Gene-editing Therapy EDIT-301 Promising in 1st RUBY Patients

Both showed signs of engraftment with neutrophils, platelets

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A DNA strand is sliced apart by scissors.

The experimental gene-editing therapy EDIT-301 appears to be working largely as expected in the first two sickle cell disease (SCD) patients treated as part of the Phase 1/2 RUBY trial, according to new data shared by the therapy’s developer, Editas Medicine.

“These promising clinical results from the RUBY trial suggest clinical proof of concept for EDIT-301 and support our belief that EDIT-301 can be a clinically differentiated, one-time, durable medicine that can provide life changing clinical benefits to patients with severe sickle cell disease long term,” Baisong Mei, MD, PhD, senior vice president and chief medical officer at Editas, said in a press release.

EDIT-301 involves collecting a patient’s hematopoietic stem cells — cells in the bone marrow that can give rise to mature blood cells — and engineering them so they produce higher levels of fetal hemoglobin (HbF). These cells are then transplanted back into the patient where they can populate the body with cells carrying the same HbF-promoting alterations.

HbF is usually produced in early fetal development, but stops being made shortly after birth. In SCD, genetic mutations result in the production of an abnormal form of adult hemoglobin, which forms clumps in red blood cells, triggering the “sickling” that gives the disease its name. Boosting HbF production may help compensate for the faulty adult protein.

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The open-label RUBY trial (NCT04853576) aims to assess EDIT-301’s safety and effectiveness in about 40 adults, ages 18–50, with severe sickle cell. Among other criteria, patients must have had at least two vaso-occlusive crises (VOCs) a year in the years before entering the study. The trial is actively recruiting participants in the U.S. and Canada.

In a company presentation, Editas shared data from the first two patients who have been treated so far in RUBY.

Both showed signs of engraftment, meaning they had detectable blood cells showing signs of alteration. In the first patient, engraftment with neutrophils, a type of immune cell, happened 23 days after infusion, and engraftment with platelets (cell fragments involved in blood clotting) happened 19 days after infusion. In the second patient, neutrophil engraftment occurred at 29 days after infusion and platelet engraftment at 37 days.

Both had three to four VOCs a year before entering the study. At the latest follow-up — five months for the first patient, 1.5 months for the second — neither had any documented VOCs.

In the first patient, after five months, total hemoglobin levels reached 16.4 g/dL — in the normal range for a typical healthy male. The proportion of total hemoglobin made up by HbF was 45.4% at five months.

The first patient showed HbF pancellularity of over 95%, meaning nearly all red blood cells were expressing HbF. The mean HbF level was 13.8 picograms per red blood cell. According to Editas, levels of 10 picograms per red blood cell or higher are sufficient to stop sickling. These data collectively “suggest proof of concept,” according to the company.

The treatment has been well tolerated so far, with no serious safety-related events reported. All the safety-related events documented so far have been consistent with known side effects related to bone marrow stem cell transplant. None have been specifically linked to the investigational therapy.

Data from additional patients in the trial are expected next year.

“I would like to thank the participants, their families, clinicians, and colleagues at collaborating institutions that contribute to the RUBY trial,” Mei said. “We look forward to sharing further clinical updates in mid-2023,”