On December 5, 2025 Blueprint Medicines, a Sanofi company, reported updated data reinforcing the clinical efficacy and safety of long-term AYVAKIT (avapritinib) use across the spectrum of systemic mastocytosis (SM), including indolent and advanced SM. AYVAKIT led to sustained symptom and quality-of-life benefits in indolent SM (ISM) after a median follow-up of more than three years, and extended survival rates in advanced SM after a median follow-up of more than four years. Across both forms of SM, AYVAKIT showed bone health improvements reflecting disease-modifying effects, and a safety and tolerability profile consistent with previously reported results. As part of its ongoing leadership to improve SM care, Blueprint Medicines will report one oral presentation and seven poster presentations at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, December 6–9 in Orlando, Florida.

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"Our ASH (Free ASH Whitepaper) data add to the substantial body of evidence generated since we initiated clinical development for systemic mastocytosis about a decade ago, and reflect the transformative benefits AYVAKIT has delivered since its FDA approval for advanced SM in 2021 and ISM in 2023," said Mik Rinne, M.D., Ph.D., Head of Development at Blueprint Medicines. "AYVAKIT has become the global standard of care across the spectrum of the disease, with robust datasets highlighting sustained quality-of-life benefits in ISM, favorable survival outcomes in advanced SM and a well-characterized safety profile supporting chronic treatment. Our presentations reinforce the urgency to treat the root cause of SM to mitigate its significant health complications and underscore the role of AYVAKIT as a best-in-class therapy for the long-term management of the disease."

PIONEER: Durable Symptom Control, Quality-of-Life Benefits and Bone Health Improvements in ISM, with a Multi-Year Safety Profile Similar to the 24-Week Placebo-Controlled Portion of the Trial (Poster Presentations; Abstract Numbers 2024, 5582)

In patients with ISM (N=226), AYVAKIT showed sustained improvements in overall symptoms, all symptom domains (skin, gastrointestinal, neurocognitive) and most severe symptom per the ISM Symptom Assessment Form (ISM-SAF), and in quality of life per the Mastocytosis Quality of Life Questionnaire (MC-QoL).
AYVAKIT led to durable benefits in bone health among patients receiving dual-energy X-ray absorptiometry (DXA) scans (n=79), independent of concomitant use of other treatments known to improve bone density.
With a median follow-up of more than three years, the overall trial population had a 3 percent discontinuation rate due to treatment-related adverse events (TRAEs), reflecting a best-in-class safety and tolerability profile. Edema was the most common TRAE, and the majority of these events were mild (Grade 1).
PATHFINDER: Prolonged Survival, Robust Clinical Responses and Improved Bone Health with a Consistent Safety Profile Over Time in Advanced SM (Oral Presentation; Abstract Number 1022)

In patients with advanced SM receiving first-line AYVAKIT (n=38), the median overall survival (OS) was not reached and the OS rate at 48 months was 79 percent after a median follow-up of more than four years, reflecting sustained clinical benefit.
Historically, advanced SM has been associated with poor survival.1,2 In a prior clinical trial of midostaurin, the median OS was 28.7 months for patients with advanced SM.1
In treatment-naïve patients who were response evaluable (n=30), the overall response rate (ORR) was 87 percent, and the rate of complete remissions with full or partial hematologic recovery (CR/CRh) was 43 percent.
Among patients receiving DXA scans across lines of therapy (n=56), 21 percent had low bone density at baseline. In this population, AYVAKIT significantly increased bone density versus baseline levels (p<0.05).
In patients across lines of therapy (N=107), AYVAKIT had a favorable benefit/risk profile consistent with previously reported data. Common TRAEs were edema (periorbital and peripheral), thrombocytopenia and anemia.
PATHFINDER: Survival Benefits in Intermediate- and High-Risk Patients with Advanced SM, a Historically Underserved Population (Poster Presentation; Abstract Number 5595)

