Revumenib

– Total revenue of $64.9 million in 1Q26, a 224% year-over-year increase – – Revuforj® (revumenib) net revenue of $48.9 million in 1Q26, highlighting leadership in menin inhibition and increasing uptake in R/R NPM1m AML – – Niktimvo™ (axatilimab-csfr) net revenue of $55.1 million in 1Q26, resulting in Syndax collaboration revenue of $15.9 million – – New revumenib real-world, frontline, and post-HSCT maintenance data anticipated in 2Q26 – – Topline data expected in 4Q26 from Phase 2 trials of axatilimab in IPF and newly diagnosed chronic GVHD – – Company to host a conference call today at 4:30 p.m. ET – NEW YORK , April 30, 2026 (GLOBE NEWSWIRE) -- Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company advancing innovative cancer therapies, today reported its financial results for the first quarter ended March 31, 2026 , and provided a business update. “We delivered over $100 million in combined Revuforj and Niktimvo net sales in the first quarter, highlighting strong demand for our medicines and advancing the company towards profitability. Revuforj net revenue totaled $49 million , underscoring our leadership in menin inhibition and strong adoption in both R/R NPM1m AML and KMT2Ar acute leukemia. Notably, recent analysis indicates that Revuforj is enabling nearly half of KMT2A patients to receive a stem cell transplant, providing the best chance for durable remission and positioning the franchise for long-term growth as an increasing number of patients return to therapy post-transplant,” said Michael A. Metzger , Chief Executive Officer. “We are poised for continued commercial growth with robust prescriber bases, excellent payer coverage, and multiple evolving treatment patterns that should extend the average duration of treatment for both medicines.” Mr. Metzger continued, “We are nearing multiple important catalysts this year, including new Revuforj data which will further highlight its best-in-class profile and topline data from Phase 2 trials of Niktimvo in frontline chronic GVHD and IPF. As we look ahead, we are focused on unlocking the multi-billion-dollar opportunities for our medicines and are well-positioned to be first to frontline AML with a menin inhibitor, with strong global site initiation and patient enrollment underway in our pivotal trials.” Recent Business Highlights and Anticipated Milestones Revuforj® (revumenib) Achieved $48.9 million in Revuforj net revenue in the first quarter of 2026, representing a 144% increase over the first quarter of 2025 and an 11% increase over the fourth quarter of 2025, driven primarily by increasing uptake in relapsed or refractory (R/R) NPM1 mutated (NPM1m) acute myeloid leukemia (AML). Total prescriptions increased by approximately 160% compared to the first quarter of 2025 and approximately 13% compared to the fourth quarter of 2025. Notably, recent analysis indicates that nearly half of R/R