CAMBRIDGE, Mass., Dec. 6, 2021 /PRNewswire/ -- Blueprint Medicines Corporation (NASDAQ: BPMC) today announced two Nature Medicine publications on the registration-enabling EXPLORER and PATHFINDER trials of AYVAKIT® (avapritinib), highlighting its robust efficacy and safety datasets in advanced systemic mastocytosis (Advanced SM). The publications feature overall response, patient-reported outcomes and survival data, which reinforce the durable activity of AYVAKIT. Additional new analyses underscore the treatment's impact regardless of patient subgroup or disease pathology. Based on these data, AYVAKIT was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with advanced SM in June 2021.


SM is a rare hematologic disorder driven by the KIT D816V mutation in nearly all cases. In advanced SM, the median overall survival with previously available treatment options ranges from less than six months to approximately 3.5 years, depending on the subtype.1

"Targeting the primary genetic driver of systemic mastocytosis, avapritinib has shown rapid and durable improvements in mast cell burden, patient-reported symptoms and quality of life, with a generally well-tolerated safety profile," said Daniel DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at Dana-Farber Cancer Institute, lead and senior author on the EXPLORER and PATHFINDER trial publications, respectively. "I am highly encouraged by the survival benefits observed with this therapy, including in patients with mast cell leukemia who have a particularly poor prognosis. The depth of activity achieved by avapritinib, including molecular remission of KIT D816V, sets a new benchmark for the treatment of advanced systemic mastocytosis."

"The data published today in Nature Medicine comprise the largest therapeutic dataset ever reported in advanced systemic mastocytosis, encompassing two studies enrolling approximately 150 patients with up to four years of follow-up, and reflecting our deep commitment to pioneer new science and improve outcomes for patients living with this devastating disease," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines.

In addition, Blueprint Medicines announced plans to report four SM data presentations, including an oral presentation on the EXPLORER trial, at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta on December 11-14, 2021. These datasets further illustrate the significant impact of AYVAKIT in advanced SM, showcase Blueprint Medicines' clinical leadership in SM and reflect the company's ongoing collaboration with the community to improve patient care.

Nature Medicine Publication Highlights

Across the EXPLORER and PATHFINDER studies, 148 patients with advanced SM were enrolled as of the data cutoff dates. Treatment response was evaluated using modified IWG-MRT-ECNM criteria, with the overall response rate defined as complete remission with full or partial recovery of peripheral blood counts, partial remission or clinical improvement. All responses were confirmed. The results were reported as of a data cutoff date of May 27, 2020 for the EXPLORER trial and June 23, 2020 for the PATHFINDER trial.



Response evaluable patients



Overall response rate

75% (95% CI: 62%, 86%)

75% (95% CI: 57%, 89%)

Median duration of response

38 months (95% CI, 22 months, NEa)

NEa (95% CI: NEa, NEa)

Overall survival

76% estimated 24-month rate

86% estimated 12-month rate

Note: (a) NE, not estimable.

  • Across both studies, statistically significant improvements in patient-reported symptoms were observed, as measured by the Advanced SM Symptom Assessment Form Total Symptom Score.
  • AYVAKIT showed broad activity across all advanced SM subtypes, including SM with an associated hematological neoplasm (SM-AHN). For example, substantial reductions were observed in monocytosis in patients with SM and chronic myelomonocytic leukemia, and in eosinophilia in patients with SM and chronic eosinophilic leukemia, potentially reflecting the multi-lineage involvement of the KIT D816V mutation.

AYVAKIT was generally well-tolerated, and most adverse events (AEs) were Grade 1 or 2. The most common AEs included edema, thrombocytopenia, anemia, diarrhea, nausea, fatigue, vomiting, neutropenia, headache, cognitive effects and abdominal pain. Overall, 10 percent of patients in the EXPLORER trial and 5 percent of patients in the PATHFINDER trial discontinued AYVAKIT due to treatment-related AEs. AYVAKIT is not recommended for the treatment of patients with advanced SM with low platelet counts (less than 50,000/µL), which is consistent with current patient eligibility criteria in the EXPLORER and PATHFINDER trials.

The papers, titled "Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial," and "Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial," were published online in Nature Medicine on December 6, 2021.

About AYVAKIT (avapritinib)

AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA for the treatment of two indications: adults with Advanced SM, including aggressive SM (ASM), SM-AHN and mast cell leukemia (MCL), and adults with unresectable or metastatic gastrointestinal stromal tumors (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 unresectable or metastatic GIST harboring the PDGFRA D842V mutation, and in Mainland China (AYVAKIT®) for the treatment of adults with unresectable or metastatic PDGFRA exon 18 mutant GIST.

AYVAKIT/AYVAKYT is not approved for the treatment of any other indication in the U.S., Europe or Greater China, or for any indication in any other jurisdiction by any other health authority.

