Adolescent enrollment complete in RUBY gene-editing therapy trial
Trial will evaluate reni-cel efficacy, safety in 12- to 50-year-olds
Enrollment has been completed in the adolescent group of the Phase 1/2/3 RUBY clinical trial testing Editas Medicine’s gene-editing therapy, renizgamglogene autogedtemcel (reni-cel), in people with sickle cell disease (SCD).
“I am proud of the Editas team’s work and our advancement in the first half of 2024 as we move closer to becoming a commercial-stage company and continue developing clinically differentiated, transformational medicines for people living with serious, previously untreatable diseases,” Gilmore O’Neill, president and CEO of Editas, said in a company press release.
The RUBY clinical trial (NCT04853576) aims to evaluate the efficacy, safety, and tolerability of reni-cel in 45 people with severe SCD, ages 12 through 50. Enrollment had previously been completed in the study’s adult cohort, with dosing underway. The company is working to manufacture the therapy for the first group of adolescent patients.
Editas said it’s on track to share “a substantive clinical data set of sickle cell patients with considerable clinical follow-up in the RUBY trial” by the end of the year.
SCD is caused by mutations in a gene that’s needed to make the adult version of hemoglobin, the protein that red blood cells use to transport oxygen through the bloodstream. The abnormal hemoglobin tends to clump up inside red blood cells, deforming them into the characteristic sickle shape that gives the disease its name. The misshapen cells are prone to getting trapped inside blood vessels, blocking blood flow. This, in turn, can lead to a series of complications, including vaso-occlusive crises (VOCs).
Gene-editing therapy engineers blood cells
While SCD affects the adult version of hemoglobin, it does not affect fetal hemoglobin, which is an alternative version of the protein that’s made during early fetal development. Fetal hemoglobin normally stops being made shortly after a baby is born, though some people have a benign genetic condition that causes this version of hemoglobin to continue being produced during adulthood.
Reni-cel, previously called EDIT-301, aims to engineer SCD patients’ blood cells to carry the same genetic quirks that cause persistent fetal hemoglobin production in people with that benign genetic condition. Increased production of fetal hemoglobin can help compensate for the mutated adult version of the protein, ultimately helping to mitigate SCD symptoms and complications.
The therapy works by collecting blood stem cells from a patient’s bone marrow. The cells are engineered with reni-cel and returned to the patient through a stem cell transplant, which is preceded by a round of chemotherapy to wipe out existing stem cells and make room for the modified cells. The edited cells can then give rise to new red blood cells capable of producing fetal hemoglobin.
Editas recently presented data from 18 adults treated with reni-cel as part of the RUBY study. Findings showed that all participants were free of vaso-occlusive events, including VOCs and other complications associated with blood vessel obstruction and blood flow disruption, with up to nearly two years of follow-up. Fetal hemoglobin production also increased as expected.
“With these data, we are highly confident reni-cel is well positioned to be a differentiated, best-in-class product for the treatment of sickle cell disease,” O’Neill said.
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