KMT2A translocated patients are proceeding to a hematopoietic stem cell transplant (HSCT) after receiving Revuforj, a significant increase from prior estimates of 33%. The Company expects this growing transplant rate to extend the average treatment duration as an increasing number of patients return to therapy after transplant. The Company expects the presentation of new revumenib data from multiple ongoing studies at major medical meetings throughout 2026.New/updated data expected in the second quarter of 2026: Findings from a multicenter real-world study. Post-HSCT maintenance data from multiple trials and centers. R/R NUP98r acute leukemia data from patients treated in the AUGMENT-101 trial or via an expanded access program. R/R data from the SAVE trial of revumenib in combination with venetoclax and decitabine/cedazuridine in NPM1m, KMT2Ar, and NUP98r acute leukemia. Frontline data from the Phase 1 trial of revumenib in combination with intensive chemotherapy in NPM1m, KMT2Ar, or NUP98r AML. New/updated data expected in the second half of 2026: Frontline data from the BEAT AML trial of revumenib in combination with venetoclax/azacitidine in NPM1m and KMT2Ar AML. R/R data from the Phase 1 trial of revumenib in combination with gilteritinib in AML patients with a FLT3 mutation and a KMT2A translocation, NPM1m, or any other mutation associated with HOX-MEIS1 overexpression. Multiple clinical trials evaluating revumenib across the acute leukemia treatment continuum are ongoing, such as: EVOLVE-2: A pivotal, Phase 3, randomized, double-blind, placebo-controlled trial of revumenib in combination with venetoclax and azacitidine in newly diagnosed NPM1m (primary efficacy analysis population) and KMT2Ar AML patients who are unfit for intensive chemotherapy. The trial is being conducted in collaboration with the HOVON network, a leading cooperative clinical trial group with extensive experience studying novel therapies for hematologic malignancies. REVEAL-ND: A pivotal, Phase 3, randomized, double-blind, placebo-controlled trial of revumenib in combination with intensive chemotherapy in newly diagnosed NPM1m AML patients. SAVE: A Phase 1/2 trial evaluating an all-oral combination of revumenib with venetoclax and decitabine/cedazuridine in pediatric and adult patients with newly diagnosed and R/R AML or mixed-lineage acute leukemia (MPAL) harboring either NPM1m, KMT2Ar, or NUP98r alterations. The trial is being conducted by investigators from MD Anderson Cancer Center. Intensive chemotherapy: Two ongoing Phase 1 trials evaluating the combination of revumenib with intensive chemotherapy (7+3) in newly diagnosed NPM1m or KMT2Ar acute leukemia patients. BEAT AML: A Phase 1 trial evaluating the combination of revumenib with venetoclax and azacitidine in newly diagnosed older adults (≥60 years) with NPM1m or KMT2Ar AML. The trial is being conducted as part of the Leukemia & Lymphoma