Evobrutinib

一、公司概况 （一）主营业务概况 公司是以自主研发能力为核心驱动力的创新生物医药企业，产品布局聚焦于血液瘤、自身免疫性疾病和实体瘤等领域覆盖小分子药物、单克隆抗体及双特异性抗体，注重构建具有协同效应的创新疗法，在全球开发具有突破性潜力的同类最佳或同类首创药物。 公司于2015年由拥有丰富新药研发及企业管理经验的崔霁松博士和世界著名结构生物学家施一公院士联合创立，经A/B1/C/D轮融资，公司分别于2020年、2022年在港交所、上交所科创板上市，为第五家A+H上市的生物医药公司。公司拥有2款商业化产品，自研核心产品奥布替尼（BTK抑制剂）于2020年获NMPA附条件批准用于r/r CLL/SLL和r/r MCL，引进产品坦昔妥单抗（CD19单抗）于2022年在中国香港获批用于r/r DLBCL。此外，公司13款产品处于临床阶段。 【1、r/r是复发或难治性的英文缩写，复发(Relapsed)：指患者在治疗后病情曾一度得到缓解（肿瘤缩小或消失），但一段时间后疾病再次出现或恶化。难治性 (Refractory)：指患者对治疗没有产生反应，或者在治疗结束后很短时间内（通常指6个月内）疾病就出现了进展。 CLL/SLL和MCL是两种不同类型的淋巴瘤，CLL/SLL指的是慢性淋巴细胞白血病/小淋巴细胞淋巴瘤： lCLL(慢性淋巴细胞白血病)：主要表现为外周血和骨髓中存在大量异常的淋巴细胞。 lSLL(小淋巴细胞淋巴瘤)：主要表现为淋巴结、脾脏等组织的肿大，但外周血中的异常淋巴细胞数量较少。 2、MCL指的是套细胞淋巴瘤。这是一种相对少见但通常更具侵袭性的B细胞非霍奇金淋巴瘤。它的特点是肿瘤细胞会广泛扩散，除了淋巴结肿大外，还常常累及骨髓、脾脏和胃肠道等部位。 3、DLBCL：指弥漫性大B细胞淋巴瘤。】 血液瘤领域以奥布替尼为核心疗法，并逐步叠加血液瘤领域丰富的在研药物，包括ICP-248（BCL-2抑制剂）、ICP-490（E3 Ligase）、ICP-B02（CD*CD20双抗）、坦昔妥单抗（CD19单抗），通过单药或联合疗法覆盖NHL、MM及白血病全领域。 【NHL是非霍奇金淋巴瘤(Non-Hodgkin Lymphoma)的英文缩写，它是一大类起源于淋巴结或淋巴组织的恶性肿瘤的总称，是淋巴瘤中最常见的类型，约占所有淋巴瘤的90%。NHL包含多种亚型，它们在细胞来源（主要是B细胞或T细胞）、生长速度（惰性或侵袭性）、临床表现和预后上都有很大差异。 MM是多发性骨髓瘤(Multiple Myeloma)的英文缩写，它是一种起源于骨髓中浆细胞的恶性肿瘤。浆细胞是负责产生抗体的免疫细胞，当它们发生癌变后会异常增殖。异常的浆细胞（骨髓瘤细胞）在骨髓中大量聚集，会抑制正常造血功能，并可能分泌异常的蛋白质（M蛋白），从而损害骨骼和肾脏等器官。其典型症状常被概括为“CRAB”：Calcium elevation (高钙血症)、Renal impairment (肾功能损害)、Anemia (贫血)、Bone disease (骨病，如骨痛、骨质疏松、病理性骨折)】 自免管线以奥布替尼和2款TYK2抑制剂为核心，针对B细胞信号通路异常引起的自身免疫性疾病，奥布替尼的在研适应症包括ITP（原发性血小板减少症）、SLE（系统性红斑狼疮）以及NMOSD（视神经脊髓炎谱系疾病）。其中ITP进入临床3期，SLE进入2期临床。针对T细胞信号通路异常引起的自免疾病，公司正在开发两款TYK2抑制剂ICP-332及ICP-488，根据两款化合物选择性不同，差异化布局AD（特异性皮炎）、银屑病等适应症。 实体瘤管线以小分子靶向抑制剂为主。两款潜在同类最佳分子（泛NTRK抑制剂ICP-723、FGFR抑制剂ICP-192）是公司进展最快2款实体瘤管线。公司通过肿瘤免疫/联合用药，逐步扩张实体瘤管线，ICP-189（SHP2抑制剂）、ICP-B05（CCR8单抗）等管线已进入临床阶段。 （二）团队情况 公司联合创始人、董事长兼首席执行官崔霁松博士具有逾20年医药行业研发和公司管理经验，曾任保诺科技的首席执行官兼首席科学官、默沙东美国心血管疾病早期开发团队负责人。 二、公司业务发展情况 （一）奥布替尼国内商业化潜力持续兑现 1、在NHL领域国内的市占率已达30%，且仍在持续增长 据弗若斯特沙利文的数据，2020年中国NHL患病总人数约为51万人，中国每年新发NHL患者人数约为7万人。当前中美共有6款BTK抑制剂获批上市，其中美国有4款，中国有5款。目前BTK抑制剂在B细胞淋巴瘤的细分适应症主要包括MCL（套细胞淋巴瘤）、CLL/SLL（慢性淋巴细胞白血病/小淋巴细胞淋巴瘤）、MZL（边缘区淋巴瘤）、WM（华氏巨球蛋白血症）以及FL（滤泡型淋巴瘤）。 据公司公告，奥布替尼在国内已获批r/r MCL、r/r CLL/SLL以及r/r MZL两三个适应症，其中r/r MZL为国内独家获批。1-3Q24奥布替尼实现收入6.亿人民币，同比增长45%，其中3Q单季度同比增速达75.5%，主要得益于独家适应症r/r MZL纳入医保后快速放量；我们预计奥布替尼2024年全年销售额有望达到10亿元，同比增长40%以上。根据各公司财报和PDB数据，按照销售额计算，奥布替尼在国内的市占率已达30%，仅次于泽布替尼，我们预计其未来仍有提升空间。 在国内市场，奥布替尼的主要竞争对手是百济神州的泽布替尼。两者都是国产第二代BTK抑制剂，上市时间相近，竞争激烈。虽然奥布替尼在MZL领域独占鳌头，但在更广阔的慢性淋巴细胞白血病（CLL）等适应症上，仍需与泽布替尼等产品正面竞争。 2、奥布替尼重启多发性硬化症开发 BTK抑制剂有望成为多发性硬化症领域一类高度有效的小分子口服药物。 多发性硬化症大类上可以分为复发性MS（RMS）和进行性MS（PMS）。根据美国多发性硬化症协会的数据，每年大约有85%的患者初诊为RRMS（复发-缓解型），随着疾病进展大约有80%的RRMS患者均将最终进展为SPMS（继发进展型）。此外还有大约10%的MS患者从发病开始就经历进展，为原发进行性MS（PPMS，原发进展型）患者，另有5%的患者初诊被诊断为进展复发型（PRMS，原发进展型）多发性硬化症。 根据Fortune Business Insights调研显示，2023全球MS药物的市场规模达213亿美元，其预计2032年将达到389.4亿美元，2024-2032年复合CAGR为7.9%。多发性硬化症用药市场高度分散，CD20单抗销售额迅速放量，尚缺安全性和疗效兼具的口服药。当前有多款BTK抑制剂正在布局多发性硬化症领域。其中赛诺菲、罗氏、默克的BTK抑制剂均已开展III期临床。 