Midostaurin

-- Breadth of presentations, including one oral and two flash talks, showcase Blueprint Medicines' leadership role in advancing care for patients with systemic mastocytosis -- CAMBRIDGE, Mass. , June 12, 2025 /PRNewswire/ -- Blueprint Medicines Corporation (Nasdaq: BPMC) today announced data presentations reflecting over a decade of collaboration with clinical experts and patient advocates to transform the treatment of systemic mastocytosis (SM). Key results continue to position AYVAKIT®/AYVAKYT® (avapritinib) as the durable standard of care across indolent and advanced SM, and highlight the real-world burden of the disease, reinforcing the importance of treating with a therapy that addresses the root cause of SM. These data will be reported at the 2025 European Hematology Association (EHA2025) Hybrid Congress , being held June 12 to 15 in Milan, Italy , and the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2025, being held June 13 to 16 in Glasgow, United Kingdom . "Our presentations feature large patient populations from the PIONEER, PATHFINDER and EXPLORER trials, with follow-up reaching up to five years in ISM and up to 6.5 years in advanced SM, reflecting both the favorable long-term benefits of AYVAKIT and the unprecedented datasets we have amassed over time," said Becker Hewes , M.D., Chief Medical Officer at Blueprint Medicines . "AYVAKIT has shown transformative clinical outcomes for patients across the spectrum of SM, including sustained disease control in ISM and prolonged survival in advanced SM. These compelling results have translated into real-world practice, with clinicians expanding their view of who is an appropriate candidate for disease-modifying therapy after positive AYVAKIT experiences, and treatment durations trending toward multiple years." PIONEER Three-Year Data: Durable Clinical Benefits and Consistent Safety Profile with Long-Term AYVAKIT Use in ISM As previously presented,1 AYVAKIT demonstrated robust improvements through 144 weeks in overall symptom and symptom domain measures (skin, gastrointestinal, neurocognitive) representative of real-world patient impacts. AYVAKIT showed a well-tolerated safety profile and a low discontinuation rate due to treatment-related adverse events (TRAEs; 3 percent) with a median of three years of exposure, and some patients out to five years on therapy. Common TRAEs included low-grade edemas, headache and nausea. In newly reported data, AYVAKIT showed sustained clinical benefits across quality-of-life measures that reflect general health status and are broadly recognized by allergists/immunologists, validating previously presented results from the disease-specific, Mastocytosis Quality of Life (MC-QoL) questionnaire. This data presentation follows the May 2025 online publication of PIONEER two-year efficacy and safety data in The Journal of Allergy and Clinical Immunology : In Practice. PATHFINDER/EXPLORER Multi-Year Data: Long-Term Survival Benefits of AYVAKIT in Advanced SM AYVAKIT showed prolonged overall survival (OS) in PATHFINDER and EXPLORER, when indirectly compared to real-world data for midostaurin from the German Registry on Disorders of Eosinophils and Mast Cells (GREM). AYVAKIT led to meaningful survival benefits in patients across all prognostic categories (low, intermediate and high risk), per the Revised Mutation-Adjusted Risk Score (MARS-R) – a new OS risk assessment tool for advanced SM. Conducted in collaboration with University Hospital Mannheim, the analyses validate the MARS-R tool's ability to assess OS risks in advanced SM patients treated with AYVAKIT or midostaurin, using clinical and genetic parameters. The MARS-R was developed to inform physician care decisions based on individual patient needs. PRISM Data: Substantial Disease Burden Across Broad Population of Patients with ISM PRISM is one of the largest studies characterizing the impact of SM from both patient and clinical perspectives. Across the spectrum of disease severity, patients with ISM experienced physical, social and emotional challenges that caused meaningful disruption to their daily lives. Patients reported a broad constellation of disease-related impacts, including limitations to physical activities, work/college and relationships; problems with pain/discomfort and anxiety/depression; and adjustments in their daily lives to avoid certain foods, extended sun exposure and smells. Data Presentations EHA2025 Congress Oral Presentation: The Revised Mutation-Adjusted Risk Score (MARS-R) for Predicting Overall Survival in Patients with Advanced Systemic Mastocytosis Treated with Midostaurin or Avapritinib (Abstract S216) Poster Presentation: Blood-Based