Society's Beat AML® Master Clinical Trial. Post-transplant maintenance: A Phase 1 trial evaluating the safety and preliminary efficacy of revumenib as post-transplant maintenance after HSCT in patients with KMT2Ar or NPM1m acute leukemia. The trial is being conducted by investigators from the City of Hope Medical Center . Break Through Cancer: A Phase 2 trial studying whether the combination of revumenib and venetoclax can eliminate measurable residual disease (MRD) in patients with AML and extend progression-free survival. The trial is being conducted by Break Through Cancer, a collaboration between leading U.S. cancer research centers. INTERCEPT: A Phase 1 trial evaluating the use of novel therapies, including revumenib, to target MRD and early relapse in AML. The trial is being conducted by the Australasian Leukaemia and Lymphoma Group as part of the INTERCEPT AML master clinical trial. The Company expects the RAVEN trial to initiate in the second half of 2026. RAVEN is a Phase 2 collaborative trial of revumenib in combination with venetoclax and azacitidine in newly diagnosed KMT2Ar patients who would be considered eligible, or fit, for intensive chemotherapy. Niktimvo™ (axatilimab-csfr) Achieved $55.1 million in Niktimvo net revenue in the first quarter of 2026, representing significant growth compared to the $13.6 million in net revenue generated in the first quarter of 2025 from the first two months of the launch. Syndax and Incyte are co-commercializing Niktimvo. Syndax records 50% of the Niktimvo net commercial profit, defined as net product revenue minus the cost of sales and commercial expenses. Syndax’s share of the Niktimvo product contribution, reported as collaboration revenue, was $15.9 million in the first quarter of 2026. Presented data from nine axatilimab abstracts, including one oral presentation, at the Tandem Meetings (Transplantation & Cellular Therapy Meetings of ASTCT® and CIBMTR®) in February 2026 . The data presented included a comprehensive analysis of axatilimab in patients with chronic graft-versus-host disease (GVHD)-related bronchiolitis obliterans syndrome (BOS) in two clinical studies. The results show clinical and symptom responses across a spectrum of lung involvement. Two trials evaluating axatilimab in combination with standard of care therapies in newly diagnosed chronic GVHD patients are ongoing, including: A Phase 2, open-label, randomized, multicenter trial of axatilimab in combination with ruxolitinib in patients ≥ 12 years of age with newly diagnosed chronic GVHD. Topline data is now anticipated in the fourth quarter of 2026. A pivotal Phase 3, randomized, double-blind, placebo-controlled, multicenter trial of axatilimab in combination with corticosteroids in patients ≥ 12 years of age with newly diagnosed chronic GVHD. Topline data is anticipated in early 2028. Completed enrollment in MAXPIRe, a Phase 2, 26-week