Fostamatinib Disodium

2026.4.22 2026年4月21日，由CDE官网公示，和黄医药自主研发的醋酸索乐匹尼布片（HMPL-523）提交了又一新适应症的上市申请，推测适应症或为既往至少对糖皮质激素治疗反应不佳的成人温抗体型自身免疫性溶血性贫血（wAIHA）。 图片来源：CDE官网 据悉，这是该药继免疫性血小板减少症（ITP）后，该药冲刺的第二项上市适应症，标志着这款高选择性Syk抑制剂在自身免疫性血液疾病领域的布局再进一步，也为长期缺乏精准靶向方案的wAIHA患者带来全新治疗曙光。 wAIHA治疗：传统方案困境重重，未被满足的临床需求迫切 所谓自身免疫性溶血性贫血（AIHA），即由于免疫系统紊乱产生抗自身红细胞抗体，导致红细胞被过度破坏引发的罕见溶血性疾病，温抗体型（wAIHA）占比超 70%，以慢性、复发性为核心特征，患者长期受重度贫血、疲劳、黄疸等困扰，严重者可出现溶血危象、重要脏器损伤，甚至危及生命。 而针对该疾病，当前临床治疗格局呈现“一线依赖激素、后线选择匮乏”的窘境，整体疗效与安全性存在显著短板： 一线治疗：糖皮质激素是wAIHA绝对一线方案，但仅约50%-60%患者初始应答，且存在完全缓解率低、复发率高等弊端，长期使用会引发骨质疏松、糖尿病、感染、胃肠道损伤等严重不良反应。而利妥昔单抗等生物制剂则多作为激素联合或失败后选择，但整体应答率不高。 二线及后线：环磷酰胺、硫唑嘌呤等免疫抑制剂的应用较为常见，但疗法存在骨髓抑制、肝肾功能损伤等显著副作用，患者耐受性差，缺乏精准靶向制剂。 而随着疾病作用机制与医学基础研究水平的上涨，近年来，如补体抑制剂（如苏特利单抗）、FcRn抑制剂（如Efgartigimod）等创新疗法确实逐步进入临床，但整体疗法局限性仍相对明显。 整体而言，wAIHA后线治疗长期缺乏机制创新、疗效确切、口服便捷的靶向药物，未满足需求极为迫切。 Syk抑制剂：AIHA治疗新机制，精准阻断溶血核心通路 Syk（脾酪氨酸激酶）是Fc受体与B细胞受体信号通路的关键枢纽激酶，在wAIHA发病中扮演核心角色：自身抗体结合红细胞后，通过Fcγ受体激活巨噬细胞内Syk信号通路，启动红细胞吞噬破坏。 同时Syk可促进B细胞活化与自身抗体持续产生，形成“溶血 - 抗体增多 - 再溶血”的恶性循环。 Syk抑制剂通过特异性阻断Syk激酶活性，双重干预疾病进程： 一方面抑制巨噬细胞吞噬功能，减少红细胞破坏。 另一方面抑制B细胞活化，降低自身抗体生成，从源头阻断溶血发生。 这一机制完全区别于传统激素、单抗及补体抑制剂，为wAIHA提供了全新的精准治疗路径。 竞争：全球仅两款核心药物，索乐匹尼布差异化优势显著 当前全球Syk抑制剂研发聚焦自身免疫性血液疾病，疗法整体需求差异化的竞争格局，醋酸索乐匹尼布凭借机制、疗效、安全性及便利性，形成明确优势。 据药智数据显示，福坦替尼（Fostamatinib，Rigel/拜耳）作为全球首款获批Syk抑制剂，2018年获FDA批准用于ITP，时至今日，该药仍是目前唯一上市的Syk抑制剂。但该药存在激酶选择性较差、脱靶毒性明显的问题，临床常见腹泻、恶心、高血压、肝酶升高等不良反应，患者长期依从性不佳；且针对wAIHA的临床研究进展缓慢，尚未提交相关适应症上市申请。 而醋酸索乐匹尼布作为中国首款、全球第二款冲刺上市的高选择性Syk抑制剂，研发代号HMPL-523。除本次申报的wAIHA外，其针对ITP的上市申请已于更早之前成功提交。 对于索乐匹尼布的核心优势而言，其不仅具备高选择性，安全性更优药物分子经精准优化，对Syk激酶选择性显著高于福坦替尼，脱靶效应极低。临床数据显示，其治疗相关不良事件多为轻度至中度，胃肠道毒性、高血压等发生率远低于福坦替尼，长期治疗耐受性良好。 wAIHA疗效确切，快速持久改善贫血Ⅱ期临床研究显示，索乐匹尼布治疗wAIHA总体血液学反应率达67%，持续血液学反应率为48%；治疗24周时，患者血红蛋白较基线平均提升29.5g/L，且呈持续上升趋势，显著改善贫血症状。2026年1月公布的Ⅲ期ESLIM-02研究顶线结果显示，试验达到主要终点，进一步验证其在wAIHA人群的稳健疗效。 小结 随着本次申报纳入优先审评，醋酸索乐匹尼布有望加速获批上市。 未来，随着ITP与wAIHA两大适应症相继落地，这款高选择性Syk抑制剂将逐步成为自身免疫性血液疾病后线治疗的核心选择，切实解决患者未被满足的临床需求，开启 AIHA精准治疗的全新时代。 扫描二维码 更多行业前沿分享 博腾股份成立于2005年，主要为全球药企、生物科技公司、科研机构等提供从临床前研究到药品上市全生命周期所需的小分子药物、多肽与寡核苷酸药物、蛋白与偶联药物以及细胞与基因治疗药物等一站式服务解决方案，研发、生产、运营场地覆盖中国（重庆、上海、四川、江苏、江西、湖北）、美国、斯洛文尼亚、比利时、瑞士和丹麦等地。我们始终坚持以客户为中心，致力于为客户提供创新、可靠的全球化、端到端CDMO服务，让好药更早惠及大众。 免责声明：文中系整合内容，观点不代表博腾及其所属子公司立场，亦不对本文所提供信息做任何形式的保证。同时，本文不做治疗方案推荐，也不承担因使用或依赖本文信息所产生的任何直接或间接的后果。如需获得治疗方案指导，请前往正规医院就诊。

Researchers at University Hospital Erlangen in Erlangen, Germany report that a single infusion of CD19 CAR-T therapy in autoimmune hemolytic anemia produced sustained remission in a patient with overlapping refractory AIHA, immune thrombocytopenia, and antiphospholipid syndrome, according to a study published April 10, 2026 in Med. The patient had failed nine prior treatment lines, including three courses of rituximab. The case involved a 47-year-old woman with concurrent cold- and warm-agglutinin autoimmune hemolytic anemia, ITP, and