NEW YORK – Beam Therapeutics on Tuesday disclosed initial clinical data, including one patient death, in a Phase I/II trial of its investigational sickle cell disease (SCD) gene-editing therapy BEAM-101.
In the BEACON trial, one patient died four months after an infusion of BEAM-101 from respiratory failure that investigators determined was likely related to busulfan, a conditioning chemotherapy that patients receive in the study, and unrelated to BEAM-101. The case was also reviewed by a data safety monitoring committee and the US Food and Drug Administration.
BEAM-101 is an investigational treatment for SCD that uses a form of gene editing known as base editing to modify the promotor regions of the HBG1/2 genes, enabling BCL11A genes to produce fetal hemoglobin. The treatment involves extracting CD34-positive hematopoietic stem cells from the patient that are edited ex vivo and infused back into the patient.
As of July, six SCD patients with severe vaso-occlusive crises (VOCs) had been dosed in the single-arm, open-label BEACON trial, in which Beam is evaluating safety and efficacy of a single dose of BEAM-101. So far, the safety profile has been consistent with what is expected with busulfan conditioning and autologous hematopoietic stem cell transplantation, according to Beam. There have not been grade 3 or higher adverse events in the trial and no serious adverse events related to BEAM-101.
In terms of efficacy, four patients with at least one month of follow-up experienced rapid and robust fetal hemoglobin induction and corresponding sickle hemoglobin reduction in non-transfused blood, according to the company. So far, investigators have not reported any instances in which patients have experienced VOCs after treatment.
"For BEAM-101 in patients with sickle cell disease, we are so far achieving a potentially differentiated clinical profile using base editing, consistent with our preclinical data and comparable to sickle cell trait, while also potentially requiring fewer days in the hospital for both mobilization and engraftment," Beam CEO John Evans said in an emailed statement.
Evans added that Beam is developing an antibody conditioning process in preclinical testing, known as the Engineered Stem Cell Antibody Evasion (ESCAPE), which could eliminate the need for chemotherapy. That could help make base-editing treatments available to a broader group of patients.
Cambridge, Massachusetts-based Beam said it will present additional data on more patients and longer follow-up at the 66th American Society of Hematology Annual Meeting in December. The company will also present preclinical data on a proof-of-concept study on ESCAPE tested in nonhuman primates.