Midostaurin

-- ASH data reinforce survival benefits of front-line AYVAKIT® (avapritinib) use in patients with advanced SM -- -- Bone density analyses reported in patients with advanced SM underscore disease-modifying effects of AYVAKIT -- CAMBRIDGE, Mass., Dec. 7, 2024 /PRNewswire/ -- Blueprint Medicines Corporation (Nasdaq: BPMC) today announced data presentations that continue to demonstrate the long-term clinical benefits of AYVAKIT® (avapritinib) in advanced systemic mastocytosis (advanced SM), and reflect the company's ongoing partnership with the SM community to redefine the future of patient care – from improving diagnostic rates to raising the bar on treatment outcomes. The datasets, which include one oral presentation and three poster presentations, will be reported at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, taking place December 7-10 in San Diego. "Systemic mastocytosis is associated with mast cell infiltration across multiple organ systems, chronic inflammation caused by immune dysregulation, unpredictable symptoms that may worsen over time, and serious comorbidities such as osteoporosis, highlighting the urgency to treat patients early in the course of their disease," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "AYVAKIT has fundamentally changed the treatment paradigm by targeting the disease at its source, showing prolonged survival outcomes for patients with advanced SM, as well as durable symptom control and quality-of-life improvements for patients with ISM. Based on the substantial datasets we have amassed over more than a decade, and our continued collaboration with the SM community, we have designed the HARBOR trial of elenestinib – a next-generation KIT D816V inhibitor – to rigorously assess a broad range of endpoints reflecting disease-modifying impact." Data reported at ASH highlight the survival benefits of front-line AYVAKIT use in patients with advanced SM, and support Blueprint Medicines' plans to evaluate novel clinical measures indicative of disease modification – such as bone density and biomarkers of chronic inflammation – in the registrational HARBOR trial. Key results include: In pooled analyses from the PATHFINDER and EXPLORER trials, treatment-naïve patients with advanced SM showed significant survival benefits with AYVAKIT, when indirectly compared to real-world outcomes for midostaurin. In the PATHFINDER trial, AYVAKIT led to sustained improvements in bone density for advanced SM patients who had low bone mass at baseline. In the PIONEER trial, patients with indolent SM (ISM) had significant baseline levels of immune dysregulation relative to healthy donors, reflecting the chronic inflammatory burden of the disease. Non-Invasive, Blood-Based Assay Identified KIT Mutations Not Previously Detectable by Existing Tests ASH data show that ultra-sensitive KIT testing in the peripheral