specifically driving early and robust correction of anemia and sustained increases in fetal hemoglobin,” Baisong Mei, M.D., Ph.D., Editas’ senior vice president and chief medical officer, said in a Dec. 11 release. “We look forward to dosing additional patients and sharing further RUBY and EdiTHAL clinical updates in mid-2024.”

Editas has bet a lot on reni-cel, clearing out the majority of its pipeline earlier this year to focus efforts on the investigational medicine amid unrelenting difficult market conditions. Faced with the likelihood of an exa-cel approval, many other companies—such as Graphite Bio, Sangamo Therapeutics and Intellia-partnered Novartis—shelved their SCD candidates. In contrast, Editas doubled down on reni-cel, previously dubbed EDIT-301, funneling more cash into the program to accelerate its trial.

Now, Editas faces the tough task of differentiating reni-cel from not just exa-cel, but also bluebird bio’s Lyfgenia (lovo-cel), which was also approved Friday for patients with SCD. The therapies are long-awaited treatments for the debilitating and life-threatening disease that affects more than 100,000 Americans, most of them Black.