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Blueprint Medicines reports clinical data highlighting leadership in developing targeted treatment options for patients with systemic mastocytosis

95 percent confirmed overall response rate and 37 percent confirmed complete remission rate in treatment-naïve patients with SM-AHN, the most common subtype of advanced SM, in PATHFINDER trial of AYVAKIT® (avapritinib). Ongoing survival benefits, with up to six years of follow-up, in patients with advanced SM from EXPLORER trial of AYVAKIT. Top-line, 12-week Part 1 data from HARBOR trial show elenestinib (BLU-263) improved measures of mast cell burden and patient-reported symptoms in indolent systemic mastocytosis (SM)

CAMBRIDGE, Mass., Dec. 11, 2022 /PRNewswire/ — Blueprint Medicines Corporation (NASDAQ: BPMC) today announced AYVAKIT® (avapritinib) data showing high, durable response rates and prolonged overall survival (OS) in patients with advanced systemic mastocytosis (Advanced SM), including SM with an associated hematological neoplasm (SM-AHN). The findings are being reported in two presentations, including an oral presentation featuring updated follow-up from treatment-naïve patients in the PATHFINDER trial, at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition in New Orleans. AYVAKIT is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with Advanced SM.

SM is a rare hematologic disorder driven by the KIT D816V mutation in approximately 95 percent of cases. In advanced SM, the median OS has ranged from less than six months to approximately 3.5 years, depending on the subtype.1 AYVAKIT was designed to potently and selectively inhibit D816V mutant KIT.

“AYVAKIT has demonstrated significant clinical benefits in patients with advanced systemic mastocytosis, including complete remissions and durable responses that have translated into a highly meaningful impact on overall survival,” said Deepti Radia, M.D., a hematologist and an investigator on the PATHFINDER and EXPLORER trials. “As a physician specializing in SM and other myeloproliferative neoplasms, I am encouraged that treatment-naïve patients with SM-AHN had a 95 percent response rate and an estimated two-year survival rate of 86 percent in the PATHFINDER trial. Before the introduction of KIT D816V-targeted therapy, physicians often focused on treating the AHN component of SM-AHN. AYVAKIT represents a practice-changing advancement for this patient population, and updated PATHFINDER data highlight the importance of treating the SM for early therapeutic intervention in SM-AHN patients with measurable ‘C’ findings, excluding those with aggressive AHNs.”

“AYVAKIT has become the standard of care treatment for advanced systemic mastocytosis in the U.S., with a growing number of patients receiving the therapy early in the course of their disease. This position is further reinforced by updated AYVAKIT results in the treatment-naïve setting, which include overall response, complete remission and survival rates that establish a new benchmark for patients with advanced SM,” said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. “Through our long-term partnership with the SM community, we have amassed datasets reflecting hundreds of patient years of clinical experience across advanced and non-advanced forms of the disease. This breadth of data highlights strong clinical execution and reflects our leadership in developing a portfolio of targeted treatment options designed to address the medical needs of patients with SM.”

AYVAKIT – Updated data from the PATHFINDER and EXPLORER trials in advanced SM

Long-term follow-up of 38 treatment-naïve patients from the PATHFINDER trial and 69 patients from the EXPLORER trial – regardless of line of therapy – further validate the clinical efficacy and safety profile of AYVAKIT in advanced SM. Based on modified IWG-MRT-ECNM criteria, the overall response rate (ORR) was defined as complete remission with full or partial recovery of peripheral blood counts (CR/CRh), partial remission or clinical improvement. All responses were confirmed.

In the PATHFINDER trial, AYVAKIT showed broad clinical activity in treatment-naïve patients evaluable for response (n=25), including those with SM-AHN (n=19), as of a data cutoff date of April 20, 2021.

For treatment-naïve patients across advanced SM subtypes:

  • ORR was 84 percent and CR/CRh rate was 32 percent.
  • Median time to response was two months and median time to CR/CRh was six months.
  • Median duration of response (DOR) has not been reached.
  • Estimated 24-month OS rate was 88 percent.

For treatment-naïve patients with SM-AHN:

  • ORR was 95 percent and CR/CRh rate was 37 percent.
  • Estimated 24-month OS rate was 86 percent.