Blueprint Medicines is developing AYVAKIT globally for the treatment of advanced and non-advanced SM. The FDA granted breakthrough therapy designation to AYVAKIT for the treatment of advanced SM, including the subtypes of ASM, SM-AHN and MCL, and for the treatment of moderate to severe indolent SM.

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

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of AYVAKIT in Greater China, which encompasses Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for AYVAKIT in the rest of the world.

About SM

SM is a rare disease driven by the KIT D816V mutation. Uncontrolled proliferation and activation of mast cells result in chronic, severe and often unpredictable symptoms for patients across the spectrum of SM. The vast majority of those affected have non-advanced (indolent or smoldering) SM, with debilitating symptoms that lead to a profound, negative impact on quality of life. 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.

Debilitating symptoms, including anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog, fatigue and bone pain, often persist across all forms of SM despite treatment with a number of symptomatic therapies. 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. Historically, there had been no approved therapies for the treatment of SM that selectively inhibit D816V mutant KIT.

Important Safety Information

Serious intracranial hemorrhage (ICH) may occur with AYVAKIT treatment; fatal events occurred in <1% of patients. Overall, ICH (eg, subdural hematoma, ICH, and cerebral hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT. In Advanced SM patients who received AYVAKIT at 200 mg daily, ICH occurred in 2 of 75 patients (2.7%) who had platelet counts ≥50 x 109/L prior to initiation of therapy and in 3 of 80 patients (3.8%) regardless of platelet counts. Monitor patients closely for risk of ICH including those with thrombocytopenia, vascular aneurysm or a history of ICH or cerebrovascular accident within the prior year. Permanently discontinue AYVAKIT if ICH of any grade occurs. A platelet count must be performed prior to initiating therapy. AYVAKIT is not recommended in Advanced SM patients with platelet counts <50 x 109/L. Following treatment initiation, platelet counts must be performed every 2 weeks for the first 8 weeks. After 8 weeks of treatment, monitor platelet counts every 2 weeks or as clinically indicated based on platelet counts. Manage platelet counts of <50 x 109/L by treatment interruption or dose reduction.

Cognitive adverse reactions can occur in patients receiving AYVAKIT. Cognitive adverse reactions occurred in 39% of 749 patients and in 28% of 148 SM patients (3% were Grade >3). Memory impairment occurred in 16% of patients; all events were Grade 1 or 2. Cognitive disorder occurred in 10% of patients; <1% of these events were Grade 3. Confusional state occurred in 6% of patients; <1% of these events were Grade 3. Other events occurred in <2% of patients. Depending on the severity, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue.

AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective method of contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks after the final dose.

The most common adverse reactions (≥20%) at all doses were edema, diarrhea, nausea, and fatigue/asthenia.

Avoid coadministration of AYVAKIT with strong and moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong and moderate CYP3A inducers.

To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or FDA at 1-800-FDA-1088 or

Please click here to see the full Prescribing Information for AYVAKIT.

About Blueprint Medicines

Blueprint Medicines is a global precision therapy company that invents life-changing medicines for people with cancer and hematologic disorders. Applying an approach that is both precise and agile, we create therapies 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 genomically defined cancers, systemic mastocytosis, 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, expectations regarding the potential benefits of AYVAKIT in treating patients with SM; and Blueprint Medicines' 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, risks and uncertainties related to the impact of the COVID-19 pandemic to Blueprint Medicines' business, operations, strategy, goals and anticipated milestones, including Blueprint Medicines' ongoing and planned research and discovery activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Blueprint Medicines' ability and plans in establishing a commercial infrastructure, and successfully launching, marketing and selling current or future approved products, including AYVAKIT and GAVRETO® (pralsetinib); Blueprint Medicines' ability to successfully expand the approved indications for AYVAKIT and GAVRETO or obtain marketing approval for AYVAKIT and GAVRETO in additional geographies in the future; the delay of any current or planned clinical trials or the development of Blueprint Medicines' current or future drug candidates; Blueprint Medicines' advancement of multiple early-stage efforts; 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; the pre-clinical and clinical results for Blueprint Medicines' drug candidates, which may not support further development of such drug candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; Blueprint Medicines' ability to develop and commercialize companion diagnostic tests for its current and future drug candidates; and the success of Blueprint Medicines' current and future collaborations, partnerships or licensing arrangements, including Blueprint Medicines' global collaboration with Roche for the development and commercialization of GAVRETO. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Blueprint Medicines' filings with the Securities and Exchange Commission (SEC), including Blueprint Medicines' most recent Annual Report on Form 10-K, as supplemented by its most recent Quarterly Report on Form 10-Q and any other filings that Blueprint Medicines has made or may make with the SEC in the future. 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.


1 Sperr WR, Kundi M, Alvarez-Twose I, et al. International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study. Lancet Haematol. 2019;6(12):e638-e649.


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

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