Blueprint Medicines Presents Registrational Data from PIONEER Trial of AYVAKIT® (avapritinib) in Patients with Indolent Systemic Mastocytosis at 2023 AAAAI Annual Meeting

Blueprint Medicines Corporation announced detailed results from the PIONEER trial of AYVAKIT® in patients with indolent systemic mastocytosis.

  • AYVAKIT achieved a statistically significant and clinically meaningful improvement in total symptom score that deepened over time, with improvements shown across all individual symptoms
  • AYVAKIT achieved a statistically significant and clinically meaningful improvement on the Mastocytosis Quality of Life Questionnaire (MC-QoL)
  • AYVAKIT had a favorable safety profile compared to placebo, supporting potential for chronic treatment
  • Blueprint Medicines to host investor webcast tomorrow, February 27, 2023, at 8:00 a.m. ET

CAMBRIDGE, Mass., Feb. 26, 2023 /PRNewswire/ -- Blueprint Medicines Corporation (NASDAQ: BPMC) today announced detailed results from the PIONEER trial of AYVAKIT® (avapritinib) in patients with indolent systemic mastocytosis (SM). As previously reported, AYVAKIT achieved statistically significant and clinically meaningful improvements on the primary and all key secondary endpoints. New results further highlight the benefits of AYVAKIT on pathological mast cell burden, disease symptoms – including total symptom score (TSS), most severe symptom and all individual symptoms – and quality of life. Across clinical measures, improvements continued to deepen over time in patients treated with AYVAKIT through 48 weeks. AYVAKIT was well-tolerated with a safety profile favorable to placebo, and 96 percent of patients in the AYVAKIT arm opted to continue treatment in the open-label extension study.

Based on these data, Blueprint Medicines submitted a supplemental new drug application (sNDA) for AYVAKIT to the U.S. Food and Drug Administration (FDA) and a type II variation marketing authorization application (MAA) for AYVAKYT® to the European Medicines Agency (EMA) for the treatment of patients with indolent SM. The FDA has granted priority review to the sNDA for AYVAKIT with a Prescription Drug User Fee Act (PDUFA) action date of May 22, 2023, and the EMA has validated the MAA for AYVAKYT.

“Patients with indolent systemic mastocytosis may experience debilitating symptoms, including skin lesions which can flare often, daily abdominal pain and diarrhea, as well as bone pain, brain fog and fatigue. These symptoms profoundly impact quality of life, the ability to work and opportunities to spend time with family,” said Mariana Castells, M.D., Ph.D., Director, Mastocytosis Center, Brigham and Women’s Hospital, and an investigator on the PIONEER trial. “AYVAKIT was designed to target KIT D816V, the underlying cause of most cases of indolent SM, with the potential to modify the disease biology across multiple organ systems. AYVAKIT significantly reduced mast cell burden and improved patients’ symptoms and quality of life in the PIONEER trial, representing the first positive registrational study for the treatment of indolent SM. The magnitude and consistency of benefit shown by AYVAKIT highlights its potential to become a major therapeutic breakthrough.”

“The detailed PIONEER results reported today mark the culmination of a decade of research and collaboration with the systemic mastocytosis community, with the goal of transforming treatment for all patients living with SM,” said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. “AYVAKIT has shown rapid, durable and clinically meaningful benefits across trial endpoints, with improvements deepening over time, and a well-tolerated safety profile. These compelling data underscore the potential of AYVAKIT to transform the standard of care for a broad range of patients. We are collaborating with regulatory authorities to make this treatment available to people with indolent SM as quickly as possible.”

Data Highlights from the PIONEER Trial

In the randomized, double-blind, placebo-controlled part of the PIONEER trial, 141 patients received AYVAKIT 25 mg once daily plus best supportive care and 71 patients received placebo plus best supportive care (placebo) at 49 sites in 13 countries. The study included adults with an indolent SM diagnosis confirmed by central pathology review, and moderate-to-severe symptom burden despite an optimized regimen of best supportive care. All patients were able to continue symptom-directed therapy throughout the trial and, following completion of the 24-week treatment period, had the option to receive AYVAKIT in an open-label extension study. Baseline patient demographics were balanced between treatment arms and reflected significant disease burden. Disease symptoms were assessed using the Indolent SM Symptom Assessment Form (ISM-SAF).