This analysis included patients with advanced SM who had intermediate- and high-risk prognostic scores at baseline, as determined by the Mutation-Adjusted Risk Score (MARS).
In the treatment-naïve setting, PATHFINDER results for AYVAKIT (n=24) were indirectly compared to real-world data for midostaurin (n=43), and statistical methods were used to adjust for baseline demographic differences between the two patient populations.
AYVAKIT was associated with improved OS relative to midostaurin (Hazard Ratio [HR]: 0.08; p<0.001) in these patients, who have traditionally had the worst prognosis.
Data Presentations

Oral Presentation: Avapritinib Treatment of Patients with Advanced Systemic Mastocytosis: 4-Year Safety, Effect on Bone and First-Line Efficacy Results of the PATHFINDER Clinical Study (Abstract #1022 – Monday, December 8)
Poster Presentation: Avapritinib Achieves Deep and Durable Symptom Control with a Well-Tolerated Safety Profile in ISM: Long-Term Outcomes from PIONEER (Abstract #2024 – Saturday, December 6)
Poster Presentation: Effect of Avapritinib on Skin Lesions in Patients with Advanced Systemic Mastocytosis Using a Novel, Artificial Intelligence-Based Technology (PATHFINDER) (Abstract #2030 – Saturday, December 6)
Poster Presentation: Changes in Long-Term Bone Health in Patients Receiving Avapritinib for the Treatment of Indolent Systemic Mastocytosis in the PIONEER Study (Abstract #5582 – Monday, December 8)
Poster Presentation: Improved Overall Survival in Patients with Advanced Systemic Mastocytosis Treated with Avapritinib Versus Real-World Therapy Based on Mutation-Adjusted Risk Score (MARS) Stratification (Abstract #5595 – Monday, December 8)
Poster Presentation: An Analysis of Clonal Dynamics in Patients with Indolent Systemic Mastocytosis Treated with Avapritinib in the PIONEER Study (Abstract #5573 – Monday, December 8)
Poster Presentation: Diagnostic Evolution in Systemic Mastocytosis: Clinical Impact of WHO 2022 Criteria on Smoldering Systemic Mastocytosis Identification in PIONEER (Abstract #5578 – Monday, December 8)
Poster Presentation: Interpreting Tryptase Levels and Avoiding Common Pitfalls in Screening for Clonal Mast Cell Disease (Abstract #4774 – Monday, December 8)
At the start of its oral session and at 8:00 a.m. ET on the day of their respective poster sessions, data presentations will be available in the "Science―Publications and Presentations" section of Blueprint Medicines’ website, www.blueprintmedicines.com.

About Systemic Mastocytosis

Systemic mastocytosis (SM) is a rare disease driven by the KIT D816V mutation in about 95 percent of cases. Uncontrolled proliferation and activation of mast cells result in chronic, severe and often unpredictable symptoms across multiple organ systems. The vast majority of those affected have indolent systemic mastocytosis (ISM). Despite treatment with multiple symptom-directed therapies, patients with ISM frequently experience persistent symptoms including anaphylaxis, maculopapular rash, pruritus, diarrhea, brain fog, fatigue and bone pain, as well as long-term health complications such as osteoporosis. This burden of disease can lead to a profound, negative impact on quality of life. Patients often live in fear of severe, unexpected symptoms, have limited ability to work or perform daily activities, and isolate themselves to protect against unpredictable triggers. There were no approved therapies for ISM until 2023, when AYVAKIT received U.S. Food and Drug Administration (FDA) approval for this indication.

A minority of patients have advanced SM, which encompasses a group of high-risk SM subtypes including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL). In addition to mast cell activation symptoms, advanced SM is associated with organ damage due to mast cell infiltration – including bone lesions, malabsorption, liver dysfunction and bone marrow failure – as well as poor overall survival.

(Press release, Blueprint Medicines, DEC 5, 2025, View Source [SID1234661178])