randomized, double-blinded, placebo-controlled trial of axatilimab on top of standard of care in patients with idiopathic pulmonary fibrosis (IPF) in the first quarter of 2026. The Company expects to report topline data in the fourth quarter of 2026. First Quarter 2026 Financial Results As of March 31, 2026 , Syndax had cash, cash equivalents, and short-term investments of $352.1 million and 88.8 million common shares and prefunded warrants outstanding. Total revenue for the first quarter of 2026 was $64.9 million , which consisted of $48.9 million in Revuforj net revenue and $15.9 million in Niktimvo collaboration revenue. The Niktimvo collaboration revenue is derived from the $55.1 million in Niktimvo net revenue that was previously reported by the Company's partner Incyte for the first quarter 2026. Syndax records 50% of the Niktimvo net commercial profit, defined as net revenue (recorded by Incyte) minus the cost of sales and commercial expenses. First quarter 2026 research and development expenses decreased to $58.8 million from $61.6 million for the comparable prior year period. The year-over-year decrease was primarily due to a decrease in Niktimvo related development milestone expense recognized in the first quarter of 2025, offset by an increase in Revuforj related clinical trial and personnel expenses. First quarter 2026 selling, general and administrative expenses decreased to $37.6 million from $41.0 million for the comparable prior year period. The year-over-year decrease was primarily due to a decrease in commercial-related expenses due to launch costs incurred in the first quarter of 2025 for Revuforj and Niktimvo that were not incurred in the same period in 2026 offset by a decrease in personnel expenses related to higher accrued compensation costs in 2025 for the achievement of corporate objectives. For the three months ended March 31, 2026 , Syndax reported a net loss attributable to common stockholders of $42.7 million , or $0.48 per share, compared to a net loss attributable to common stockholders of $84.8 million , or $0.98 per share, for the comparable prior year period. Financial Guidance For the full year of 2026, the Company expects total research and development plus selling, general and administrative expenses to be approximately $400 million , excluding the impact of $50 million in estimated non-cash stock compensation expense. Syndax expects that its operating expense base will remain stable over the next couple of years. As a result, Syndax expects that its cash, cash equivalents and short-term investments, combined with its anticipated product revenue, collaboration revenue and interest income, will enable the Company to reach profitability. Conference Call and Webcast In connection with the earnings release, Syndax's management team will host a conference call and live audio webcast at 4:30 p.m. ET today, April 30, 2026 . The live audio