【中枢神经系统慢性炎性脱髓鞘性疾病，简单来说，就是身体的免疫系统“敌我不分”，错误地攻击了大脑、脊髓和视神经等部位的神经保护层，导致神经信号传递受阻或中断。这一疾病在医学分类上属于自身免疫性疾病，也是神经内科常见的罕见病之一。  RRMS、SPMS、PPMS、PRMS代表了多发性硬化症（MS）在病程发展上的四种不同阶段或类型，区分的核心在于判断病情是“发作后能好转”（复发-缓解），还是“一直在变差”（进展），或者是两者的混合。  多发性硬化症（MS）在全球和中国都属于“小病种”，全球存量患者约为280万，而中国目前的患者存量估计在3万至5.4万之间。】 BTK抑制剂折戟在RMS适应症，但在SPMS和PPMS仍有成药潜力。2024年9月，赛诺菲公布Tolebrutinib治疗MS的3项III期临床，治疗RMS的两项临床GEMINI1、GEMNIN2主要终点ARR分别达到0.12 vs 0.13(HR=1.06)、0.11 vs 0.11 (HR=1.00)，未取得统计学显著；但治疗nrSPMS的HERCULES达到主要终点，6个月确认的残疾进展（CDP）风险降低31%，成为首个也是唯一一个能延缓nrSPMS患者残疾累积的药物。 2022年12月，FDA对奥布替尼用于治疗多发性硬化症的II期临床实现部分临床搁置，停止患者招募，主要基于在使用奥布替尼的进行中的多发性硬化症II期研究及其他非多发性硬化症自身免疫性疾病的研究中，观察到有限数目的药物导致肝损伤的病例。2024年9月，FDA允许公司启动奥布替尼治疗原发进展型多发性硬化症（PPMS）的III期临床，并建议公司启动针对继发进展型多发性硬化症（SPMS）的III期临床。 BTK抑制剂折戟在RMS适应症，但在SPMS和PPMS仍有成药潜力。2024年9月，赛诺菲公布Tolebrutinib治疗MS的3项III期临床，治疗RMS的两项临床GEMINI1、GEMNIN2主要终点ARR分别达到0.12 vs 0.13 (HR=1.06)、0.11 vs 0.11(HR=1.00)，未取得统计学显著；但治疗nrSPMS的HERCULES达到主要终点，6个月确认的残疾进展（CDP）风险降低31%，成为首个也是唯一一个能延缓nrSPMS患者残疾累积的药物。 3、奥布替尼有望突围系统性红斑狼疮 狼疮是一类反复发作、难以治愈的自身免疫性疾病，传统激素和免疫抑制剂药物疗效不佳且副作用较大，仍存在未被满足的治疗需求。根据美国狼疮基金会和弗若斯特沙利文分析，2023年全球有超过500万狼疮患者，其中美国约150万，中国约100万。目前国内外医学指南推荐SLE的一线用药均为氯喹、激素及免疫抑制剂，生物制剂仅作为中重度复发患者与传统疗法联用的后线治疗。现在全球只有三款生物制剂获批治疗SLE，分别是贝利尤单抗、泰它西普和阿尼鲁单抗。但值得注意的是，贝利尤单抗和阿尼鲁单抗的临床数据对SLE疾病完全缓解效果有限，泰它西普虽然疗效可能较有优势，但没有头对头的三期临床数据去对比临床获益，且商业化和适应症仍在拓展中。因此我们认为SLE药物市场仍处于早期爬升阶段，临床在研的新机制药物有望成为市场成长的主力。 BTK抑制剂成为自身免疫性疾病研发的热门靶点，且具有口服制剂的患者依从性优势。与抗肿瘤药物需要对B细胞强杀伤能力不同，针对狼疮适应症的BTK抑制剂对安全性和选择性要求更高，临床设计的剂量通常比肿瘤适应症较低。但海外已有多个BTK抑制剂已停止SLE适应症的临床推进，包括但不限于Branebrutinib（BMS）、Elsubrutinib（艾伯维）、Fenebrutinib（Genentech）、Evobrutinib（Merck）等，主因疗效不足。目前奥布替尼在国内狼疮BTK抑制剂药进展领先，建议关注公司后续结果读出。 奥布替尼是全球首款在SLE中证实确有治疗效果的口服小分子BTK抑制剂，有望在国内市场率先获批。奥布替尼国内进度领先，于2022年3月公布12周SRI临床数据，数据呈现良好剂量依赖性。此外，公司还计划使用BTK抑制剂与TKY2抑制剂或者其他内部生物分子联合开发狼疮肾炎或神经精神性系统性红斑狼疮的临床计划。SLE IIb期临床试验预计2024年完成患者入组，建议关注后续中期分析节点。 4、奥布替尼切入免疫性血小板减少症 免疫性血小板减少症是一种获得性自发免疫性出血性疾病，以无明确诱因的孤立性外周血血小板减少为主要特点。目前国内尚无基于人口的ITP流行病学数据，国外报道的成人ITP年发病率为（2-10）/10万，60岁以上老年人是高发群体。根据和黄医药公告，2024年中国有25万人接受该疾病的治疗，市场规模预计在5-7亿美元。福他替尼是目前首个且唯一获批的口服Syk抑制剂，2018年获FDA批准，具备BIC潜力，但其有高血压(28%)、腹泻(31%)和恶心(19%)的不良反应。 BTK在B细胞和先天性免疫细胞中都有表达，是治疗免疫介导疾病的一个很有前景的靶点。阻断BTK信号分子对BCR和Fc受体通路的激活，可通过减少自身抗体产生和血小板吞噬作用来提高血小板数量。奥布替尼治疗ITP的II期临床数据显示，共有36%的患者达到了主要终点，30%患者达到持续应答；在既往有激素或IVIG应答史的22例患者中，50mg组的主要终点应答率为75%，持续应答率为50%；安全性表现良好，所有TRAE均为1-2级。 （二）CD19单抗Tafasitimab差异化切入r/r DLBCL市场 DLBCL二线治疗存在较高未被满足需求。根据《弥漫性大B细胞淋巴瘤诊疗指南》（卫健委，2022），接受R-CHOP治疗的1L DLBCL患者中有30%-40%的患者会在一线治疗后无效或在初始反应后复发，还有约10%-15%的患者属于原发性难治患者。因此共有约50%的r/r DLBCL患者不符合标准二线治疗、强化挽救治疗和自体干细胞移植的资格，DLBCL后线治疗存在较大的临床未满足需求。 Tafasitamab联合来那度胺最早于2020年7月获FDA批准上市，用于治疗2L以上不符合移植条件的DLBCL的药物。2021年8月17日，诺诚健华宣布就Tafasitamab与Incyte达成1.175亿美元和未来潜在销售分成的合作。2023年，Tafasitamab全球销售额达9200万美元。目前坦昔妥单抗正处于国内上市申报阶段，我们预计其有望2025年获批上市。 （三）TYK2是治疗特应性皮炎和银屑病的潜力口服药物 公司布局了两款差异化TYK2小分子口服药，分别是ICP-332和ICP-488。 1、ICP-332治疗特应性皮炎 特应性皮炎是一类Th2相关炎症性疾病，以往对中重度特应性皮炎的治疗手段相对有限，存在较大临床未满足需求。