Base-Editing HSC Therapy Enrolls First Patient With Sickle Cell Disease

Beam Therapeutics has enrolled the first patient with sickle cell disease (SCD) in the phase 1/2 BEACON clinical trial (NCT05456880) of the CRISPR base-editing therapy BEAM-101.

“The enrollment of the first patient in our BEACON trial is a significant step forward for Beam and for the field of base editing,” John Evans, chief executive officer, Beam Therapeutics, said in a statement. “With the potency and precision of base editing, we believe BEAM-101 could be a best-in-class option for SCD patients with several advantages over other available genetic therapies. We are now focused on activating additional clinical trial sites in the US, modifying the BEACON protocol to enable expedited future patient enrollment and endpoint assessment, and finalizing our commercial-ready manufacturing process. We look forward to advancing this program for patients who suffer from the painful and debilitating consequences of SCD.”

BEAM-101 is a base-edited autologous hematopoietic stem cell (HSC) investigational therapy that mimics single nucleotide polymorphisms that cause persistence of fetal hemoglobin to inhibit hemoglobin S polymerization.The therapy’s base editing is designed to avoid double stranded breaks. In preclinical studies, the therapy achieved over 90% of alleles edited in HSCs, consistent upregulation of fetal hemoglobin (over 60% of total hemoglobin), and reductions in hemoglobin 6 (less than 40% of total hemoglobin, levels similar to SCD carriers).

READ MORE: The State of Gene and Cell Therapy for Sickle Cell Disease

The open-label, multicenter, single-arm BEACON trial is enrolling up to 15 participants in the phase 1 arm with SCD to evaluate the safety and preliminary efficacy of BEAM-101. Participants must be aged between 18 and 35 years with documented SCD with βS/βS, βS/β0, or βS/β+ genotypes and at least 4 severe VOCs in the 24 months prior to screening with standard of care measures.

Primary endpoints of the study include the number of severe vascular-occlusive crises (VOCs), success of and time to neutrophil engraftment, time to platelet engraftment, mortality, and severity of adverse events (AEs). Secondary outcomes include at least a 75% reduction in severe VOCs, the proportion of patients with no severe VOCs,proportion of patients with fetial hemoglobin of at least 30%, and changes in incidence and duration of hospitalizations for VOCs; red blood cell transfusions for SCD-related indications; hemoglobin concentration; lactate dehydrogenase; total bilirubin; free hemoglobin; and reticulocyte count.

Participants will undergo transfusion and mobilization for HSC retrieval. Following HSC editing, participants will be conditioned with chemotherapy and then have HSCs transplanted back. An initial sentinel cohort of 3 patients will be treated 1 at a time to confirm successful engraftment, followed by dosing in up to a total of 45 patients.

REFERENCE

Beam Therapeutics enrolls first patient in BEACON clinical trial of BEAM-101 base editing therapy candidate for the treatment of sickle cell disease. News release. Beam Therapeutics. November 14, 2022. https://www.globenewswire.com/news-release/2022/11/14/2554716/0/en/Beam-Therapeutics-Enrolls-First-Patient-in-BEACON-Clinical-Trial-of-BEAM-101-Base-Editing-Therapy-Candidate-for-the-Treatment-of-Sickle-Cell-Disease.html