antiphospholipid antibody syndrome — a combination of autoantibody-driven disorders sharing a common pathogenic mechanism in dysregulated B cells. Prior therapies including steroids, intravenous immunoglobulin, azathioprine, bortezomib, and repeated rituximab had each failed to produce durable control. The treating team at Erlangen administered zorpocabtagene-autoleucel (Zorpo-cel; MB-CART19.1), an autologous 4-1BB-costimulated CD19-directed CAR-T cell product manufactured on the Miltenyi Prodigy platform, at a dose of 1 × 10⁶ CAR-positive T cells per kilogram following lymphodepletion with fludarabine and cyclophosphamide. Hematologic recovery was rapid. The patient achieved transfusion independence by day 7 and hemoglobin normalization above 12 g/dL by day 25. Hemolysis markers including LDH and haptoglobin normalized, and reticulocyte counts stabilized. Warm-reactive autoantibodies became undetectable, cold agglutinin titers fell, and antiphospholipid antibodies declined. Platelet counts improved without additional ITP-directed therapy. These responses were maintained across the 11-month follow-up period. The direct antiglobulin test showed conversion, and CAR-T cells demonstrated in vivo expansion detectable in peripheral blood following infusion. At approximately day 322, reconstituted B cells were 98% naïve phenotype, indicating that the reconstituting immune compartment lacked the autoreactive memory imprinting present before treatment. The safety profile was consistent with CAR-T cell therapy autoimmune hemolytic anemia experience in oncology settings. The patient developed Grade 1–2 cytokine release syndrome managed with tocilizumab and supportive care. No immune effector cell-associated neurotoxicity syndrome was observed. Hypogammaglobulinemia, an expected consequence of B cell depletion, was managed with immunoglobulin replacement. No treatment-related mortality or life-threatening infections occurred. The biological rationale for CD19-directed CAR-T cells in this setting centers on the shared dependence of AIHA, ITP, and antiphospholipid syndrome on autoreactive B cells producing pathogenic autoantibodies. CD19 is expressed across the B cell lineage, including on subsets and in tissue compartments where the anti-CD20 monoclonal antibody rituximab achieves incomplete penetration. The Erlangen authors note that CAR-T cells achieved remission despite three prior rituximab failures, consistent with the hypothesis that deeper and more anatomically complete B cell depletion — including in lymph nodes and mucosal compartments — underlies the more durable response. The 4-1BB costimulatory domain incorporated into Zorpo-cel is associated with enhanced CAR-T cell persistence and memory differentiation, which may