根据弗若斯特沙利文统计，2021年全球约有6.69亿特应性皮炎患者，中重度患者约占25%-30%；2021年中国特应性皮炎患者为6,900万人，其中中重度患者为1,900万人。近些年以度普利尤单抗（商品名：达必妥）为代表的靶向药物展现出优秀的临床效果，上市后迅速成为该领域的重磅产品。在全球市场，2023年达必妥销售额达107亿欧元，同比增长34%，再生元/赛诺菲预计2024年有望达到130亿欧元；在中国市场，2023年实现了30亿元销售额，同比增长100%，我们预计2024年可达40亿元。度普利尤单抗多项临床研究显示，患者使用该药物16周后皮肤皮损消失或几乎消失的患者比例约50%，此类患者则对JAK抑制剂或者TYK2等新型靶点药物有较大需求。 ICP-332展示了初步的安全性和有效性数据。ICP-332是公司自研的高选择性的TYK2抑制剂，主要通过抑制JAK1和TYK2来抑制II型炎症通路。II期数据显示，患者用药四周后，80mg和120mg两组的EASI-75应答率均为64%，明显高于对照组的8%；止痒效果明显，第2天开始出现响应并具有统计学意义；安全性表现良好，不良反应和耐受性与安慰剂相似。目前公司已启动ICP-332治疗特应性皮炎的III期临床，并提交了治疗的白癜风II/III期临床IND申请。此外，公司也在同步开展美国临床。 2、ICP-488治疗斑块状银屑病 银屑病是一种广泛发生的慢性炎症性多发系统疾病，国内市场处于快速起步阶段。银屑病影响全球数千万人，中重度患者占比可达20-30%，其可在中青年发病且无法根治，持续影响生活质量。银屑病生物制剂经历了由TNF-α抗体到IL-23/12抗体再到IL-17A/IL-23特异性抗体的迭代，IL-23与IL-17抗体能在较长给药间隔的同时，实现快速且持续的响应。上市较早的IL-12/23抗体乌司奴单抗2023年销售额达109亿美元，后续上市的IL-17A抗体响应快速，代表品种司库奇尤单抗、依奇珠单抗2023年销售额达77亿美元，IL-23 p19抗体长期疗效较好，代表品种古塞奇尤单抗及瑞莎珠单抗等2023年合计销售额达109亿美元。 虽然生物制剂在银屑病治疗的疗效方面取得了较好的成果，但大分子药物注射给药的方式和相对高昂的价格仍对患者的长期用药依从性存在影响，因此可开发为外用或口服剂型的小分子药物仍然是银屑病新药开发的重要方向。PDE4抑制剂有局部外用与口服药物两种剂型，可用于轻中重度银屑病的治疗；JAK抑制剂存在心血管相关风险等黑框警告，目前主要用于银屑病性关节炎，但其中选择性TYK2抑制剂在安全性改善的同时，临床中展现出优于已有PDE4抑制剂的治疗效果，是银屑病小分子药物的重要开发方向之一，Deucravacitinib（BMS）在2022年9月获得FDA批准，成为首个上市的TYK2抑制剂。 ICP-488是公司自研的高选择性的TYK2抑制剂，主要通过抑制子IL-12和IL-23的受体以及I型干扰素受体来抑制Th17和Tc17通路。II期数据显示，患者用药12周后，6mg和90mg两组的PASI-75应答率分别为77.3%和78.6%，明显高于对照组的11.6%；安全性表现良好，不良反应和耐受性与安慰剂相似。 三、盈利预测与业绩跟踪情况 （一）盈利预测 考虑到公司2024年奥布替尼MZL适应症纳入医保后开始快速放量，我们预计2024年开始公司收入将逐步加快，我们预计诺诚健华2024-2026年收入分别为10.08/13.42 /18.30亿元，分别对应同比增长36.5%/33.2% /36.3%，我们预计公司2024-2026年净亏损分别4.81 /4.36 /2.56亿元。 我们预计未来两年销售收入上涨主要来自于奥布替尼和Tafasitamab销售贡献，远期收入上涨主要来自于奥布替尼自免适应症和ICP-332/ICP-488销售贡献。考虑到公司已进入销售稳定放量期，我们预计24年及未来毛利率维持在86-88%。 （二）业绩跟踪情况 1、中金公司2025年1月的研究报告 公司BTK抑制剂奥布替尼自2024年初MZL（边缘区淋巴瘤）适应症纳入医保后快速放量，1-3Q24贡献收入6.93亿元，公司3Q24公告预计该产品全年收入继续保持高增长。据我们测算，2024年国内BTK市场规模约30亿元，其中公司奥布替尼市占率已达30%，预计仍有上升空间。 此外公司血液瘤管线持续扩充，引入的CD19单抗Tafasitamab治疗r/r DLBCL上市申请已获受理并纳入优先审评，有望继续提升公司在血液瘤的领先优势。 9M24 FDA同意启动奥布替尼治疗原发进展型多发性硬化（PPMS）的III期临床研究，并建议启动奥布替尼治疗继发进展型多发性硬化（SPMS）的III期临床研究。 奥布替尼也在探索红斑狼疮和免疫性血小板减少症两个适应症，均处于II期临床阶段。此外，公司两款差异性TYK2口服小分子ICP-332和ICP-488正在分别开发特应性皮炎和银屑病适应症，目前均已完成II期临床，国内进度领先。 2、中金公司2026年4月的研究报告 2025年奥布替尼实现销售收入14.10亿元，同比增长40.99%，我们预计其主要受益于独家适应症MZL持续放量；奥布替尼新增1L CLL/SLL适应症，并顺利纳入医保，价格稳定。 坦昔妥单抗tafasitamab于5M25获CDE批准上市用于治疗DLBCL，这是中国首个获批治疗R/R DLBCL的CD19单抗。2025年确认BD收入9.04亿元，其中1H25与Prolium达成合作确认收入877万美元，2H25与Zenas达成合作确认3,715万美元付款以及500万股Zenas普通股。 奥布替尼用于PPMS的III期临床已于3Q25启动，用于naSPMS的III期临床计划1Q26启动；ITP适应症III期临床已完成，公司预计1H26递交NDA；SLE的IIb期临床达到主要终点，公司预计1H26启动III期。 ICP-332（TYK-2/JAK1）的特应性皮炎III期临床将于26年年中读出数据，以及ICP-488（TYK-2, allosteric）的银屑病III期临床均已完成患者入组。 ICP-248（BCL2）联合奥布替尼用于治疗1L CLL/SLL的中国III期临床已完成患者入组。除此之外，ICP-723（泛TRK抑制剂zurletrectinib）已于2025年获批上市。另外，公司自主研发的ICP-B794（B7H3 ADC）正推进临床I期剂量递增临床；ICP-B208（CDH17 ADC）已递交IND申请。 目前来看，公司的业务发展基本符合券商的预期，前景可以期待。

