BEAM-101 seems to be competitive with approved sickle cell treatments, William Blair analysts said in a note to investors, but a patient death underscores the need for less-toxic preconditioning treatments.
A first glimpse of data for Beam Therapeutics’ base editing gene therapy BEAM-101 on Tuesday morning showed a swift rise in a key biomarker for sickle cell disease at one month in all four patients that reached that milestone. But a patient death due to the conditioning treatment used muddied the results.
William Blair analysts said in a note to investors that BEAM-101 appears competitive with approved sickle cell treatments, which include CRISPR Therapeutics and Vertex Pharmaceuticals’ Casgevy and bluebird bio’s Lyfgenia. But the analysts noted that the patient death highlights the importance of safer preconditioning treatments for gene therapies.
“While the patient death is unfortunate, we see the event as highlighting the need for less-toxic preconditioning options, and we think Beam is leading the space in this regard,” William Blair analysts wrote.
Beam revealed the data from the Phase 1/2 BEACON trial for BEAM-101 as the curtain lifted on abstracts for the American Society of Hematology meeting that’s set for early December in San Diego. As of the July 2 data cutoff, six patients had been dosed, with one-month data available for four of them.
The patient death, which Beam reported occured due to respiratory failure four months after receiving treatment, was deemed unrelated to BEAM-101 and was instead linked to the conditioning treatment used to prep patients for the gene therapy. Patients received the chemotherapy agent busulfan for conditioning; Beam said the data consistent with the known safety profile of that drug. The data safety monitoring committee and the FDA reviewed the patient death.
Otherwise, BEAM-101 was not linked to any grade 3 or higher adverse events or serious adverse events.
Efficacy results were preliminary, but the four evaluable patients with one month of follow up showed rapid and robust fetal hemoglobin (HbF) induction, a biomarker for sickle cell disease that suggests clinical benefit. Beam said that the patients met the target of greater than 60% HbF induction and had sickle cell hemoglobin (HbS) reduction of 36% or less.
No vaso-occlusive (VOC) events, the painful attacks that are a hallmark of sickle cell disease, were reported.
William Blair analysts said they believe that BEAM-101 has a shot at pressuring the market as a next-generation gene therapy for sickle cell. With the achievement of HbF levels around 65% and HbS lowering below 40%, the therapy met the firm’s earlier expectations. This could translate into a longer span between VOC events for patients.
Given the regulatory precedent set by the earlier entrants to the market, William Blair anticipates that Beam needs about 15 months of follow up on the 35 patients currently enrolled in the BEACON trial before beginning regulatory discussions.
BEAM-101 also engrafted faster than other sickle cell gene therapies. Patients also 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, which does not cause DNA breaks. William Blair said that this could mean a better experience for the patient and reduced healthcare costs.
Additional data from the Phase I/II trial will be presented in December when the conference officially gets underway, which William Blair said will give a hint at BEAM-1010’s durability and replicability.
Beam will also report preclinical data for another base editing gene therapy candidate at ASH—an investigational treatment the company says could eliminate the need for conditioning treatment altogether. In that case, the preclinical study used Beam’s Engineered Stem Cell Antibody Evasion with CD117 monoclonal antibody (mAb) conditioning instead of the traditional chemotherapy. The non-human primate data showed the conditioning treatment was well tolerated with rapid and significant induction of HbF.