blood – a novel tool in clinical development that is more sensitive than current commercially available methods – identified previously undetected KIT mutations in a number of PIONEER trial patients. Emerging clinical research with ultra-sensitive KIT assays suggest SM may be more prevalent than previously thought. An additional data presentation highlights the application of machine learning techniques to analyze baseline, blood-based parameters of Blueprint Medicines' clinical trial participants. Following these analyses, a predictive model was developed to distinguish between advanced SM and ISM, and its accuracy was validated by an independent dataset from Dana-Farber Cancer Institute. Collectively, these data build on Blueprint Medicines' collaborative efforts with clinical experts to improve and accelerate how SM is diagnosed and treated. Data presentations will be made available in the "Science―Publications and Presentations" section of Blueprint Medicines' website. Oral Presentation: Analysis of Avapritinib Clinical Trial Data Generates a Highly Accurate Predictive Model for Advanced Systemic Mastocytosis Versus Indolent Systemic Mastocytosis Based on Peripheral Blood Testing (Abstract 107 – Saturday, December 7) Poster Presentation: Overall Survival and Duration of Treatment in Patients with Advanced Systemic Mastocytosis Receiving Avapritinib Versus Midostaurin or Best Available Therapy in a Real-World Setting (Abstract 1801 – Saturday, December 7) Poster Presentation: Ultra-Sensitive KIT Testing Uncovers Previously Undetected KIT Mutations in Patients with Indolent Systemic Mastocytosis: Results from the PIONEER Trial (Abstract 3164 – Sunday, December 8) Poster Presentation: Disease-Modifying Effects of Avapritinib in Patients with Advanced Systemic Mastocytosis: Improvements in Bone Density (Abstract 4544 – Monday, December 9) Publication-Only Abstract: Blood-Based Proteomics for Deeper Insights into Indolent Systemic Mastocytosis: the PIONEER Trial Experience (Abstract 6569) 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, pruritis, 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 (avapritinib) AYVAKIT (avapritinib) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of three indications: 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. Under the brand name AYVAKYT® (avapritinib), this medicine is approved by the European Commission for the treatment of adults with ISM with moderate to severe symptoms inadequately controlled on symptomatic treatment, adults with ASM, SM-AHN and 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). 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 . 