1、研究机构：赛诺菲制药、健赞生物制药、Principia Biopharma 2、别名：PRN-2246、SAR-442168、Cenrifki、托莱布替尼 3、靶点：BTK 4、剂型及给药途径：普通片剂; 口服给药 5、结构式 6、适应症及进展 适应症 进展 最新进展日期 多发性硬化 申请上市 2026-03-07 2026-03-07 I期 2025-02-07 7、发表论文 标题 内容类型 适应症 企业 技术平台 来源 发表日期 BTK regulates microglial function and neuroinflammation in human stem cell models and mouse models of multiple sclerosis 药理研究 多发性硬化 赛诺菲制药 武田药品工业株式会社 Voyager Therapeutics Nat Commun IF=15.7 2024-11-22 8、交易 交易名称 交易类型 转让方 受让方 交易时研发状态 权益类型 权益地区 权益适应症 交易金额 交易时间 Sanofi completes Principia Biopharma Inc. acquisition收购完成 转让/收购 Principia Biopharma 赛诺菲制药 临床III期 开发/商业化权 交易总额：3680百万美元  2020-09-28 Sanofi to acquire Principia Biopharma 转让/收购 Principia Biopharma 赛诺菲制药 临床III期 开发/商业化权 交易总额：3680百万美元  2020-08-17 Bay Area's Principia Biopharma Scores $765M MS Licensing Deal With Drug Giant Sanofi 授权/许可 Principia Biopharma 赛诺菲制药 临床II期 开发/商业化权 交易总额：765百万美元首付款：40百万美元 2017-11-09 9、专利布局 公开（公告）号 专利主题 发明名称 申请日 法律状态 CN106459049B 化合物 酪氨酸激酶抑制剂 2016-06-02 CN118434732A 晶型 Tolebrutinib的晶型及其制备方法和用途 2021-11-22 实质审查 CN117897381A 晶型 Tolebrutinib的晶型及其制备方法和用途 2022-06-02 实质审查 CN118434734A 晶型 (R)-1-(1-丙烯酰基哌啶-3-基)-4-氨基-3-(4-苯氧基苯基)-1H-咪唑并[4,5-C]吡啶-2(3H)-酮及其盐的晶型 2022-12-20 实质审查 CN119212708A 用途 用于髓鞘少突胶质细胞糖蛋白抗体疾病(MOGAD)的治疗性酪氨酸激酶抑制剂 2023-05-12 实质审查 CN119384411A 制备工艺 制备托勒替尼的方法 2023-06-13 实质审查 CN119343340A 制备工艺 制备修饰的BTK抑制剂的方法 2023-06-21 实质审查 CN119421712A 用途 用于多发性硬化和重症肌无力的治疗性酪氨酸激酶抑制剂 2023-06-29 实质审查 CN120435291A 用途 用于多发性硬化的治疗性酪氨酸激酶抑制剂 2023-10-06 实质审查 CN120379652A 制剂 (R)-1-(1-丙烯酰基哌啶-3-基)-4-氨基-3-(4-苯氧基苯基)-1H-咪唑并[4,5-c]吡啶-2(3H)-酮的药物制剂 2023-12-19 实质审查 CN121620370A 用途 通过检测脑脊液中的生物标志物诊断和治疗多发性硬化的方法 2024-01-31 实质审查 10、研究历程 2025年02月01日，由赛诺菲向美国食品药品管理局FDA提交上市申请，用于治疗慢性进行性多发性硬化。（https://www.sanofi.com/en/our-science/our-pipeline） 2024年05月20日，由Sanofi Winthrop Industrie SA在中国香港和中国大陆开展临床三期试验，用于治疗多发性硬化。（CTR20240417） 2024年04月16日，由赛诺菲（中国）投资有限公司、Sanofi Winthrop Industrie SA、Sanofi-Aventis Recherche & Developpement和赛诺菲在澳大利亚、加拿大和智利等国家和地区开展临床三期试验，用于治疗多发性硬化和慢性进行性多发性硬化。（CTR20240417; NCT06372145） 2023年03月10日，治疗重症肌无力的研究终止。（NCT05132569） 2022年12月14日，治疗重症肌无力的研究终止。（CTR20220329） 2022年06月22日，由赛诺菲（中国）投资有限公司、Sanofi Winthrop Industrie SA和Sanofi-Aventis Recherche & Developpement在中国大陆开展临床三期试验，用于治疗重症肌无力。（CTR20220329） 2022年03月10日，由赛诺菲在德国和美国开展临床一期试验，用于治疗肾功能不全。（NCT05282030） 2021年12月20日，由赛诺菲（中国）投资有限公司、Sanofi Winthrop Industrie SA和Sanofi-Aventis Recherche & Developpement在巴西、加拿大和德国等国家和地区开展临床三期试验，用于治疗重症肌无力。（CTR20220329） 2021年12月03日，由赛诺菲在加拿大、匈牙利和意大利等国家和地区开展临床三期试验，用于治疗重症肌无力。（NCT05132569） 2021年11月03日，由Koneksa Health Inc开展临床前研究试验。（https://www.prnewswire.com/news-releases/koneksa-broadens-multi-year-cns-research-collaboration-with-sanofi-301415238.html） 2021年04月15日，由National Institute Of Neurological Disorders And Stroke在美国开展临床二期试验，用于治疗多发性硬化。（NCT04742400） 2021年02月23日，由赛诺菲（中国）投资有限公司、Sanofi-Aventis Recherche & Developpement和美国健赞公司在中国香港、中国台湾和中国大陆等国家和地区开展临床三期试验，用于治疗多发性硬化。