Proteomics for Deeper Insights Into Indolent Systemic Mastocytosis: The PIONEER Trial Experience (Abstract PS1838) Poster Presentation: High Accuracy of Peripheral Blood Testing Using Machine Learning–Derived Predictive Models to Distinguish Advanced from Indolent Systemic Mastocytosis: Analysis of Avapritinib and Elenestinib Trial Data (Abstract PF1310) Publication-Only Abstract: Phase 2/3 HARBOR Study of Elenestinib in ISM: A Trial-in-Progress Update of Novel Endpoints and Biomarkers Aimed at Evaluating Disease Modification (Abstract PB3108) EAACI Congress 2025 Flash Talk Presentation: Favorable Benefit-Risk Profile of Avapritinib in Indolent Systemic Mastocytosis Is Maintained After 3 Years of Therapy: Longer-Term Analysis of the PIONEER Study (Abstract 000621) Flash Talk Presentation: The Socio-Emotional Impact of Indolent Systemic Mastocytosis: Insights from the PRISM Survey (Abstract 000488) Poster Presentation: The Phase 2/3 Study of Elenestinib, a Highly Potent and Selective Tyrosine Kinase Inhibitor, in Patients with Indolent Systemic Mastocytosis (Abstract 001121) Data presentations are being made available in the "Science―Publications and Presentations" section of the company's website at 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). A broad range of symptoms, including anaphylaxis, maculopapular rash, pruritus, diarrhea, brain fog, fatigue and bone pain, frequently persist in patients with ISM 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. Until 2023, there were no approved therapies for the treatment of ISM. 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 and poor survival. About AYVAKIT AYVAKIT (avapritinib) is the first and only medicine approved by the U.S. Food and Drug Administration (FDA) to treat the root cause of SM. It was FDA approved for the treatment of advanced SM in June 2021 and ISM in May 2023. It now is indicated in adults with ISM, adults with advanced SM, including ASM, SM-AHN and MCL, and adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. The medicine is approved in the EU as AYVAKYT for the treatment of adults with ISM with moderate to severe symptoms inadequately controlled on symptomatic treatment, 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. The therapy is not recommended for the treatment of patients with low platelet counts (less than 50,000/µL). Globally, the medicine is approved for one or more indications in 16 countries, including China where it is marketed by CStone Pharmaceuticals, paying tiered percentage royalties on sales. 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. Important Safety Information Intracranial Hemorrhage — 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 clinical trials. 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. In ISM patients, no events of ICH occurred in the 246 patients who received any dose of AYVAKIT in the PIONEER study. Monitor patients closely for risk factors of ICH which may include history of vascular aneurysm, ICH or cerebrovascular accident within the prior year, concomitant use of anticoagulant drugs, or thrombocytopenia. Symptoms of ICH may include headache, nausea, vomiting, vision changes, or altered mental status. Advise patients to seek immediate medical attention for signs or symptoms of ICH. Permanently discontinue AYVAKIT if ICH of any grade occurs. In Advanced SM patients, 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 Effects — Cognitive adverse reactions can occur in patients receiving AYVAKIT and occurred in 33% of 995 patients overall in patients who received AYVAKIT in clinical trials including: 28% of 148 Advanced SM patients (3% were Grade ≥3), and 7.8% of patients with ISM who received AYVAKIT + best supportive care (BSC) versus 7.0% of patients who received placebo + BSC (<1% were Grade 3). Depending on the severity and indication, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue. Photosensitivity — AYVAKIT may cause photosensitivity reactions. In all patients treated with AYVAKIT in clinical trials (n=1049), photosensitivity reactions occurred in 2.5% of patients. Advise patients to limit direct ultraviolet exposure during treatment with AYVAKIT and for one week after discontinuation of treatment. Embryo-Fetal Toxicity — 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. Adverse Reactions — The most common adverse reactions (≥20%) in patients with Advanced SM were edema, diarrhea, nausea, and fatigue/asthenia. The most common adverse reactions (≥10%) in patients with ISM were eye edema, dizziness, peripheral edema, and flushing. Drug Interactions — Avoid coadministration of AYVAKIT with strong or moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided in patients with Advanced SM, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong or moderate CYP3A inducers. If contraception requires estrogen, limit ethinyl estradiol to ≤20 mcg unless a higher dose is necessary. To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. AYVAKIT is available in 25-mg, 50-mg, 100-mg and 200-mg tablets. Please click here to see the full U.S. Prescribing Information for AYVAKIT. About Blueprint Medicines Blueprint Medicines is a global, fully integrated biopharmaceutical company that invents life-changing medicines. We seek to alleviate human suffering by solving important medical problems in two core focus areas: allergy/inflammation and oncology/hematology. Our approach begins by targeting the root causes of disease, using deep scientific knowledge in our core focus areas and drug discovery expertise across multiple therapeutic modalities. We have a track record of success with two approved medicines, including AYVAKIT/AYVAKYT (avapritinib) which we are bringing to patients with SM in the U.S. and Europe. Leveraging our established research, development, and commercial capability and infrastructure, we aim to significantly scale our impact by advancing a broad pipeline of programs ranging from early science to advanced clinical trials in mast cell diseases and solid tumors. For more information, visit www.BlueprintMedicines.com and follow us on X (formerly 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 Blueprint Medicines' leadership role and its ability to transform treatment across the spectrum of SM, including sustained disease control in ISM and prolonged survival in advanced SM; AYVAKIT/AYVAKYT's position as the durable standard of care and clinicians' view of appropriate candidates and treatment duration; 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' strategy, goals, 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 Blueprint Medicines' ability and plans in continuing to build out 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 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 successfully expand its operations, research platform and portfolio of therapeutic candidates, and the timing and costs thereof; the success of Blueprint Medicines' current and future collaborations, financing arrangements, partnerships or licensing arrangements; and the ability of the parties to consummate the proposed merger between Blueprint Medicines and Sanofi on the timeline anticipated or at all, including the occurrence of any event, change or other circumstance that could give rise to the termination of the merger. 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 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. Footnote 1 Reported at the 2025 American Academy of Allergy, Asthma & Immunology (AAAAI) / World Allergy Organization (WAO) Joint Congress Trademarks Blueprint Medicines , AYVAKIT, AYVAKYT and associated logos are trademarks of Blueprint Medicines Corporation. 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小李，28岁，因腹胀加重半年就诊。最初他以为是吃得多导致的“发胖”，尝试节食后腹部却越发突出，同时伴有疲乏无力、反复腹泻。他的面色苍白，皮肤略显蜡黄。多次外院检查均未发现明确原因，被建议“调整饮食，多锻炼”。最终，小李到当地三甲医院血液科就诊。查体发现，他的脾脏显著肿大，触及肋缘以下6厘米，且胸骨轻叩有压痛。血液检测提示白细胞、血小板显著减少，骨髓穿刺显示肥大细胞显著增多。进一步基因检测发现KIT D816V突变，最终确诊为一种由肥大细胞异常增殖引起的罕见疾病：系统性肥大增多症（SM）。什么是SM？肥大细胞增多症是异常肥大细胞在一个或多个组织器官中浸润导致的一种罕见的异质性肿瘤。根据第五版世界卫生组织（WHO）分类标准，肥大细胞增多症可分为三个疾病亚型——皮肤型肥大细胞增多症（CM）、系统性肥大增多症（SM）和肥大细胞肉瘤（MCS）。系统性肥大增多症（SM）是侵袭性肥大细胞在真皮组织以外的一个或多个组织、器官或系统的克隆性增殖，并释放大量的血管活性介质，引起多器官功能障碍，常见的受累部位包括骨髓、皮肤、脾脏、淋巴结、肝脏和（或）单核-巨噬细胞系统，约占肥大细胞增多症的10%。临床表现包括全身症状、肥大细胞活化症状（介质导致的症状）、相关疾病症状以及体征：（1）全身症状：发热、疲劳、体重减轻、盗汗等。（2）肥大细胞活化症状：①过敏反应；②乏力；③眩晕、晕厥/昏迷；④皮肤：面部、颈部和胸部皮肤潮红，瘙痒伴或不伴皮疹，荨麻疹伴或不伴血管性水肿；⑤胃肠：胃部不适、腹泻、恶心、呕吐、腹痛、腹胀、胃食管反流病；⑥神经精神：头痛、脑雾、认知障碍、焦虑、抑郁、记忆力减退、注意力不集中；⑦心血管：心率快、胸痛、低血压、高血压、血压不稳定；⑧呼吸：喘息和气短；⑨骨骼肌肉：骨骼肌肉疼痛、骨质硬化、骨质减少、骨质疏松；⑩鼻喉：鼻痒、鼻塞、喉咙发痒和肿胀。（3）相关疾病症状：部分患者存在血液系统疾病相关症状。（4）体征：肝肿大、脾肿大和淋巴结肿大等。分型SM可分为骨髓肥大细胞增多症（BMM）、ISM、冒烟型系统性肥大细胞增多症（SSM）、ASM、SM-AHN和MCL六个亚型。诊断SM需满足主要标准和1项次要标准或同时满足≥3项次要标准。治疗系统性肥大增多症（SM）的治疗以缓解肥大细胞活化症状、降低疾病负担为目标，具体措施包括以下几方面：1.抗介质治疗： 避免诱因，局部应用润肤霜或色甘酸钠，严重症状时使用抗组胺药、抗白三烯药物或皮质类固醇激素。2.预防性治疗： 针对慢性介质相关症状可逐步应用酮替芬、H1和H2受体阻断药、白三烯受体拮抗剂及质子泵抑制剂等。严重患者可能需要奥马珠单抗或糖皮质激素。3.急性过敏反应的处理： 系统性荨麻疹或过敏性休克需立即肌注肾上腺素，并根据情况重复注射，必要时静脉给药。4.骨质疏松治疗： 可根据骨病严重程度使用双膦酸盐或其他骨代谢相关药物。5.传统治疗： 羟基脲和干扰素-α可用于控制症状和减少肥大细胞负担，克拉屈滨对严重病例疗效显著。6.靶向治疗： 小分子激酶抑制剂（如阿伐替尼、米哚妥林）通过抑制KIT突变改善病情，特别适用于晚期SM患者。异基因造血干细胞移植：对于进展型SM（AdvSM）患者，allo-HSCT是唯一潜在的治愈手段，但需严格评估适应症。参考资料：1.  中华医学会血液学分会实验诊断学组，中国肥大细胞增多症协作网络. 成人系统性肥大细胞增多症诊断与治疗中国指南（2022年版）. 中华血液学杂志，2022，43(12):969-978. DOI:10.3760/cma.j.issn.0253-2727.2022.12.0012.罗睿恒，王二华，李昕,等. 急性髓系白血病合并系统性肥大细胞增多症1例. 中国临床案例成果数据库，2022，04(01):E07211-E07211. DOI:10.3760/cma.j.cmcr.2022.e07211来源 | 梅斯医学编辑 | wanny神经系统罕见病交流群↓点击下方“阅读原文”，下载梅斯医学APP吧！