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 systemic mastocytosis (SM) in the U.S. and Europe. Leveraging our established research, development, and commercial capability and infrastructure, we now 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 including SM and chronic urticaria, breast cancer and other solid tumors. For more information, visit 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 the potential benefits of AYVAKIT for the treatment of patients with advanced SM and ISM; statements regarding the HARBOR trial for elenestinib; plans, strategies, timelines 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," "opportunity," "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 delay of any current or planned clinical trials or the development of the company's current or future drug candidates; the company's 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 possibility that preclinical and clinical results for the company's 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 the possibility patient enrollment rates may be delayed or slower than anticipated; the actions of regulatory agencies and how this may affect the initiation, timing and progress of clinical trials; the company's 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 the company's current and future collaborations, 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 the company's 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, the company explicitly disclaims any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. 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● 三份最新报告展示三种DXd ADC在肺癌和乳腺癌领域的研究成果 ● “科技日”介绍第一三共研发管线数据和策略 　　新泽西州巴斯金里奇-（2024年12月3日）- 第一三共将在其科技日之前的2024年欧洲肿瘤内科学会（ESMO）亚洲大会（#ESMOAsia24）、圣安东尼奥乳腺癌研讨会（#SABCS24）和美国血液学学会（#ASH24）年会上，报告其肿瘤产品组合用于治疗多种实体瘤和血液瘤的最新研究成果，涉及超过45篇摘要。 　　ESMO亚洲大会、SABCS和ASH大会报告将展现第一三共在重塑肿瘤治疗新标准方面取得的进展。会议亮点包括ESMO Asia中的三项最新报告，包括datopotamab deruxtecan（Dato-DXd）治疗表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌（NSCLC）的2期研究TROPION-Lung05和3期研究TROPION-Lung01的汇总分析，以及SABCS报告的注射用德曲妥珠单抗（商品名：优赫得®，以下简称“T-DXd”）3期研究DESTINY-Breast06的亚组分析，治疗不可切除或转移性 HR阳性、HER2低表达（IHC 1+或 IHC 2+/ISH-）或HER2超低表达（IHC 0 伴膜染色）乳腺癌患者，以及patritumab deruxtecan（HER3-DXd）治疗早期HR阳性、HER2阴性乳腺癌患者的2期研究VALENTINE的初步结果。 Ken Takeshita 博士 第一三共全球研发负责人 　　在这些即将召开的会议，第一三共将重点介绍在难治性癌症方面的重要进展，包括肺癌、乳腺癌、胃癌、胆道癌以及急性髓系白血病（AML）和外周T细胞淋巴瘤。我们将持续推动获批药物和管线药物的重要研究进展，实现重塑癌症治疗新标准这一目标。 肺癌、乳腺癌、胃癌和胆道癌领域创新成果 亮相 ESMO 亚洲大会 　　ESMO亚洲大会上展示的最新数据将重点介绍Dato-DXd用于既往经治EGFR突变晚期NSCLC患者的一项汇总分析结果，涵盖2期研究TROPION-Lung05以及3期研究TROPION-Lung01。 　　两个小型口头报告包括Dato-DXd治疗既往经治HR阳性、HER2低表达或阴性乳腺癌的3期研究TROPION-Breast01中国患者的结果，以及T-DXd治疗既往经治HER2阳性晚期胃或胃食管结合部（GEJ）腺癌中国患者的2期研究DESTINY-Gastric06的最终结果。基于DESTINY-Gastric06的结果，T-DXd近期在中国获得附条件批准，即 T-DXd单药治疗既往接受过两种或两种以上治疗方案的局部晚期或转移性HER2阳性成人胃或胃食管结合部腺癌患者。 　　还将海报展示三项进行中T-DXd临床试验的研究设计，包括3期研究DESTINY-BTC01，该研究将在既往未接受过治疗的HER2表达、局部晚期或转移性胆道癌患者中评价T-DXd联合PD-1/TIGIT双特异性抗体rilvegostomig和标准治疗的疗效；1b/2期研究DESTINY-Gastric03，该研究新增队列以在HER2阳性或HER2低表达胃或胃食管结合部（GEJ）腺癌患者中评价T-DXd联合rilvegostomig和化疗的效果。