（CTR20240417; CTR20210060; CTR20202631; CTR20210121） 2020年10月23日，由赛诺菲（中国）投资有限公司、Sanofi-Aventis Recherche & Developpement和美国健赞公司在奥地利、白俄罗斯和保加利亚等国家和地区开展临床三期试验，用于治疗多发性硬化。（CTR20240417; CTR20210060） 2020年08月13日，由赛诺菲在阿根廷、澳大利亚和奥地利等国家和地区开展临床三期试验，用于治疗慢性进行性多发性硬化。（NCT04458051; NCT06372145） 2020年06月30日，由赛诺菲在奥地利、白俄罗斯和保加利亚等国家和地区开展临床三期试验，用于治疗多发性硬化。（NCT06372145; NCT04410978） 2020年06月11日，由赛诺菲在阿根廷、比利时和巴西等国家和地区开展临床三期试验，用于治疗多发性硬化。（NCT06372145; NCT04410978; NCT04410991） 2020年05月18日，由赛诺菲在美国开展临床一期试验，用于治疗多发性硬化。（NCT06106074; NCT06064539） 2019年11月13日，由赛诺菲在英国开展临床一期试验，用于治疗多发性硬化。（NCT04171310） 2019年03月29日，由赛诺菲在加拿大、爱沙尼亚和法国等国家和地区开展临床二期试验，用于治疗多发性硬化。（NCT03996291; NCT03889639） 11、临床试验 登记号 试验标题 试验药 适应症 原始适应症 申办/合作机构 试验状态 试验分期 开始日期 完成日期 国家/地区 NCT07526597 Study on Treatment Outcome Patterns for Patients With CLL After Discontinuation of BTK Inhibitors 托莱布替尼 慢性淋巴细胞白血病 | 小淋巴细胞淋巴瘤 Chronic Lymphocytic Leukemia | Small Lymphocytic Lymphoma Lineberger Comprehensive Cancer Center Not yet recruiting 临床2期 2026-05-01 2032-06-01 美国 NCT07120633 The Efficacy of AntiCD19 CAR-T Combined With BTKi in the Treatment of Newly Diagnosed High-risk CLL Patients, and to Explore Its Efficacy and Safety of Limited-term Treatment in These Patients Anti-CD19 CAR-T (The Affiliated Hospital of Xuzhou Medical University) | 托莱布替尼 慢性淋巴细胞白血病 | 小淋巴细胞淋巴瘤 CLL | CAR-T Cell Therapy | SLL 徐州医科大学附属医院 Recruiting N/A 2025-09-01 2028-09-01 中国 NCT06372145 An Interventional, Phase 3 Extension Study to Investigate Long-term Safety and Tolerability of Tolebrutinib in Participants With Relapsing Multiple Sclerosis, Primary Progressive Multiple Sclerosis, or Nonrelapsing Secondary Progressive Multiple Sclerosis 托莱布替尼 (片剂, 口服) 原发性进行性多发性硬化 | 继发进展型多发性硬化 | 复发性多发性硬化 Relapsing Multiple Sclerosis | Secondary Progressive Multiple Sclerosis | Progressive Relapsing Multiple Sclerosis Sanofi Active, not recruiting 临床3期 2024-04-16 2029-04-30 美国 | 中国香港 | 捷克 | 泰国 | 葡萄牙 | 希腊 | 瑞典 | 韩国 | 荷兰 | 拉脱维亚 | 奥地利 | 中国 | 土耳其 | 波兰 | 巴西 | 斯洛伐克 | 塞尔维亚共和国 | 立陶宛 | 法国 | 智利 | 保加利亚 | 克罗地亚 | 哥伦比亚 | 阿根廷 | 罗马尼亚 | 匈牙利 | 日本 | 乌克兰 | 英国 | 瑞士 | 西班牙 | 印度 | 加拿大 | 比利时 | 挪威 | 中国台湾 | 芬兰 | 丹麦 | 南非 | 墨西哥 | 意大利 | 以色列 | 澳大利亚 | 德国 | 爱沙尼亚 NCT06106074 A Randomized, Double-blind, Placebo-controlled Study of the Tolerability and Pharmacokinetics of Ascending Single and 14-day Repeated Oral Doses of SAR442168 With a Food Effect Investigation in Healthy Adult Participants 托莱布替尼 (片剂, 口服) 多发性硬化症 Multiple Sclerosis Sanofi Completed 临床1期 2020-08-10 2022-05-23 美国 NCT06064539 A Phase 1, Single-center, Open-label, Two-cohort, Two-period, One-sequence, Two Treatment, Drug-drug Interaction Study of the Effects of Gemfibrozil and Rifampicin on SAR442168 in Healthy Subjects 吉非罗齐 (片剂, 口服) | 利福平 (片剂, 口服) | 托莱布替尼 (片剂, 口服) 多发性硬化症 Multiple Sclerosis Sanofi Completed 