Blueprint Medicines Corporation has officially published its data presentations that give an insight into the company’s ongoing efforts to advance the treatment for mast cell-driven diseases.
According to certain reports, the stated presentations are understood to include three-year median follow-up data from the registrational PIONEER trial, demonstrating the strong long-term efficacy and safety of AYVAKIT® (avapritinib) in patients with indolent systemic mastocytosis (ISM). This is provided alongside real-world evidence to reinforce the disease’s severity.
Apart from that, Blueprint Medicines is also set to publish positive data from the Phase 1 healthy volunteer trial evaluating BLU-808, an investigational, highly potent and selective oral inhibitor of wild-type KIT, consistent with top-line data previously announced in January 2025.
Coming back to the study focused on assessing AYVAKIT® efficacy, it saw that, when 25mg worth of this drug was administered once every day (QD), it would be well-tolerated, with no new safety signals identified. The most common treatment-related adverse events (AEs; ≥5 percent) were low-grade peripheral edema, periorbital edema, headache and nausea.
Next up, we must dig into how the same AYVAKIT 25 mg QD would also instigate robust and durable improvements in overall symptoms, individual symptom domains (skin, gastrointestinal, neurocognitive), and the overall quality of life through 144 weeks of treatment.
Turning our attention towards patients with high disease burden, they were escalated to AYVAKIT 50 mg QD (median follow-up: 10.6 months since escalation). Despite the increase in dose, the drug was well-tolerated, with side effects almost similar to those reported at AYVAKIT 25 mg QD and no patients discontinuing due to AEs. Markedly enough, almost all patients (93 percent) had improved or stable benefits in overall symptoms.
“We are incredibly proud to showcase our mast cell therapy portfolio at AAAAI / WAO, with 14 presentations highlighting more than a decade of leadership and collaboration with the mast cell disease community, including renowned medical institutions pioneering innovative research and multi-disciplinary patient care,” said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. “In ISM, new data have reinforced that AYVAKIT was very well-tolerated after multiple years of treatment, with a low discontinuation rate and safety results that have remained consistent with the safety profile from the placebo-controlled study as summarized in the FDA-approval label.”
We must also dig into how, during single-site case series from the PIONEER trial, AYVAKIT was able to show clinically meaningful and durable improvements in the context of bone density, including in the lumbar spine, femoral neck, and total proximal femur.
The significance of such a performance can be better understood once you take into account real-world data generated from Mayo Clinic electronic health records, data which showed that 67 percent of ISM patients had osteoporosis/osteopenia, as compared to 34 percent in a matched control cohort (p<0.0001).
Anyway, another detail worth a mention is rooted in almost 15 percent of patients with ISM not having any KIT D816V mutations detected by the commercially available Droplet Digital Polymerase Chain Reaction (ddPCR) assay.
In fact, within this group, most patients were deemed to have KIT mutations identified by the more sensitive duplex sequencing method. These patients achieved similar reductions in serum tryptase and improvements in symptoms as those with detectable KIT mutations by the ddPCR assay.
Hold on, we still have a few bits left to unpack, considering we still haven’t expanded upon BLU-808’s study. You see, during the Phase 1 single-ascending dose (SAD) and multiple-ascending dose (MAD, 14-day dosing) trial, the drug was well-tolerated at all doses tested.
Furthermore, it achieved dose-dependent serum tryptase reductions exceeding 80 percent.
“This updated AYVAKIT data is particularly important for clinicians considering long-term treatment options for their ISM patients. Further, we are building on our foundational expertise in ISM with our oral wild-type KIT inhibitor BLU-808, with healthy volunteer data showing a differentiated clinical profile and wide therapeutic index that supports broad development across a range of mast cell diseases. Based on these data, we are initiating multiple proof-of-concept trials, with initial data expected later this year,” said Hewes.
