The death of a patient affects otherwise positive data on Beam’s sickle cell gene therapy

A first look at data from Beam Therapeutics’ base-editing gene therapy BEAM-101 on Tuesday morning showed a rapid increase in a key biomarker for sickle cell disease after one month in all four patients who reached the milestone. But the death of a patient due to the conditioning treatment used skewed the results.

William Blair analysts said in a note to investors that BEAM-101 appears to be competitive with approved sickle cell disease treatments, which include CRISPR Therapeutics’ Casgevy and Vertex Pharmaceuticals and Bluebird Bio’s Lyfgenia. But analysts noted that the patient’s death underscores the importance of safer preconditioning treatments for gene therapies.

“While the patient’s death is unfortunate, we view the event as a sign of the need for less toxic preconditioning options, and we believe Beam is a leader in this regard,” analysts at William Blair wrote.

beam revealed the data from the Phase 1/2 BEACON trial for BEAM-101 as the curtain rose on abstracts for the American Society of Hematology meeting scheduled to take place in San Diego in early December. At the time of the data cutoff on July 2, six patients had been treated, with one-month data available for four of them.

The patient’s death, which Beam said was due to respiratory failure four months after treatment, was not linked to BEAM-101 and was instead related to the conditioning treatment used to prepare patients for gene therapy. For conditioning, the patients received the chemotherapy drug busulfan; Beam said the data is consistent with the known safety profile of this drug. The Data Safety Monitoring Committee and FDA reviewed the patient’s death.

Otherwise, BEAM-101 was not associated with grade 3 or higher adverse events or serious adverse events.

Efficacy results were preliminary, but the four evaluable patients showed rapid and robust induction of fetal hemoglobin (HbF), a biomarker of sickle cell disease, at one month of follow-up, suggesting clinical benefit. Beam said patients achieved the goal of HbF induction of greater than 60% and had a reduction in sickle cell hemoglobin (HbS) of 36% or less.

No vaso-occlusive (VOC) events, the painful attacks that are a hallmark of sickle cell anemia, were reported.

William Blair analysts said they believe BEAM-101 has a good chance of putting pressure on the market as a next-generation gene therapy for sickle cell anemia. By achieving HbF levels of 65% and HbS reduction below 40%, the therapy met the company’s previous expectations. This could result in a longer time between VOC events for patients.

Given the regulatory precedent set by prior market participants, William Blair expects Beam to require approximately 15 months of follow-up of the 35 patients currently enrolled in the BEACON trial before beginning regulatory discussions.

BEAM-101 also engrafted faster than other sickle cell gene therapies. Additionally, patients required an average of 1.5 cycles to receive treatment, which the company said could be due to the less invasive nature of base editing that does not cause DNA breaks. William Blair said this could mean a better experience for the patient and lower healthcare costs.

Further data from the Phase I/II study will be presented in December when the conference officially begins. William Blair said they would provide an indication of the durability and reproducibility of BEAM-1010.

Beam will also publish preclinical data at ASH for another base-editing gene therapy candidate, an investigational treatment that the company says could eliminate the need for conditioning treatment altogether. In this case, the preclinical study used Beams Engineered Stem Cell Antibody Evasion with CD117 monoclonal antibody (mAb) conditioning instead of conventional chemotherapy. The non-human primate data showed that the conditioning treatment was well tolerated and caused a rapid and significant induction of HbF.