T-DXd 2期研究DESTINY-PanTumor02的第2部分也将在会议上展示，该部分入组既往经治的HER2表达转移性实体瘤患者并分为五个队列：肿瘤表达HER2 IHC 3+的患者（不包括乳腺癌、胃癌和结直肠癌）；肿瘤表达HER2 IHC 2+/ISH+的患者（不包括乳腺癌、胃癌和结直肠癌）；HER2 IHC 2+/1+子宫内膜癌患者；HER2 IHC2+/1+卵巢癌患者；以及HER2 IHC 2+/1+宫颈癌患者。 　　　SABCS大会展示乳腺癌领域进展　　　 　　SABCS 将介绍乳腺癌领域的最新成果，包括两个口头报告：3 期研究 DESTINY-Breast06的亚组分析结果，即既往内分泌治疗对以下患者治疗结局的影响：接受T-DXd对比化疗的既往接受至少一线内分泌治疗失败的不可切除或转移性HR阳性、HER2低表达（IHC 1+或 IHC 2+/ISH-）或HER2超低表达（IHC 0 伴膜染色）乳腺癌患者，以及2期研究VALENTINE的主要结果，该研究在高风险HR阳性、HER2阴性早期乳腺癌患者中评价新辅助HER3-DXd单药或与来曲唑联合治疗。 　　会上报告的其他数据包括两份重点海报展示，突出介绍了3期研究DESTINY-Breast03的首次探索性生物标志物分析，该分析评估基因组改变对T-DXd与trastuzumab emtansine（T-DM1）相比治疗HER2阳性转移性乳腺癌患者疗效的影响，以及3b/4期研究DESTINY-Breast12中T-DXd对健康相关生活质量和神经功能的影响，该研究在既往经治HER2阳性、伴或不伴脑转移的转移性乳腺癌患者中进行。将以海报展示的形式报告1b期研究DESTINY-Breast08剂量扩展部分的最终结果，该研究在HER2低表达转移性乳腺癌患者中评价T-DXd与卡培他滨或capivasertib联合治疗。 　　进行中研究的海报将展示DXd ADC与valemetostat联合治疗的phase 1b master protocol trial中子方案A的研究设计，该子方案研究评价T-DXd与EZH1和EZH2双重抑制剂valemetostat联合治疗用于既往经治HER2低表达不可切除或转移性乳腺癌患者， 以及一项T-DXd与valemetostat联合治疗的phase 1b trial的研究设计，该研究在既往经治HER2低表达、HER2超低表达或HER2无表达转移性乳腺癌患者中评价联合给药的表现。 血液肿瘤产品治疗白血病和淋巴瘤的最新进展 　　在ASH年会上将介绍VANFLYTA®(Quizartinib)用于新诊断的FMS样酪氨酸激酶3-内部串联重复（FLT3-ITD）阳性 AML 患者的3期研究QuANTUM-First的多项子分析。其中，一项口头报告将重点分析该研究中患者共突变的频率及其对缓解率、总生存期和无复发生存期的影响。三份海报展示包括维持治疗对VANFLYTA疗效的影响，重点关注可测量残留病灶状态；临床研究检测方法对FLT3-ITD突变的检出与用下一代测序（NGS）检测可测量残留病灶之间的一致性；以及VANFLYTA与Midostaurin在新诊断的FLT3-ITD阳性AML患者中的匹配调整间接比较分析（MAIC）。 　　此外，还有海报展示一项VANFLYTA联合标准化疗治疗新诊断的FLT3-ITD阴性AML患者的2期研究QUIWI的最终结果，以及关于突变状态（包括FLT3-TKD和NPM1）和ELN风险分类的其他子分析。基于QUIWI研究结果的全球多中心随机对照研究QuANTUM-Wild，将进一步评价VANFLYTA联合标准化疗在此人群的疗效。QuANTUM-Wild的研究设计将作为正在进行中的研究（TIP）通过海报重点展示。 　　在ASH年会上还将展示其他两份海报数据，即一项评价Valemetostat在复发或难治性大B细胞淋巴瘤患者中的2期研究VALYM的主要结果；以及一项基于最近发表在The Lancet Oncology上的2期研究VALENTINE-PTCL01、针对循环肿瘤DNA（一种新型生物标志物）的探索性分析，以潜在预测Valemetostat在复发或难治性外周T细胞淋巴瘤患者中的临床疗效。 　　　　　　　　　科技日　　　　　　　　　 　　第一三共将于东部标准时间2024年12月16日星期一下午5:30至7:30/日本标准时间2024年12月17日星期二上午7:30至9:30举办投资者“科技日”（原“研发日”）活动。第一三共高管将介绍在ESMO亚洲、SABCS和ASH大会上展示的研究成果，以及研发战略。 ESMO亚洲大会、SABCS和ASH大会数据亮点 　　第一三共在2024年ESMO亚洲大会上展示的DXd ADC产品组合数据亮点包括： 　　第一三共在2024年SABCS上展示的DXd ADC产品组合数据亮点包括： 　　第一三共在2024年ASH年会上展示的血液学产品组合数据亮点包括： 　关于第一三共ADC产品组合　 　　第一三共的ADC产品组合包括7款目前处于临床开发阶段的ADC，这些ADC基于第一三共内部研发的两个不同的ADC技术平台。 　　目前临床开发进展最为领先的平台当属第一三共DXd AD技术平台，每AD由单克隆抗体通过可裂解四肽连接子与多个拓扑异构酶I抑制剂有效载荷（一种依喜替康衍生物，DXd）连接组成。DXd ADC产品组合目前包括靶向HER2的ADC T-DXd和靶向TROP2的ADC Dato-DXd，上述两款产品目前由第一三共与阿斯利康共同开发并在全球范围内商业化。HER3-DXd（靶向HER3的ADC）、ifinatamab deruxtecan（I-DXd，靶向 B7-H3 的ADC）、raludotatug deruxtecan（R-DXd，靶向CDH6的ADC）目前由第一三共与默沙东共同开发并在全球范围内商业化。DS-3939是一款靶向TAMUC1的ADC，目前由第一三共开发。 　　第一三共的第二个ADC平台由单克隆抗体与改良吡咯并苯并二氮杂卓 (PBD) 有效载荷连接组成。DS-9606是一款靶向CLDN6的PBD ADC，是计划利用该平台进行临床开发的几款ADC中的第一款。 　　Dato-DXd、I-DXd、HER3-DXd、R-DXd、DS-3939和DS-9606均为在研药物，尚未在任何国家/地区获批用于任何适应症。安全性和有效性尚未确定。             关于第一三共             　　第一三共是一家为社会可持续发展做贡献的创新型全球医疗保健公司，致力于发现、开发和提供新的标准疗法，以提高世界各地患者的生活质量。第一三共专注制药行业120余年，凭借其世界一流的科学和技术，为癌症、心血管疾病和其他医疗需求远未得到满足的疾病患者研发新的治疗方法和创新药物。如欲了解更多信息，请访问www.daiichisankyo.com。 声明: 1.本材料不用于任何推广目的，相关信息亦不应作为治疗或使用建议。如有相关问题请咨询医疗卫生专业人士。 2.本文涉及未在中国获批的产品或适应症，第一三共不推荐任何未获批药品/适应症的使用。