临床1期 2020-05-18 2020-07-08 美国 NCT05283915 An Open-label Phase 1, Pharmacokinetic and Tolerability Study of Tolebrutinib Given as a Single Dose in Adult Participants With Mild Hepatic Impairment, and in Matched Participants With Normal Hepatic Function 托莱布替尼 (薄膜包衣片, 口服) 肝功能不全 Hepatic Function Abnormal Sanofi Completed 临床1期 2022-03-18 2022-05-24 美国 NCT05282030 An Open-label, Multi-center Phase 1 Pharmacokinetic and Tolerability Study of Tolebrutinib Given as a Single Oral Dose in Participants With Renal Impairment and in Matched Participants With Normal Renal Function. 托莱布替尼 (薄膜包衣片, 口服) 肾功能不全 Renal Impairment Sanofi Completed 临床1期 2022-03-10 2022-08-02 美国 | 德国 ChiCTR2200055554 An Open, Single-Center Clinical Observation Study to Assess the Efficacy and Safety of The Thiotepa for Primary Central Nervous System Lymphoma (PCNSL) Patients 卡莫司汀 | 托莱布替尼 | 甲氨蝶呤 | 利妥昔单抗 | 塞替派 原发性中枢神经系统淋巴瘤 Primary central nervous system lymphoma/Central?high?risk?of?diffuse?large?B-cell?lymphoma 兰州大学第二医院 Recruiting 临床2期 2022-04-01 2024-04-04 中国 NCT05132569 A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Tolebrutinib (SAR442168) in Adults With Generalized Myasthenia Gravis (MG) 托莱布替尼 (薄膜包衣片, 口服) 重症肌无力 Myasthenia Gravis Sanofi Terminated 临床3期 2021-12-03 2023-02-21 加拿大 | 匈牙利 | 美国 | 日本 | 中国 | 波兰 | 英国 | 意大利 | 西班牙 NCT04978779 An Open-label, Multicenter Phase 1/1b Study to Characterize Safety, Tolerability, Preliminary Antitumor Activity, Pharmacokinetics, and Pharmacodynamics of VIP152 Monotherapy or Combination Therapy in Subjects With High-risk Chronic Lymphocytic Leukemia or Richter Syndrome Enitociclib (静脉注射) | 托莱布替尼 染色体易位 | 复发性非霍奇金淋巴瘤 | 难治性慢性淋巴细胞白血病 | 里氏综合症 Relapsed Non Hodgkin Lymphoma | Chronic Lymphocytic Leukemia | Refractory Chronic Lymphocytic Leukemia | Richter Syndrome | MYC Amplification | MYC Overexpression | MYC Translocation Vincerx Pharma, Inc. Terminated 临床1期 2021-12-16 2023-05-26 美国 | 波兰 NCT04742400 A Phase 2 Clinical Trial of Tolebrutinib, a Brain-penetrant Bruton's Tyrosine Kinase Inhibitor, for the Modulation of Chronically Inflamed White Matter Lesions in Multiple Sclerosis 托莱布替尼 (口服) 多发性硬化症 Multiple Sclerosis National Institute of Neurological Disorders & Stroke Active, not recruiting 临床2期 2021-04-15 2025-12-31 美国 NCT04458051 A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Primary Progressive Multiple Sclerosis (PERSEUS) 托莱布替尼 (薄膜包衣片, 口服) 原发性进行性多发性硬化 Primary Progressive Multiple Sclerosis Sanofi Completed 临床3期 2020-08-13 2025-11-14 捷克 | 美国 | 泰国 | 葡萄牙 | 俄罗斯 | 希腊 | 瑞典 | 荷兰 | 拉脱维亚 | 奥地利 | 中国 | 土耳其 | 波兰 | 巴西 | 塞尔维亚共和国 | 法国 | 智利 | 保加利亚 | 克罗地亚 | 哥伦比亚 | 阿根廷 | 罗马尼亚 | 匈牙利 | 日本 | 乌克兰 | 英国 | 白俄罗斯 | 西班牙 | 印度 | 加拿大 | 比利时 | 挪威 | 丹麦 | 南非 | 墨西哥 | 意大利 | 以色列 | 澳大利亚 | 秘鲁 | 德国 | 爱沙尼亚 NCT04411641 A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis 托莱布替尼 (薄膜包衣片, 