contribute to the duration of response observed. The authors describe the qualitative change in the reconstituted B cell compartment as a key mechanistic finding. The near-complete naïve phenotype of returning B cells at day 322 suggests that pathogenic memory clones were eliminated and that immune reconstitution proceeded from progenitors without the autoimmune programming that had driven disease. The authors characterize this as a B cell reset rather than simple depletion, distinguishing the approach from conventional immunosuppression, which does not eliminate autoreactive memory. The Erlangen group has previously reported CD19 CAR-T outcomes in systemic lupus erythematosus, inflammatory myositis, and systemic sclerosis, establishing the broader concept of CAR-T-mediated immune reset in connective tissue diseases. The current report extends that work to autoimmune cytopenias — a distinct disease category where dedicated CAR-T data remain limited. Refractory AIHA treatment options after rituximab failure are constrained. Fostamatinib, a spleen tyrosine kinase inhibitor, carries regulatory approval for warm AIHA but does not address the underlying autoantibody mechanism. Sutimlimab targets complement component C1s and is approved specifically for cold agglutinin disease but does not eliminate pathogenic B cells. Thrombopoietin receptor agonists for ITP and anticoagulation for antiphospholipid syndrome address downstream consequences without modifying the autoimmune source. In the commercial CAR-T space, Kyverna Therapeutics is advancing KYV-101, a CD19-directed autologous CAR-T product, in Phase II trials across multiple autoimmune indications including multiple sclerosis, myasthenia gravis, and systemic sclerosis. Cabaletta Bio is running Phase I/II RESET trials with CABA-201 in inflammatory myositis and lupus. Neither program is specifically focused on autoimmune cytopenias, and the current report from Erlangen represents one of the few published accounts of antiphospholipid syndrome CAR-T treatment alongside AIHA and ITP in a single patient. Prof. Dr. Fabian Müller of University Hospital Erlangen served as corresponding author. The work was funded by the Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, the Bundesministerium für Bildung und Forschung, the Bayerisches Zentrum für Krebsforschung, the Interdisciplinary Center for Clinical Research Erlangen, and the Staedtler Foundation. Miltenyi Biotechnology provided the manufacturing platform and research support to authors at the institution. Meta description: Erlangen researchers report CD19 CAR-T remission in refractory autoimmune hemolytic anemia with concurrent ITP and antiphospholipid syndrome. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website