webcast and accompanying slides may be accessed through the Events & Presentations page in the Investors section of the Company's website. Alternatively, the conference call may be accessed through the following: Conference ID: Syndax1Q26 Domestic Dial -in Number: 800-590-8290International Dial-in Number: 240-690-8800Live webcast: https://sndx-1q26.open-exchange.net For those unable to participate in the conference call or webcast, a replay will be available on the Investors section of the Company's website at www.syndax.com approximately 24 hours after the conference call and will be available for 90 days following the call. About Revuforj® (revumenib) Revuforj (revumenib) is an oral, first-in-class menin inhibitor that is FDA approved for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation as determined by an FDA-authorized test in adult and pediatric patients one year and older. Revuforj is also indicated for the treatment of R/R acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 (NPM1) mutation in adult and pediatric patients one year and older who have no satisfactory alternative treatment options. Multiple trials of revumenib are ongoing or planned across the treatment landscape, including in combination with standard of care therapies in newly diagnosed patients with NPM1m or KMT2Ar AML. Revumenib was previously granted Orphan Drug Designation for the treatment of AML, ALL and acute leukemias of ambiguous lineage (ALAL) by the U.S. FDA and for the treatment of AML by the European Commission . The U.S. FDA also granted Fast Track designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation and Breakthrough Therapy Designation for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement. About Niktimvo™ (axatilimab-csfr) Niktimvo (axatilimab-csfr) is a first-in-class colony stimulating factor-1 receptor (CSF-1R)-blocking antibody approved for use in the U.S. for the treatment of chronic graft-versus-host disease (GVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg (88.2 lbs). In 2016, Syndax licensed exclusive worldwide rights to develop and commercialize axatilimab from UCB. In September 2021 , Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for axatilimab in chronic GVHD and any future indications. Axatilimab is being studied in frontline combination trials in chronic GVHD, including a Phase 2 combination trial with ruxolitinib (NCT06388564) and a Phase 3 combination trial with steroids (NCT06585774). Axatilimab is also being studied in an ongoing Phase 2 trial in patients with idiopathic pulmonary fibrosis (NCT06132256). About Syndax Syndax Pharmaceuticals is a commercial-stage biopharmaceutical company advancing innovative cancer therapies. Highlights of the Company's pipeline include Revuforj® (revumenib), an FDA-approved menin inhibitor, and Niktimvo™ (axatilimab-csfr), an FDA-approved monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. Fueled