口服) 继发进展型多发性硬化 Non-relapsing Secondary Progressive Multiple Sclerosis Sanofi Completed 临床3期 2020-09-24 2024-08-29 俄罗斯 | 捷克 | 美国 | 葡萄牙 | 希腊 | 荷兰 | 奥地利 | 中国 | 波兰 | 立陶宛 | 法国 | 保加利亚 | 阿根廷 | 罗马尼亚 | 匈牙利 | 日本 | 乌克兰 | 英国 | 白俄罗斯 | 西班牙 | 印度 | 加拿大 | 土耳其 | 比利时 | 挪威 | 芬兰 | 丹麦 | 意大利 | 以色列 | 澳大利亚 | 德国 NCT04410978 A Phase 3, Randomized, Double-blind Efficacy and Safety Study Comparing SAR442168 to Teriflunomide (Aubagio®) in Participants With Relapsing Forms of Multiple Sclerosis 托莱布替尼 (片剂, 口服) 复发性多发性硬化 Relapsing Multiple Sclerosis Sanofi Completed 临床3期 2020-06-30 2024-07-15 俄罗斯 | 罗马尼亚 | 中国香港 | 捷克 | 美国 | 日本 | 乌克兰 | 白俄罗斯 | 西班牙 | 加拿大 | 瑞典 | 奥地利 | 土耳其 | 中国 | 中国台湾 | 芬兰 | 波兰 | 丹麦 | 墨西哥 | 意大利 | 立陶宛 | 保加利亚 | 德国 | 爱沙尼亚 NCT04171310 An Open-label Study of Excretion Balance and Pharmacokinetics Following a Single Oral Dose of [14C]-SAR442168 (Not More Than 3.7 MBq) in Healthy Male Subjects 托莱布替尼 多发性硬化症 Multiple Sclerosis Sanofi Completed 临床1期 2019-11-13 2019-12-30 英国 KCT0004309 A Phase 1, single-center, randomized, double-blind, placebo-controlled, incomplete block, 3-period crossover, single-dose escalation study to determine the safety, tolerability and pharmacokinetics of orally administered SAR442168 tablet in healthy East Asian (Japanese / Chinese / Korean) male subjects 托莱布替尼 神经系统疾病 Diseases of the nervous system Sanofi-Aventis Korea Co., Ltd. Completed 临床1期 2019-08-13 - 韩国 NCT03996291 Long-term Extension Safety and Efficacy Study of SAR442168 in Participants With Relapsing Multiple Sclerosis 托莱布替尼 复发性多发性硬化 Relapsing Multiple Sclerosis Sanofi Completed 临床2期 2019-09-23 2024-11-26 加拿大 | 荷兰 | 捷克 | 美国 | 乌克兰 | 法国 | 西班牙 | 俄罗斯 | 爱沙尼亚 NCT03889639 A Phase 2b Dose-finding Study for SAR442168, a Bruton's Tyrosine Kinase Inhibitor, in Participants With Relapsing Multiple Sclerosis 托莱布替尼 复发性多发性硬化 Relapsing Multiple Sclerosis Sanofi Completed 临床2期 2019-03-29 2020-01-02 加拿大 | 荷兰 | 捷克 | 美国 | 乌克兰 | 斯洛伐克 | 法国 | 西班牙 | 俄罗斯 | 爱沙尼亚 ACTRN12618001523291 A Phase 1, Randomized, Open-Label Study of the Relative Bioavailability and Effect of Food on the Pharmacokinetics of a Novel Formulation of PRN2246 Compared to a Reference Formulation in Healthy Adult Participants 托莱布替尼 多发性硬化症 | 神经系统疾病 Immune-mediated neurologic disorders | Immune-mediated neurologic disorders | Neurological - Multiple sclerosis Clinical Network Services Pty Ltd. Completed 临床1期 2018-10-14 2018-11-09 澳大利亚 ACTRN12617001457336 A Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered PRN2246 in Healthy Volunteers 托莱布替尼 神经系统疾病 Immune-mediated neurologic disorders Clinical Network Services Pty Ltd. Recruiting 临床1期 2017-10-17 - - 12、临床结果 标题 登记号 来源 分期 适应症 评价人数 用药方案 结果 评价 发布日期 申办/合作机构 主要研究药物 来源链接 Synapse链接 TP53 aberrant Mantle Cell Lymphoma treated with first-line systemic therapy: A real-world analysis of outcomes in 120 patients