Beam Therapeutics reports Phase 1/2 BEACON trial results showing risto-cel achieved >60% HbF, eliminated severe VOCs, and improved anemia in sickle cell disease.
Written By: Dr. Anuja Badgujar BDS
Reviewed By: Pharmacally Editorial Team
Beam Therapeutics has reported interim results from the Phase 1/2 BEACON trial evaluating ristoglogene autogetemcel (risto-cel; formerly BEAM-101) in patients with sickle cell disease (SCD) and severe vaso-occlusive crises (VOCs). The data demonstrate consistent efficacy, manageable safety, and improved treatment feasibility, supporting a differentiated profile with potential best-in-class characteristics.
The results have also been published in The New England Journal of Medicine.
The ongoing, open-label, multicenter study included 31 treated patients as of August 6, 2025, with follow-up ranging from 0.3 to 20.4 months. Adult and adolescent cohorts were fully enrolled in mid-2025, and manufacturing of all doses was completed by December 2025.
Risto-cel is a one-time autologous, base-edited cell therapy composed of CD34+ hematopoietic stem and progenitor cells. It modifies the HBG1/2 promoter regions to inhibit binding of the transcriptional repressor BCL11A without disrupting its expression, leading to sustained production of non-sickling fetal hemoglobin (HbF) and reduction of sickle hemoglobin (HbS).
Clinical Outcomes
Risto-cel demonstrated clinically meaningful and durable benefits. Patients achieved fetal hemoglobin levels above 60% with a corresponding reduction in sickle hemoglobin to below 40%, resulting in a protective hemoglobin profile similar to sickle cell trait. These changes led to rapid and sustained hematologic improvement.
All treated patients achieved resolution of anemia following discontinuation of transfusions, and markers of hemolysis improved or normalized. No severe vaso-occlusive crises were reported after engraftment. Red blood cell sickling parameters decreased to levels comparable to those seen in individuals with sickle cell trait, indicating a functional disease-modifying effect.
Safety and Feasibility
The safety profile of risto-cel was consistent with myeloablative conditioning using busulfan and autologous hematopoietic stem cell transplantation (HSCT), with no new safety signals identified.
Operational metrics supported treatment feasibility and scalability. Most patients required only a single stem cell collection cycle. The median manufacturing time was 2.9 months, and the median time from collection to dosing was 4.5 months. Patients experienced rapid and robust bone marrow engraftment, demonstrating efficient treatment delivery and recovery across multiple centers.
Expert and Company Insights
Clinical investigators, including Matthew M. Heeney, noted that risto-cel demonstrated encouraging efficacy with sustained induction of fetal hemoglobin and elimination of severe vaso-occlusive crises following engraftment. These findings suggest the therapy may reduce disease complications and improve long-term outcomes for patients with SCD.
Ashish Gupta highlighted improvements in operational aspects of therapy, including fewer cell collection cycles, rapid engraftment, and reduced transfusion requirements, which may enhance patient experience and reduce resource utilization.
Amy Simon stated that risto-cel reflects the company’s base editing approach to developing precision genetic medicines designed to deliver robust and durable clinical benefit. The company plans to submit a Biologics License Application (BLA) as early as late 2026.
Regulatory Status
Risto-cel has received multiple designations from the U.S. Food and Drug Administration, including Orphan Drug Designation and Regenerative Medicine Advanced Therapy (RMAT) designation. It has also been included in the Chemistry, Manufacturing, and Controls Development and Readiness Pilot (CDRP) program, supporting accelerated development and regulatory review.
Disease Background
Sickle cell disease is caused by a mutation in the beta-globin gene that leads to formation of hemoglobin S (HbS), resulting in red blood cell sickling, hemolysis, and vaso-occlusion. The disease is associated with chronic anemia, severe pain crises, organ damage, and reduced life expectancy. It affects approximately 100,000 individuals in the United States and millions worldwide.
Interim BEACON trial results show that risto-cel induces sustained fetal hemoglobin, eliminates severe vaso-occlusive crises post-engraftment, and improves key disease markers. These findings support its potential as a disease-modifying, gene-edited therapy for sickle cell disease.
Reference
Beam Therapeutics Announces Publication of BEACON Phase 1/2 Data for risto-cel in Patients with Sickle Cell Disease (SCD) in The New England Journal of Medicine, 01 April 2026, https://investors.beamtx.com/news-releases/news-release-details/beam-therapeutics-announces-publication-beacon-phase-12-data
Ashish O. Gupta et al, Base Editing of HBG1 and HBG2 Promoters for Sickle Cell Disease, New Eng J Med, Published April 1, 2026, https://www.nejm.org/doi/full/10.1056/NEJMoa2504835
About the Writer
Dr. Anuja Badgujar, BDS, is a dentist with expertise in US healthcare data and medical data annotation. With four years of experience handling US healthcare datasets, she brings strong domain knowledge and precision to her work. She is also deeply passionate about medical writing, with a focus on translating complex medical information into clear and structured content.