by our commitment to reimagining cancer care, Syndax is working to unlock the full potential of its pipeline and is conducting several clinical trials across the continuum of treatment. For more information, please visit www.syndax.com/ or follow the Company on X and LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "anticipate," "believe," "could," "estimate," "expects," "intend," "may," "plan," "potential," "predict," "project," "should," "will," "would" or the negative or plural of those terms, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Syndax's expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the progress, timing, clinical development and scope of clinical trials, the reporting of clinical data for Syndax's product candidates, the acceptance of Syndax and its partners' products in the marketplace, sales, marketing, manufacturing and distribution requirements, the potential use of its product candidates to treat various cancer indications and fibrotic diseases, and Syndax's expected full year total operating expenses, including its estimated non-cash stock compensation expense. Many factors may cause differences between current expectations and actual results, including: unexpected safety or efficacy data observed during preclinical or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes to Revuforj's or Niktimvo’s commercial availability; changes in expected or existing competition; changes in the regulatory environment; failure of Syndax's collaborators to support or advance collaborations or product candidates; and unexpected litigation or other disputes. Other factors that may cause Syndax's actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Syndax's filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein. Except as required by law, Syndax assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. Niktimvo is a trademark of Incyte.All other trademarks are the property of their respective owners. Syndax Contact Sharon Klahre Syndax Pharmaceuticals, Inc. sklahre@syndax.com Tel 781.684.9827 SNDX-G Source: Syndax Pharmaceuticals, Inc.

破晓时分：行业的的春日回响 2026年4月，全球肿瘤学界与血液病学界再次聚焦于精准医疗带来的深刻变革。 各大国际权威医疗咨询机构的数据正在印证一个全新的行业风口：根据Strategic Market Research发布的最新报告，随着急性白血病靶向药物的接连突破，Menin抑制剂的全球市场规模正以8.9%的复合年增长率迅速扩张，预计将从2024年的5.2亿美元飙升至2030年的8.72亿美元。 与此同时，为了弥合新药在不同国家间的可及性鸿沟，世界孤儿药联盟（WODA）正在全球范围内加速推进一项管理准入项目，旨在将最新的白血病靶向药物引入亚洲、拉美、中东等尚未正式获批的地区，为亟待救治的患者提供生命通道。 世界孤儿药联盟LOGO 图源stabiopharma.com 这一切热潮的源头，可以追溯到几个月前那场震撼血液病学界的“极速审批”。在现代肿瘤学的历史长河中，新药的研发与监管审批通常遵循着漫长而审慎的节奏，鲜少在同一细分领域出现密集的爆发。然而，2025年的深秋，急性髓系白血病（AML）领域却迎来了一场罕见的生机。 2025年10月24日，美国食品药品监督管理局（FDA）正式批准了首个口服Menin抑制剂revumenib（商品名Revuforj），用于治疗携带易感核磷蛋白1（NPM1）突变的复发或难治性急。 仅仅20天后的11月13日，另一款同类靶向药物ziftomenib（商品名Komzifti）也获得了FDA的全面批准，适应症同样直指携带NPM1突变的复发或难治性成人AML患者。 短短20天内，针对同一种白血病、同一个特定基因突变，连续有两款全新机制的靶向药物跨越监管门槛，走向临床一线。这种在时间线上极度密集的获批，其最迷人的吸引力在于，宏大的“精准医学”概念终于在白血病领域具体到了一个微观的分子错误上。 