AYVAKIT achieved rapid, durable and statistically significant reductions on all measures of pathological mast cell burden compared to placebo at 24 weeks.

Outcome measure




Proportion with ≥50% reduction in serum tryptase

53.9 %

0 %


Proportion with ≥50% reduction in KIT D816V variant allele fraction

67.8 %

6.3 %


Proportion with ≥50% reduction in bone marrow mast cell aggregates

52.8 %

22.8 %


AYVAKIT achieved a statistically significant and clinically meaningful improvement in TSS compared to placebo at 24 weeks, with improvements observed across all symptoms measured by the ISM-SAF that deepened over time.

Outcome measure




24 weeks

48 weeks

24 weeks

24 weeks

Mean change in TSS

-15.6 points

-20.2 points

-9.2 points


Proportion with ≥30% reduction in TSS

45.4 %

60.7 %

29.6 %


Proportion with ≥50% reduction in TSS

24.8 %

39.3 %

9.9 %


  • AYVAKIT achieved a statistically significant improvement in mean change in most severe symptom score compared to placebo at 24 weeks (p=0.015).

AYVAKIT achieved a statistically significant and clinically meaningful improvement in the mean percent change in Mastocytosis Quality of Life Questionnaire (MC-QoL) total score compared to placebo at 24 weeks.

Outcome measure




Mean percent change in MC-QoL total score

-34.3 %

-17.9 %


AYVAKIT was well-tolerated with a favorable safety profile compared to placebo, supporting the potential for long-term treatment.

  • Across treatment arms, most adverse events (AEs) were mild to moderate in severity, and treatment-related AEs leading to discontinuations were low for both arms (1.4% each).
  • Serious AEs were reported more frequently in the placebo arm (11.3%) compared to the AYVAKIT arm (5.0%).
  • The most common treatment-related AEs (≥5 percent) were headache (7.8% AYVAKIT vs. 9.9% placebo), nausea (6.4% AYVAKIT vs. 8.5% placebo), peripheral edema (6.4% AYVAKIT vs. 1.4% placebo), periorbital edema (6.4% AYVAKIT vs. 2.8% placebo) and dizziness (2.8% AYVAKIT vs. 7.0% placebo). Most edema AEs were Grade 1, and none led to treatment discontinuation.

Copies of Blueprint Medicines data presentations from the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting are available in the “Science—Publications and Presentations” section of the company’s website at

Investor Conference Call Information

Blueprint Medicines will host a live conference call and webcast at 8:00 a.m. ET (7:00 a.m. CT) tomorrow, February 27, 2023 to discuss the PIONEER trial data of AYVAKIT in indolent SM. The conference call may be accessed by dialing 844-200-6205 (domestic) or 929-526-1599 (international), and referring to conference ID 163491. A webcast of the call will also be available under “Events and Presentations” in the Investors & Media section of the Blueprint Medicines website at The archived webcast will be available on the Blueprint Medicines website approximately two hours after the conference call and will be available for 30 days following the call.

About AYVAKIT (avapritinib)

AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA for the treatment of adults with Advanced SM, including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL), and adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. For more information, visit This medicine is approved in Europe (AYVAKYT) for the treatment of adults with ASM, SM-AHN or MCL, after at least one systemic therapy, and adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. Please click here to see the full U.S. Prescribing Information for AYVAKIT, and click here to see the European Summary of Product Characteristics for AYVAKYT. AYVAKIT/AYVAKYT is not approved for the treatment of any other indication in the U.S. or Europe.

To learn about ongoing or planned clinical trials, contact Blueprint Medicines at or 1-888-BLU-PRNT (1-888-258-7768). Additional information is available at or

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. Most of those affected have non-advanced (indolent or smoldering) SM, and among these patients, the vast majority have indolent SM. A broad range of symptoms, including anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog, fatigue and bone pain, frequently persist in patients with non-advanced SM despite treatment with multiple symptom-directed therapies. 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. Currently, there are no approved therapies for the treatment of non-advanced SM.