In addition, improvements were observed across hematologic parameters, such as monocytes and eosinophils in the peripheral blood, suggesting multi-lineage involvement of the KIT D816V mutation.

In the EXPLORER trial, 57 patients across lines of therapy were evaluable for response as of a data cutoff date of April 5, 2022. The ORR was 77 percent, with median DOR and OS not reached in patients followed for up for six years.

Safety data from the PATHFINDER and EXPLORER trials were consistent with previously reported results and the FDA approved labeling for AYVAKIT, and reinforce the favorable benefit-risk profile of AYVAKIT at the 200 mg once-daily (QD) recommended dose. The most common treatment-related adverse events (AEs) included periorbital edema, thrombocytopenia, peripheral edema, anemia and nausea. Discontinuations due to treatment-related AEs occurred in four treatment-naïve patients (11 percent) since the initiation of the PATHFINDER trial in 2018, and seven patients across lines of therapy (10 percent) since the initiation of the EXPLORER trial in 2016.

Copies of Blueprint Medicines data presentations from the ASH annual meeting are available in the “Science—Publications and Presentations” section of the company’s website at

Elenestinib (BLU-263) – Top-line results from Part 1 of HARBOR trial in indolent SM

In addition, Blueprint Medicines today announced top-line, 12-week results from the dose-finding Part 1 of the HARBOR trial of elenestinib, a next-generation KIT D816V inhibitor, reflecting the company’s long-term commitment to SM. HARBOR Part 1 was designed to assess concurrent dose cohorts of elenestinib plus best available therapy (elenestinib group) versus placebo plus best available therapy (placebo group) in patients with indolent SM. The trial included 29 patients in the elenestinib group (n=10 at 25 mg QD; n=10 at 50 mg QD; n=9 at 100 mg QD), and 10 patients in the placebo group.

Elenestinib showed evidence of clinical activity and safety consistent with its preclinical profile and a completed Phase 1 healthy volunteer trial. Elenestinib treatment led to rapid improvements in objective measures of mast cell burden, including serum tryptase and KIT D816V allele fraction, and total symptom score (TSS) as measured by the Indolent SM Symptom Assessment Form (ISM-SAF). At 12 weeks, elenestinib demonstrated similar reductions in TSS across dose cohorts. In addition, consistent with previously reported data from the PIONEER trial of AYVAKIT in indolent SM, change in serum tryptase was not correlated with change in TSS. Safety results show that elenestinib was generally well-tolerated, and there were no discontinuations due to AEs. Blueprint Medicines plans to present data from Part 1 of the HARBOR trial at a medical congress in 2023.

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

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 Systemic Mastocytosis

Systemic mastocytosis (SM) is a rare disease primarily driven by the KIT D816V mutation. 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 non-advanced (indolent or smoldering) 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 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 our scientific innovation into a broad pipeline of important approved and investigational precision therapies aimed at addressing difficult-to-treat cancers and blood disorders. Today, we are delivering our approved medicines to patients in the United States, Europe, and in other geographies ourselves or through our partners. In addition, 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 expectations regarding the potential benefits of AYVAKIT for the treatment of patients with SM; statements regarding plans and expectations for Blueprint Medicines’ current or future approved drugs and drug candidates; 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 continuing to establish and expand a commercial infrastructure, and successfully launching, marketing and selling current or future approved products; Blueprint Medicines’ ability to successfully expand the approved indications for AYVAKIT/AYVAKYT and GAVRETO® (pralsetinib) or obtain marketing approval for AYVAKIT/AYVAKYT 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 preclinical and clinical results for Blueprint Medicines’ drug candidates, which 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; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials; Blueprint Medicines’ ability to obtain, maintain and enforce patent and other intellectual property protection for AYVAKIT/AYVAKYT or any drug candidates it is developing; Blueprint Medicines’ ability to develop and commercialize companion diagnostic tests for AYVAKIT/AYVAKYT or any of its current and future drug candidates; Blueprint Medicines’ ability to successfully expand its operations, research platform and portfolio of therapeutic candidates, and the timing and costs thereof; Blueprint Medicines’ ability to realize the anticipated benefits of its executive leadership transition plan; and the success of Blueprint Medicines’ current and future collaborations, financing arrangements, partnerships or licensing arrangements. 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.

SOURCE Blueprint Medicines Corporation

AYVAKIT systemic mastocytosis

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