过去，医学界对待白血病常常是一整类疾病用一套化疗方案一起对付；而现在，某一个特定基因的异常，都有了为其量身定制的专属解药。 漫长暗夜 传统化疗的无差别攻击与 NPM1 的残酷悖论 要理解这20天奇迹背后的分量，必须把目光投向过去近半个世纪的白血病治疗史。自20世纪70年代以来，急性髓系白血病的标准诱导治疗几乎完全依赖于著名的“7+3”化学治疗方案。这套方案要求患者连续7天静脉输注阿糖胞苷，配合连续3天的蒽环类药物（如柔红霉素或伊达比星）。 阿糖胞苷结构式 图源Wikimedia Commons 这种无差别攻击的化疗模式，其核心逻辑是“玉石俱焚”，试图通过摧毁整个骨髓造血系统来换取恶性克隆的消亡。对于年轻且体质较好的患者，这种方式确实能带来一定的缓解率。但白血病往往好发于老年人，中位确诊年龄接近68岁 。对于年老体弱的患者而言，强烈的化疗往往意味着难以承受的毒副作用，包括严重的感染、出血和器官衰竭。 随着分子诊断技术的飞速发展，血液病学家逐渐意识到，急性髓系白血病并非一种单一的疾病，而是由数十种不同基因突变驱动的异质性症候群。在这其中，NPM1突变是成人AML中最常见的基因异常，约占所有成人病例的30% 。 在疾病初期，携带NPM1突变的患者如果接受传统的“7+3”标准化疗，往往表现出较高的完全缓解率（高达80%左右），因此在过去的风险分层中，单纯的NPM1突变一度被归类为预后良好的亚型。然而，这只是一个残酷的医学悖论。现实情况是，近半数携带该突变的患者会在一年内复发。 一旦疾病复发，或者对初始的诱导化疗产生耐药，传统的挽救性治疗手段便显得捉襟见肘。历史数据显示，在没有靶向治疗的时代，复发或难治性NPM1突变AML患者的生存前景极为黯淡，中位总生存期仅为6.1个月左右，长期生存率不足10%。 即使后来出现了维奈克拉（venetoclax）等BCL-2抑制剂，一旦患者在维奈克拉治疗后再次复发，医学界几乎面临无药可用的绝境。正是在这样一种绝望的临床空白中，科学家们开始在更微观的表观遗传学层面寻找破局的钥匙。 维奈克拉片 图源miaoshou.com 剥丝抽茧：破解致病程序 医学界对靶向药物的探索，始于对致病机制的理解。NPM1突变究竟在细胞深处引发了怎样的灾难？ 01 正常情况下，NPM1基因编码的核磷蛋白主要安分地待在细胞核的核仁中，负责核糖体的组装以及维持基因组的稳定性。 02 当NPM1发生突变后，这种蛋白质的结构发生了改变，导致它被异常地驱逐到了细胞质中。 这种看似简单的空间位置转移，却在细胞核内引发了一场灾难性的多米诺骨牌效应。核内调控机制的失衡，最终导致了HOXA9和MEIS1等一组关键转录因子的过度表达。你可以把这些基因的异常活跃，想象成给细胞植入了一套错误的“软件程序”。 这套程序使得本该正常发育成白细胞的幼稚髓系干细胞停止了成熟，转而开始无休止地疯狂自我复制。骨髓很快被这些毫无免疫功能的白血病母细胞填满，进而导致患者出现致命的贫血、感染和出血。 在这个错误的基因表达程序中，Dana-Farber癌症研究所的Scott Armstrong博士及其团队发现了一个至关重要的“同谋”——Menin蛋白。Menin本身并不是坏人，它是一个脚手架蛋白。 但在携带NPM1突变或KMT2A重排的白血病细胞中，HOXA9等促癌基因的持续表达，高度依赖于Menin蛋白与KMT2A（也被称为MLL1）蛋白复合物之间的紧密结合。如果没有Menin提供支架支撑，这套导致细胞无限增殖的错误程序就无法运转。 这一发现为新药研发指明了极其精确的靶点。Revumenib和ziftomenib正是基于这一原理诞生的小分子Menin抑制剂。它们的作用机制完全颠覆了传统化疗“毒杀一切快速分裂细胞”的粗暴逻辑。这两种药物就像是两把极其精密的分子钥匙，精准地楔入Menin与KMT2A蛋白之间的结合界面，强行拆散这对致病搭档。 当这对蛋白复合物被瓦解后，那套导致细胞无限增殖的致病程序就被强制关闭了。随之而来的是一种堪称温柔的医学奇迹：那些原本在骨髓中疯狂肆虐的白血病母细胞，在被阻断了促癌信号后，不再继续分裂，而是重新启动了被搁置的发育程序。 它们开始逐渐分化，最终成熟为具有正常形态和功能的健康中性粒细胞。这种不以杀戮为目的，而是将恶性细胞“改邪归正”的治疗理念，代表了肿瘤治疗从“物理性杀灭”向“表观遗传学纠偏”的深刻跨越。 中性粒细胞图 图源Wikimedia Commons 双峰并峙：详实的临床数据与重燃的生存希望 理论的推演最终必须接受临床实践的检验。在2025年，revumenib和ziftomenib分别通过两项具有里程碑意义的临床试验，向FDA和全球医学界交出了令人瞩目的答卷。这两款药物虽然在分子结构和部分药代动力学特性上存在差异，但在针对NPM1突变AML的疗效上却展现出了惊人的“殊途同归”。 01 首先是revumenib。其获批主要基于一项名为AUGMENT-101的1期/2期多中心临床试验。 权威医学期刊《血液》（Blood）发表了该试验针对NPM1突变队列的最终数据。这项研究纳入了64名极度难治的成年复发性NPM1突变AML患者。这组患者的病情极为棘手，超过三分之一的人此前已经接受过至少三线以上的治疗，75%的患者曾接受过维奈克拉治疗并产生耐药，甚至有22%的患者经历过造血干细胞移植失败。 在这样一群几乎耗尽所有治疗选项的患者中，revumenib单药治疗取得了46.9%的总体客观缓解率（ORR）。更为关键的是，有23.4%的患者达到了完全缓解（CR）或伴部分血液学恢复的完全缓解（CRh），中位缓解持续时间为4.7个月。 Revumenib药物图 图源revuforj.com 美国埃默里大学Winship癌症研究所的Martha Arellano教授和纪念斯隆-凯特琳癌症中心的Eytan Stein博士在解读数据时指出，在这部分达到深度缓解的患者中，有64%实现了微小残留病（MRD）阴性。 这意味着在分子层面上，药物已经将白血病细胞清扫到了常规检测无法发现的极低水平 。最令人振奋的是，有16.7%的应答患者在达到缓解后，成功获得了再次进行异基因造血干细胞移植的机会，从而赢得了潜在治愈的可能。对于那些达到完全缓解的患者，其中位总生存期跃升至23.3个月，远超历史对照数据。 02 几乎在同一时间，《临床肿瘤学杂志》（JCO）公布了ziftomenib的关键注册性临床试验KOMET-001的详实结果。 该研究在北美和欧洲招募了92名复发/难治性NPM1突变AML患者，他们每天仅需口服一次600mg的ziftomenib单药。研究结果显示，完全缓解及伴部分血液学恢复的完全缓解（CR/CRh）率达到了21.4%（文献中也常表述为22%）。 该研究的首席研究者、罗斯威尔帕克综合癌症中心白血病服务部主任Eunice Wang教授对这一结果给予了高度评价。她指出，ziftomenib不仅带来了深度的临床缓解，而且在那些获得CR/CRh的患者中，高达67%的人达到了MRD阴性状态。 