BEACON Study: Initial Data for BEAM-101 Autologous HSCT in SCD Encouraging

Initial data are available from BEACON, an ongoing phase I/II, single-arm, open-label study investigating BEAM-101, an autologous CD34+ base edited hematopoietic stem cell transplant (HSCT) therapy for patients with sickle cell disease (SCD) with severe vaso-occlusive crises (VOCs). The data were presented at the 2025 Tandem Transplantation & Cellular Therapy Meetings of the ASTCT and CIBMTR in Honolulu, Hawai’i.

Researchers conducting the study reported that at this point of the study, BEAM-101 has shown promising signs in engraftment, anemia improvement, and fetal hemoglobin (Hb) induction.

“These initial data support base editing of the HBG1/2 promoters as an effective therapeutic modality for the tx [treatment] of SCD and will continue to be investigated in the ongoing BEACON study,” wrote first author Ashish O Gupta, MD, MPH, of University of Minnesota, Minneapolis, and colleagues.

The study enrolled six patients who had SCD with at least four severe VOCs in the two years before screening. This cohort had an age range of 19 to 27 years, and 50% were women. Three patients required only one mobilization cycle and three required two. After busulfan myeloablative conditioning, the patients received a single infusion of BEAM-101 and were monitored for 24 months. They received an average BEAM-101 dose of 11.9 × 10⁶ viable CD34+ cells per kilogram.

Four patients in the cohort had follow-up of one month or longer. These patients all achieved neutrophil engraftment at a median of 17 days and platelet engraftment at a median of 20 days. In these four patients, total Hb increased from a mean baseline of 9.3 g/dL to 17.9, 18.2, 11.0, and 11.8 g/dL at last time point available (LTPA). Four patients had exceeded 60% fetal Hb of non-transfused Hb by month 1 and maintained this elevation to LTPA. In four patients, hemoglobin S percentage in non-transfused blood had dropped to 36% or less by month 1 and was sustained through LTPA.

All four patients with follow-up of one month or longer saw their markers of hemolysis normalize or improve. None of the patients had any signs or symptoms associated with high total Hb, and none required intervention for high total Hb. No VOCs were reported among these patients after the BEAM-101 infusion.

None of the six patients in the study cohort experienced grade 3 or worse adverse events (AEs) or serious AEs related to the treatment.  One of the four patients with follow-up of one month or longer died of respiratory failure at four months after infusion, and death had probable relation to busulfan conditioning.

“These initial data show a safety profile for BEAM-101 consistent with busulfan conditioning and autologous HSCT,” Dr. Gupta and colleagues summarized regarding the safety results.

Reference

Gupta AO, Sharma A, Frangoul H, et al. Safety and efficacy of autologous CD34+ base edited hematopoietic stem cells (BEAM-101) for the treatment of sickle cell disease with severe vaso-occlusive crises: results from the ongoing phase 1/2 BEACON study. Abstract #720. Presented at the Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 12-15, 2025; Honolulu, Hawai’i.