Beam’s base-edited cell therapy met its primary endpoint in the BEACON trial, and a U.S. biologics license application is planned as early as year-end.
Beam Therapeutics said its base-edited cell therapy ristoglogene autogetemcel (risto-cel) met the primary efficacy endpoint of the pivotal BEACON phase 1/2 trial in sickle cell disease, supporting a planned biologics license application to the FDA as early as the end of 2026.¹ The company said a filing could be the first for a base-editing therapy, but it has not yet released detailed efficacy or safety figures.¹
“These positive topline results represent a defining milestone for risto-cel and for Beam’s base editing technology more broadly, bringing us an important step closer to delivering a potentially transformative, one-time treatment for people living with sickle cell disease,” said John Evans, CEO of Beam Therapeutics.¹
BEACON is an open-label, single-arm, multicenter study.¹ The primary efficacy endpoint was freedom from severe vaso-occlusive crises, the painful episodes that occur when sickled red blood cells block blood flow, for at least 12 consecutive months, based on independently adjudicated results.¹
According to Beam, the study also met all primary safety endpoints at a prespecified interim analysis.¹ As of the Oct. 20 data cutoff, 39 adults and 10 adolescents had been treated, and 31 patients had completed the follow-up required for the primary endpoint.¹
The study met all secondary efficacy endpoints, including freedom from inpatient hospitalization for severe crises for at least 12 consecutive months.¹ Safety findings were consistent with earlier BEACON data and with the known effects of plerixafor, cell collection, busulfan conditioning, stem cell transplantation and the underlying disease, according to the company.¹
In the published phase 1/2 analysis, enrollment was limited to patients ages 12 to 35 who had at least four severe crises in the prior two years.²
Risto-cel is built from a patient’s own CD34+ hematopoietic stem and progenitor cells, which are base-edited in the promoter regions of the HBG1 and HBG2 genes and returned through a stem cell transplant.¹ The edit is designed to keep the BCL11A repressor from binding the promoter without disrupting BCL11A expression, with the aim of raising fetal hemoglobin, a non-sickling form, and mimicking naturally occurring variants.¹
Interim data on 31 patients, published in the New England Journal of Medicine in April, came from an unplanned analysis in which no investigator-reported severe crises occurred later than 60 days after the last red-cell transfusion.²
Patients received busulfan-based myeloablative conditioning before infusion.²
Sickle cell disease results from a single point mutation in the beta globin gene that causes hemoglobin to aggregate and deform red blood cells, leading to anemia, severe pain, infections, stroke, organ failure and early death.¹ The disease affects an estimated 100,000 people in the U.S. and about 8 million worldwide.¹
Gene therapy is no longer new to the field. In December 2023, FDA approved Casgevy, from Vertex Pharmaceuticals, and Lyfgenia, from Bluebird Bio, as the first cell-based gene therapies for sickle cell disease in patients 12 and older.³
Casgevy was the first FDA-approved therapy to use CRISPR/Cas9 genome editing, while Lyfgenia carries a boxed warning for hematologic malignancy.³ Beam itself lists competition from already approved gene therapies among its risk factors.¹
Risto-cel would enter a field with two approved products.
The announcement is topline and company-reported. It does not state how many of the 31 patients achieved the primary endpoint or itemize safety events. BEACON is single-arm and open label, according to its registry record, and the release ties the results to a prespecified interim analysis.⁴
Beam’s own cautionary statements note that topline results may differ from final results, that FDA could require additional data, and that treatment effects may not prove durable over longer follow-up.¹
Beam expects to submit the application as early as the end of 2026, with detailed pivotal results planned for presentation at a medical meeting in 2027.¹ Separately, the company will present results from an earlier BEACON data cutoff in an oral presentation at the American Society of Hematology annual meeting, Dec. 12–15 in New Orleans.¹
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