在生存期方面，该药物使得整体队列的中位总生存期达到了6.6个月，而在产生应答的患者群体中，中位总生存期更是大幅延长至18.4个月。此外，研究还观察到患者对输血的依赖度显著降低，约20%的患者在治疗期间摆脱了红细胞或血小板的输注需求，极大地改善了生活质量。 这两种药物在20天的间隔内接连获批，绝非监管机构的偶然之举。在过去，这些经历了多次复发的终末期患者只能接受以减轻痛苦为目的的姑息治疗。而现在，Menin抑制剂为他们重新打通了通往造血干细胞移植的生命通道。 刀尖起舞：医学的人文关怀与特异性毒性管理 尽管靶向表观遗传学的Menin抑制剂在疗效上展现出了极高的精准度，成功避免了传统化疗引发的严重脱发、大面积黏膜炎和长时间的严重骨髓抑制，但这种特殊的机制也带来了全新的不良反应挑战。在真实的临床实践中，如何温柔且克制地管理这些毒性，考验着每一位血液科医生的智慧。 最引人注目的特异性不良反应被称为“分化综合征”（Differentiation Syndrome）。从某种意义上说，这种综合征的出现正是药物正在发挥作用的证明。 如前所述，Menin抑制剂促使大量停滞在幼稚阶段的白血病母细胞迅速启动分化程序，成熟为中性粒细胞。然而，在这一剧烈的集体“成熟”过程中，大量细胞会同时释放出极其丰富的炎性细胞因子。 这会导致患者出现不明原因的发热、呼吸急促、体重急剧增加、肺部浸润以及胸腔或心包积液等类似全身严重炎症的症状。  造血干细胞分化图 图源Wikimedia commons 在临床试验中，不论是revumenib还是ziftomenib，分化综合征的发生率都在15%到25%左右。面对这种如同在刀尖上起舞的并发症，FDA在批准这两款药物时都加上了关于分化综合征的黑框警告。 幸运的是，医学界已经建立了一套行之有效的临床干预预案。医生需要对患者进行极其密切的监测，一旦在用药后的前几个周期发现早期迹象，便会果断介入地塞米松等类固醇激素，必要时辅以羟基脲来控制白细胞的过度飙升。 只要发现及时并妥善处理，绝大多数分化综合征都是可控的，能够在保障患者生命安全的前提下，让药物继续完成对恶性细胞的表观遗传学改造。 此外，心脏毒性与药物相互作用也是这一类药物需要重点考量的因素。 在revumenib的临床试验中，心电图QTc间期延长成为了一个明显的剂量限制性毒性，有超过20%的患者出现了三级或以上的QTc延长，并且它会受到体内CYP3A4代谢酶强抑制剂的显著影响。 这要求临床医生在开具处方前，必须对患者正在使用的抗真菌药或抗生素等药物进行严格的筛查，并根据患者体重和合并用药情况随时调整revumenib的剂量。 相比之下，ziftomenib在分子设计上优化了这一局限。临床数据显示，ziftomenib缺乏临床意义上的严重QTc延长问题，且不存在显著的药物相互作用。 正如Kura Oncology公司的首席执行官Troy Wilson博士所言，ziftomenib由于没有QTc延长的黑框警告，并且采用每日一次的口服给药方式，为那些合并有多种基础疾病、需要同时服用多种药物的老年患者提供了一个更为宽容且易于管理的治疗选择。 东方破晓：中国血液学界的同频共振与本土探索 科学进步从来没有国界。在Menin抑制剂这股精准医疗的浪潮席卷全球之际，中国血液病学界并未缺席，而是以前所未有的速度与国际前沿保持着同频共振。 随着相关药物在海外的获批，国内外权威指南的更新几乎是瞬时完成的。美国国家综合癌症网络（NCCN）迅速行动，将ziftomenib和revumenib同时纳入了2026版急性髓系白血病临床实践指南，作为携带NPM1突变的复发/难治性患者的优选靶向疗法。 同样，中国临床肿瘤学会（CSCO）及中华医学会血液学分会的专家们也高度关注这一领域的颠覆性突破。哈尔滨血液病肿瘤研究所的马军教授等国内顶尖专家多次强调，分子靶向治疗正在重塑白血病的治疗格局，而针对特异性基因突变的检测已经成为初诊和复发患者的“必修课” 。中国血液学指南也在加速迭代，以期尽早将这些挽救生命的最新进展纳入规范化诊疗路径。 除了在临床指南上的接轨，中国在Menin抑制剂的本土创新与临床开发方面也展现出了强劲的科研实力。 中国医学科学院血液病医院的王建祥教授和魏辉教授牵头，已经启动了由和黄医药自主研发的创新Menin抑制剂HMPL-506的1期临床试验（NCT06387082）。该试验旨在评估这款本土原研药物在中国血液恶性肿瘤患者中的安全性、药代动力学特征与初步疗效。 与此同时，强生公司旗下的bleximenib（JNJ-75276617）以及国内多家创新药企的同类候选药物，也正在国内各大临床研究中心如火如荼地开展多中心临床测试。 这标志着中国患者未来不仅能够受惠于进口药物，更有望用上本土研发的平价替代方案。 乘胜追击：从终末期挽救到一线治愈的战略前移 尽管2025年10月和11月的两次获批仅仅是针对复发或难治性患者的单药治疗，但这绝非Menin抑制剂临床价值的终点，而是一个辉煌的起点。在血液病专家的宏大构想中，单药治疗虽然能带来可观的缓解，但中位缓解持续时间通常在五个月左右。研究表明，部分患者随后会因为MEN1基因产生继发性突变，改变了蛋白的结合位点，从而再次对药物产生耐药。 为了打破这一耐药魔咒，将短期的临床缓解转化为长期的彻底治愈，整个研发战线正在发生战略性的前移。目前，国际上多项备受瞩目的临床试验正试图将Menin抑制剂推向疾病的“一线战场”，并与现有的标准疗法进行强强联合。 在近期的国际会议上，研究人员公布了SAVE试验和KOMET-007试验的初步数据。这些试验大胆地将Menin抑制剂（分别与revumenib和ziftomenib）联合低强度化疗药物（如阿扎胞苷）和BCL-2抑制剂（维奈克拉），用于初诊的不适合强效化疗的老年NPM1突变AML患者。 初步的数据令人极度振奋：这种三药联合方案不仅极大地降低了分化综合征的严重程度，还将整体客观缓解率一举推高至80%到90%以上，绝大多数获得完全缓解的患者同时达到了MRD阴性的深层缓解状态。 对于那些能够耐受高强度化疗的年轻患者，Menin抑制剂与传统“7+3”方案的联合研究也在全速推进中，试图从根本上改写这部分患者的长期生存曲线。 从一类疾病的“狂轰滥炸”，到精确制导至一个具体基因突变的“分子纠偏”；从20天内接连问世的两种新药，到全球医学界为提高患者生存质量而进行的联合用药探索。这背后，是无数基础科学家数十年如一日的案头钻研，是临床医生在病床前与死神锱铢必较的坚持，也是现代制药工业在高度风险中不断投入的巨大勇气。 对于携带NPM1突变的急性髓系白血病患者而言，2025年末到2026年春的这段时间，无疑是一个历史性的转折点。它宣告了一个时代的结束，在这个时代里，白血病的复发往往意味着无可挽回的绝境；它也拉开了一个新纪元的帷幕，在这个纪元里，精准医学不再是停留在学术论文上的冰冷理论，而是化作了患者手中真真切切的口服药瓶。  分享，关注，点赞，一同愈见治愈的期盼