Beam hits hemoglobin goal in first base editing clinical data, reports death tied to conditioning drug

Beam Therapeutics has presented the first clinical data on its base editing technology. All four sickle cell disease patients in the efficacy cohort had fetal hemoglobin levels above Beam’s target—and the result achieved by Vertex’s rival therapy—but one patient died, likely as a result of the conditioning regimen.

Massachusetts-based Beam has gene editing technology that sets it apart from the first wave of CRISPR biotechs. Traditional CRISPR therapies use enzymes to make double-stranded breaks in DNA. Beam argues repairs to the DNA cause scrambling of the gene sequence at the cut site, resulting in cells of varying levels of effectiveness.

Base editing is designed to cut variability—while mitigating the risk of potentially harmful chromosomal rearrangements—by eliminating the double-stranded break step. Rather than cutting DNA, Beam uses an enzyme to convert DNA bases, for example from A to G.

Beam published initial data from the phase 1/2 BEACON trial on Tuesday, providing an early look at the potential of the platform and its BEAM-101 sickle cell therapy. The data include the three patients treated in the sentinel cohort and the first of an anticipated 42 people Beam plans to treat in the expansion cohort.

The efficacy analysis includes four patients with one to six months of follow-up. At baseline, between 4% and 17% of the patients’ hemoglobin was the functional fetal type. The participants received their last red blood cell transfusion between Day 7 and Day 22. Three of the patients were assessed at Month 2, when their fetal hemoglobin levels had risen to between 72% and 74%. The fourth patient, who received their last transfusion on Day 17, had fetal hemoglobin levels of 71% after one month.

Fetal hemoglobin levels stayed elevated in the two participants with longer follow-up, slipping to 65% in Month 5 in one patient and 67% in Month 6 in the other subject. Beam’s goal going into the trial was to increase fetal hemoglobin levels to at least 60% and decrease sickle hemoglobin to 40% or lower. The cohort is small and has limited follow-up, but, so far, Beam has achieved its target profile.

Maintaining 60%-plus levels across the trial would differentiate BEAM-101 from Vertex’s Casgevy, which won FDA approval in sickle cell after achieving and sustaining fetal hemoglobin levels of 42% to 44% in a 24-month study. Casgevy’s effect on hemoglobin allowed 93.5% of patients in Vertex’s trial to be free from severe vaso-occlusive crises (VOCs) in the 12 months after receiving the CRISPR therapy. No VOCs were reported by investigators following BEAM-101 treatment.

Beam also presented safety data on six patients. The biotech said the initial safety profile was consistent with myeloablative conditioning with busulfan and autologous hematopoietic stem cell transplant. One person died from respiratory failure, and the investigator ruled it was unrelated to BEAM-101. Beam said busulfan, a drug used to prepare patients for cell transplants, was the likely cause of the respiratory failure. No grade 3 or worse adverse events were deemed related to BEAM-101.

Beam is set to share more data at the American Society for Hematology annual meeting next month. By the time of the presentation, the biotech will have safety data on seven patients, efficacy results for six participants and longer-term follow-up on the people included in Tuesday’s release.

The updates mark the start of the release of data from a trial Beam has designed to support a filing for FDA approval. Beam has adopted a similar trial design to the studies that supported the approvals of Casgevy and bluebird bio’s Lyfgenia. The precedents suggest Beam could win approval with data on 30 patients.