A minority of patients have advanced SM, which encompasses a group of high-risk SM subtypes including ASM, SM-AHN and MCL. In addition to mast cell activation symptoms, advanced SM is associated with organ damage due to mast cell infiltration and poor survival.

About the PIONEER Trial

PIONEER is a randomized, double-blind, placebo-controlled, registrational trial evaluating AYVAKIT in patients with indolent SM. The trial includes three parts: dose-finding Part 1, registrational Part 2 and open-label extension Part 3. Key trial endpoints include the change in patient-reported disease symptoms as assessed by the ISM-SAF TSS, patient-reported quality of life, measures of mast cell burden and safety. Patients who completed Part 1 or 2 were eligible to participate in Part 3. All patients receive AYVAKIT treatment during Part 3, including those rolling over from the placebo arm. For more information about the PIONEER trial, please visit ( Identifier: NCT03731260).

About Blueprint Medicines

Blueprint Medicines is a global precision therapy company that invents life-changing therapies for people with cancer and blood disorders. Applying an approach that is both precise and agile, we create medicines that selectively target genetic drivers, with the goal of staying one step ahead across stages of disease. Since 2011, we have leveraged our research platform, including expertise in molecular targeting and world-class drug design capabilities, to rapidly and reproducibly translate science into a broad pipeline of precision therapies. Today, we are delivering our approved medicines to patients in the United States and Europe, and we are globally advancing multiple programs for systemic mastocytosis, lung cancer, breast cancer and other genomically defined cancers, and cancer immunotherapy. For more information, visit and follow us on Twitter (@BlueprintMeds) and LinkedIn.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the FDA’s approval of an sNDA for AYVAKIT for the treatment of indolent SM; expectations regarding the potential benefits of AYVAKIT in treating patients with indolent SM; statements regarding plans, timelines and expectations for interactions with the FDA, EMA and other regulatory authorities; statements regarding plans and expectations for Blueprint Medicines’ current or future approved drugs and drug candidates; the potential benefits of any of Blueprint Medicines’ current or future approved drugs or drug candidates in treating patients; and Blueprint Medicines’ financial performance, strategy, goals and anticipated milestones, business plans and focus. The words “aim,” “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation: the risk that the partial clinical hold on the VELA trial may or may not be resolved in a timely manner; there may be additional adverse events observed that could impact the extent of the partial clinical hold or Blueprint Medicines’ resolution of the partial clinical hold; there may be amendments to the trial protocol that impact the timing of the trial or evaluation of the data; preliminary activity and safety data may not be representative of more mature data; the COVID-19 pandemic may impact Blueprint Medicines’ business, operations, strategy, goals and anticipated milestones, including ongoing and planned research and discovery activities, Blueprint Medicines’ ability to conduct ongoing and planned clinical trials; the risk of delay of any current or planned clinical trials or the development of Blueprint Medicines’ current or future drug candidates; risks related to Blueprint Medicines’ ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; preclinical and clinical results for Blueprint Medicines’ drug candidates may not support further development of such drug candidates either as monotherapies or in combination with other agents or may impact the anticipated timing of data or regulatory submissions; the timing of the initiation of clinical trials and trial cohorts at clinical trial sites and patient enrollment rates may be delayed or slower than anticipated; actions of regulatory agencies may affect the initiation, timing and progress of clinical trials; risks related to Blueprint Medicines’ ability to obtain, maintain and enforce patent and other intellectual property protection for its products and current or future drug candidates it is developing; and the success of Blueprint Medicines’ current and future collaborations, financing arrangements, partnerships or licensing arrangements. Any forward-looking statements contained in this press release represent Blueprint Medicines’ views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Blueprint Medicines explicitly disclaims any obligation to update any forward-looking statements.


Blueprint Medicines, AYVAKIT, AYVAKYT and associated logos are trademarks of Blueprint Medicines Corporation.

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Company Codes: NASDAQ-NMS:BPMC