Blueprint Medicines highlights ‘decade of leadership’ in Mast Cell research with new AYVAKIT and BLU-808 data at AAAAI/WAO 2025

“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. 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.”

AYVAKIT: PIONEER Three-Year Efficacy and Safety Data in ISM

• AYVAKIT 25 mg once daily (QD) was well-tolerated and no new safety signals were identified with a median of 3 years of exposure, with some patients out to five years of treatment. The most common treatment-related adverse events (AEs; ≥5 percent) were low-grade peripheral edema, periorbital edema, headache and nausea.
• AYVAKIT 25 mg QD led to robust and durable improvements in overall symptoms, individual symptom domains (skin, gastrointestinal, neurocognitive) and quality of life through 144 weeks of treatment.
• In patients who had high disease burden and escalated to AYVAKIT 50 mg QD (median follow-up: 10.6 months since escalation), treatment was well-tolerated, with side effects consistent with those reported at AYVAKIT 25 mg QD and no patients discontinuing due to AEs. Nearly all patients (93 percent) had improved or stable benefits in overall symptoms.

Low Bone Density: Positive Clinical Impact of AYVAKIT and Real-World Prevalence in ISM

• In a single-site case series from the PIONEER trial, AYVAKIT showed clinically meaningful and durable improvements in bone density, including in the lumbar spine, femoral neck and total proximal femur.
• In real-world data generated from Mayo Clinic electronic health records, 67 percent of ISM patients had osteoporosis/osteopenia compared to 34 percent in a matched control cohort (p<0.0001).

AYVAKIT: Clinical Benefits in Patients with Undetected KIT D816V by ddPCR Assay

• In the PIONEER trial, 15 percent of patients with ISM did not have KIT D816V mutations detected by the commercially available Droplet Digital Polymerase Chain Reaction (ddPCR) assay. Within this group, most patients had KIT mutations identified by the more sensitive duplex sequencing method, and these patients achieved similar reductions in serum tryptase and improvements in symptoms as those with detectable KIT mutations by the ddPCR assay.

BLU-808: Positive Healthy Volunteer Data

• In the Phase 1 single-ascending dose (SAD) and multiple-ascending dose (MAD, 14-day dosing) trial, BLU-808 was well-tolerated at all doses tested. There were no serious AEs, no discontinuations or dose modifications due to AEs, and no significant changes in laboratory measures.
• BLU-808 achieved dose-dependent serum tryptase reductions exceeding 80 percent, reflecting evidence of mast cell target engagement.
• BLU-808 had a half-life supporting once-daily oral dosing and showed sustained target coverage across a range of doses.

Blueprint Medicines’ AAAAI / WAO data presentations are listed below. Copies of the data presentations will be available in the “Science—Publications and Presentations” section of the company’s website at www.BlueprintMedicines.com.

• Oral Presentation: Assessing Real-World Natural History of Indolent Systemic Mastocytosis: Retrospective Matched Cohort Study from Mayo Clinic Electronic Health Records (Abstract 955 – Monday, March 3)
• Oral Presentation: Responses to Avapritinib in Patients without Detectable KIT Mutations by ddPCR in Peripheral Blood Highlight Diagnostic Challenges and Opportunities in Indolent Systemic Mastocytosis (Abstract 965 – Monday, March 3)
• Poster Presentation: Patient Reported Burden of Indolent Systemic Mastocytosis in White vs. Non-White Patients (Abstract 220 – Friday, February 28)
• Poster Presentation: Identification of Clonal Mast Cell Disease in Patients with Anaphylaxis or Evidence of Systemic Mast Cell Activation: A Post Hoc Analysis from PROSPECTOR (Abstract 301 – Saturday, March 1)
• Poster Presentation: Avapritinib Impacts the Plasma Inflammatory Proteome in Patients with Indolent Systemic Mastocytosis (Abstract 517 – Saturday, March 1)
• Poster Presentation: Multiple Proteins Correlate with Tryptase Levels in Patients with Indolent Systemic Mastocytosis (ISM): Preliminary Results of Plasma Proteomic Analysis in PIONEER (Abstract 518 – Saturday, March 1)
• Poster Presentation: Comprehensive Analysis of Immunoglobulin E Levels in Healthy Donors and Patients with Indolent Systemic Mastocytosis Enrolled on the PIONEER Trial of Avapritinib (Abstract 521 – Saturday, March 1)
• Poster Presentation: Avapritinib and Bone Health in Indolent Systemic Mastocytosis: Learnings from the PIONEER Trial (Abstract 527– Saturday, March 1)
• Poster Presentation: PREDICT-SM: Development of Machine Learning Models to Support Screening for Undiagnosed Systemic Mastocytosis (Abstract 530 – Saturday, March 1)
• Poster Presentation (Trial in Progress): HARBOR: An Ongoing Phase 2/3 Study of Elenestinib in Patients with Indolent Systemic Mastocytosis (Abstract 533 – Saturday, March 1)
• Poster Presentation: Long-Term Quality of Life and Safety in Patients with Indolent Systemic Mastocytosis Treated with Avapritinib in the PIONEER Study (Abstract 534 – Saturday, March 1)
• Poster Presentation: BLU-808: A Potent and Selective Oral Small Molecule Wild-Type KIT Tyrosine Kinase Inhibitor for Allergic Conditions (Abstract 535 – Saturday, March 1)
• Poster Presentation: Utility of Large Language Models to Quantify Diagnostic Delays in Systemic Mastocytosis: A Multi-Center Real World Study (Abstract 544 – Saturday, March 1)
• Poster Presentation: Safety and Pharmacokinetics (PK) of BLU-808 Following Oral Dosing in Healthy Volunteers (Abstract 698 – Sunday, March 2)