Beam reveals initial clinical data on base-edited sickle cell therapy, reports one patient death

Beam Therapeutics has provided a preliminary update on its experimental gene-edited treatment aimed at addressing severe sickle cell disease. By July 2, six patients had received the therapy, which employs base editing to activate a functional fetal form of the hemoglobin protein, according to the biotech firm.

During the Phase 1/2 trial, one patient unfortunately succumbed to respiratory failure four months post-treatment with BEAM-101. This adverse outcome was likely linked to the busulfan conditioning needed before the gene-edited therapy could be administered. Beam CEO John Evans expressed his condolences, noting the severity of the patients' conditions and the inherent risks of such curative treatments.

Following the announcement, Beam's stock experienced a 10% decline on Tuesday morning. Among the four patients who had been monitored for at least a month after receiving the treatment, the company observed that the therapy induced fetal hemoglobin levels exceeding 60% while reducing sickle cell hemoglobin by up to 36%. These effects, Beam reported, have been sustained over time. Evans highlighted that these results were comparable to those seen in asymptomatic sickle trait carriers and surpassed the outcomes reported for Vertex's approved sickle cell therapy, Casgevy.

Additionally, Beam reported a median neutrophil engraftment time of 17 days and platelet engraftment of 20 days, which Evans pointed out as being shorter than the 27 and 32 days reported for Casgevy. He emphasized that shorter engraftment times reduce hospital stays and infection risks for patients.

Beam's base editing approach allows for a precise single-letter change in the DNA without the need for double-stranded breaks, which Evans described as a gentler method on the cells. Although it is too early to determine if Beam's therapy will yield significantly different results compared to Casgevy and bluebird bio's Lyfgenia, Evans pointed to initial advantages indicated by the early data.

Despite the promise shown by Beam's therapy, there are questions about the market's enthusiasm for a third gene therapy for sickle cell disease. Editas Medicine, another company in the field, recently announced a shift away from its clinical sickle cell therapy program to focus on an in vivo approach.

The launches of the first two approved sickle cell gene therapies have been gradual. Vertex reported that 40 patients have begun the process of receiving its therapy, generating $2 million in revenue from its first dosed patient in the third quarter. Bluebird bio, on the other hand, reported 41 patient starts across its three gene therapies by late September but also revealed cost-cutting measures and layoffs.

Although Beam's data are preliminary, the company noted that no patients have experienced severe pain episodes known as VOCs, associated with sickle cell disease. Additionally, markers of hemolysis, the breakdown of blood cells, either normalized or improved in all patients treated.

The treatment process for BEAM-101 is extensive, involving the extraction and editing of patients' blood stem cells to activate fetal hemoglobin production. Patients undergo rigorous chemotherapy conditioning to make room in their bone marrow for the newly edited cells, which are then reinfused. This conditioning process carries a significant risk of infertility.

Beam shared these initial findings in an abstract released for the upcoming annual ASH meeting in December, where the company plans to present data with longer follow-up from seven patients and additional preclinical results from two monkeys that received an experimental regimen intended to eliminate the need for intensive conditioning.