BEAM-101 shows sustained benefits as treatment for sickle cell
One-year data from BEACON trial encouraging, company says
BEAM-101, a one-time, gene-edited cell therapy, continues to show durable therapeutic benefits more than one year after treatment in people with sickle cell disease (SCD), according to new data from the Phase 1/2 BEACON trial.
The treatment’s developer, Beam Therapeutics, shared data from the first 17 patients dosed in the trial in a presentation, “Base editing for sickle cell disease: ongoing results from the BEACON study evaluating the safety and efficacy of BEAM-101, the first base-edited autologous CD34+ HSPC one-time cell therapy, at the European Hematology Association Congress, held June 12-15 in Milan.
Twenty-six patients have been treated in the ongoing study, which aims to dose a total of 30 people. Additional data is expected by the end of the year.
“We remain highly encouraged by the potential of BEAM-101, with today’s data further building on its potential to deliver a transformative treatment for patients with SCD,” John Evans, Beam’s CEO, said in a company press release. “We continue to see growing evidence of differentiated outcomes for BEAM-101 and base editing in severe SCD, now observed across 17 patients with the longest follow-up of over one year.”
SCD is caused by mutations that result in the production of a faulty version of adult hemoglobin, the protein that enables red blood cells to carry oxygen throughout the body. This defective hemoglobin, also called sickle hemoglobin (HbS), causes red blood cells to adopt a rigid, sickle shape, making them more prone to clumping and blocking small blood vessels, triggering painful vaso-occlusive crises (VOCs) and other SCD symptoms.
Reactivating HbF
BEAM-101 is designed to counteract the effects of HbS by reactivating the production of fetal hemoglobin (HbF), a form of hemoglobin naturally present before birth but typically replaced by adult hemoglobin soon after.
The therapy employs base editing, a highly precise gene-editing technique that modifies a single DNA letter without cutting the DNA strand. A patient’s hematopoietic stem cells, the cells responsible for producing all blood cell types, are collected and edited in the lab to increase HbF expression. After the patient undergoes conditioning chemotherapy with busulfan to eliminate existing stem cells, the modified cells are infused back into the patient, where they are expected to produce HbF-rich red blood cells.
The BEACON trial (NCT05456880), which began dosing last year, is evaluating the safety and efficacy of BEAM-101 in people with severe SCD, ages 18-35, who have had at least four VOCs in the two years before joining the trial.
Earlier data had shown that BEAM-101 displayed signs of efficacy. The new data revealed that all 17 patients treated with BEAM-101 achieved strong reactivation of HbF, with levels exceeding 60% of their total hemoglobin. Simultaneously, the proportion of HbS was durably reduced below 40%. These levels are comparable to those associated with a milder or asymptomatic clinical course, similar to that seen in people with sickle cell trait, who typically do not experience SCD symptoms.
The changes were accompanied by a rapid rise in total hemoglobin levels and resolution of anemia, a condition in which the body lacks enough healthy red blood cells to carry oxygen efficiently. These effects were sustained for up to 15.1 months in patients who had reached that point after treatment.
Engraftment, the process by which transplanted stem cells begin producing new blood cells, was rapid and consistent. Neutrophils (a type of white blood cell) recovered in a median of 16.5 days, while platelets (blood cells essential for clotting) recovered by 19.5 days.
No VOCs were reported after engraftment. Additional improvements were seen in key indicators of red blood cell health and oxygen delivery capacity.
The treatment’s safety profile was in line with expectations for stem cell transplant following busulfan. Common side effects included inflammation of the mucous membranes in the mouth (stomatitis), fever associated with low white blood cell count (febrile neutropenia), and temporary anemia. No safety issues were linked to the gene therapy itself.
“There is significant demand for new, safe and effective treatments amongst patients living with SCD, many of whom grapple with severe symptoms that have a marked impact on their quality of life and lifespan,” said trial investigator Ashish Gupta, MD, a pediatric blood and marrow transplant physician and associate professor at the University of Minnesota. “These promising and consistent new data from the BEACON trial, now from 17 patients treated with BEAM-101, continue to reinforce the potential of this gene therapy to fulfill this unmet need.”
BEAM-101 has received orphan drug designation from the U.S. Food and Drug Administration. This status comes with advantages including market exclusivity, economic incentives, and assistance with the regulatory approval process.
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