Patient’s death mars other positive data for Beam’s sickle cell gene therapy

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

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

“While the patient’s death is unfortunate, we believe the event highlights the need for less toxic preconditioning options and we believe Beam is leading the space in this regard,” analysts William Blair wrote.

BEAM disclosed the data from the Phase 1/2 BEACON trial for BEAM-101 as a curtain raiser on abstracts for the American Society of Hematology meeting that is set for early December in San Diego. As of the July 2 data cut-off date, six patients had been dosed, with one month of data available for four of them.

The patient’s death, which Beam reported was due to respiratory failure four months after receiving treatment, was considered unrelated to BEAM-101 and was instead related to the conditioning treatment used to prepare patients for gene therapy . Patients received the chemotherapy agent busulfan for conditioning; Beam said the data are consistent with that drug’s known safety profile. The Data Safety Monitoring Committee and the FDA reviewed the patient’s death.

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

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

Vaso-occlusive events (VOC), the painful attacks that are a hallmark of sickle cell disease, have not been reported.

William Blair analysts said they believe BEAM-101 has a chance to push the market as a next-generation gene therapy for sickle cell. With HbF levels reaching around 65% and HbS falling below 40%, the therapy met the company’s previous expectations. This could translate into a longer interval between VOC events for patients.

Given the regulatory precedent set by early entrants, William Blair anticipates that Beam needs about 15 months of follow-up on the 35 patients currently enrolled in the BEACON trial before regulatory discussions begin.

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

Additional data from the Phase I/II study will be presented in December when the conference officially begins, which William Blair said will provide an indication of BEAM-1010’s durability and replicability.

Beam will also report preclinical data for another core-editing gene therapy candidate at ASH — 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 traditional chemotherapy. Non-human primate data showed that the conditioning treatment was well tolerated with rapid and significant induction of HbF.