Patient Demise Shadows Generally Favorable Results for Beam’s Sickle Cell Genetic Treatment
On Tuesday morning, initial data from Beam Therapeutics’ gene therapy, BEAM-101, demonstrated a rapid increase in a crucial biomarker related to sickle cell disease after one month, with all four patients reaching this milestone. However, the results were complicated by a report of a patient death linked to the conditioning treatment.
Analysts from William Blair indicated in their communication to investors that BEAM-101 appears to be a strong competitor against existing sickle cell therapies, such as CRISPR Therapeutics and Vertex Pharmaceuticals’ Casgevy, along with bluebird bio’s Lyfgenia. They emphasized that the occurrence of patient death underscored the urgent need for safer preconditioning protocols in gene therapies.
“While the loss of a patient is regrettable, it underlines the necessity for less harmful preconditioning alternatives, and we believe Beam is at the forefront of this endeavor,” William Blair analysts commented.
Beam disclosed the data from the Phase 1/2 BEACON trial for BEAM-101 just as the abstracts for the upcoming American Society of Hematology meeting were introduced, set to take place in early December in San Diego. As of data cutoff on July 2, six patients had been treated, with one-month data available for four of them.
The reported patient death occurred due to respiratory failure four months post-treatment and was identified as unrelated to BEAM-101, instead attributed to the conditioning regimen employed prior to the gene therapy. The conditioning involved the chemotherapy agent busulfan, with Beam stating that the safety data aligns with established profiles of this drug. Both the data safety monitoring committee and the FDA were involved in the review of this case.
Notably, BEAM-101 was not associated with any grade 3 or higher adverse reactions or serious adverse events.
While the efficacy findings are preliminary, the four patients evaluated after one month exhibited rapid and substantial induction of fetal hemoglobin (HbF), a crucial biomarker suggesting potential clinical benefits for sickle cell disease. Beam confirmed that all patients surpassed the threshold of 60% HbF induction, with sickle cell hemoglobin (HbS) levels decreased by 36% or less.
No vaso-occlusive crises, which are painful episodes typical in sickle cell disease, were reported.
According to William Blair analysts, they believe BEAM-101 has the potential to disrupt the market as an innovative gene therapy for sickle cell. The achievement of HbF levels around 65% and an HbS reduction below 40% exceeded their prior expectations, indicating a possibility of extending the intervals between vaso-occlusive episodes for patients.
In light of regulatory precedents established by earlier market entrants, William Blair projects that Beam will require roughly 15 months of follow-up for the 35 patients currently enrolled in the BEACON trial before initiating regulatory discussions.
Additionally, BEAM-101 demonstrated faster engraftment compared to other sickle cell gene therapies. Patients received an average of 1.5 treatment cycles, which the company attributes to the less invasive nature of base editing that avoids DNA breaks. William Blair noted this could lead to improved patient experiences and lower healthcare expenditures.
Further findings from the Phase I/II trial are expected to be shared in December when the conference commences, which William Blair indicated will offer insights into BEAM-101’s durability and reproducibility.
Beam will also present preclinical data regarding another base editing gene therapy candidate at the ASH meeting—an experimental treatment that the company claims could potentially eliminate the necessity for conditioning treatment entirely. In this instance, the preclinical work incorporated Beam’s Engineered Stem Cell Antibody Evasion alongside CD117 monoclonal antibody conditioning, deviating from traditional chemotherapy methods. Non-human primate findings indicated that this conditioning protocol was well tolerated and led to rapid and significant induction of HbF.