treated in the United Kingdom - ASH N/A 套细胞淋巴瘤 120 High intensity ICT (rituximab + high dose cytarabine based) CR = 45.0 %  不佳 2025-12-06 University Hospital Southampton NHS Foundation Trust | Barts Health NHS Trust | Blackpool Teaching Hospitals NHS Foundation Trust | South Tees Hospitals NHS Foundation Trust | Nottingham University Hospitals Nhs Trust | University College London Hospitals NHS Foundation Trust - https://meetings-api.hematology.org/api/abstract/vmpreview/300472 https://synapse.zhihuiya.com/clinical-result-detail/82ed9a2825328852205ea4ee592a5358 TP53 aberrant Mantle Cell Lymphoma treated with first-line systemic therapy: A real-world analysis of outcomes in 120 patients treated in the United Kingdom - ASH N/A 套细胞淋巴瘤 120 Intermediate intensity ICT (R-CHOP/R- Bendamustine/R-BAC/VR-CAP) FFS(1st line) = 8.9 Month ( 3.8 ~ 14.0) 不佳 2025-12-06 University Hospital Southampton NHS Foundation Trust | Barts Health NHS Trust | Blackpool Teaching Hospitals NHS Foundation Trust | South Tees Hospitals NHS Foundation Trust | Nottingham University Hospitals Nhs Trust | University College London Hospitals NHS Foundation Trust - https://meetings-api.hematology.org/api/abstract/vmpreview/300472 https://synapse.zhihuiya.com/clinical-result-detail/82ed9a2825328852205ea4ee592a5358 Real-world outcomes of younger patients with chronic lymphocytic leukemia treated with first-line BTK inhibitor or BCL2 inhibitor therapy - ASH N/A 慢性淋巴细胞白血病 426 BTKi (ibrutinib, acalabrutinib, or zanubrutinib) mDoT = 20.7 Month  积极 2025-12-06 University of Utah Spencer Fox Eccles School of Medicine - https://meetings-api.hematology.org/api/abstract/vmpreview/300991 https://synapse.zhihuiya.com/clinical-result-detail/a335842a820a8a504d2a223a038ea2e2 Real-world outcomes of younger patients with chronic lymphocytic leukemia treated with first-line BTK inhibitor or BCL2 inhibitor therapy - ASH N/A 慢性淋巴细胞白血病 426 BCL2i (venetoclax ± rituximab or obinutuzumab) mDoT = 11.9 Month  积极 2025-12-06 University of Utah Spencer Fox Eccles School of Medicine - https://meetings-api.hematology.org/api/abstract/vmpreview/300991 https://synapse.zhihuiya.com/clinical-result-detail/a335842a820a8a504d2a223a038ea2e2 Outcomes of patients with Richter transformation (RT) treated with frontline chemoimmunotherapy (CIT) and BTK inhibitor (BTKi) - ASH N/A 里氏综合症 56 CIT+BTKi ORR = 62.5 %  积极 2025-12-06 University of California - https://meetings-api.hematology.org/api/abstract/vmpreview/291372 https://synapse.zhihuiya.com/clinical-result-detail/a25243a9e42aee422543ad5522aa24d3 Outcomes of patients with Richter transformation (RT) treated with frontline chemoimmunotherapy (CIT) and BTK inhibitor (BTKi) - ASH N/A 里氏综合症 56 CIT-only CR = 58.3 %  积极 2025-12-06 University of California - https://meetings-api.hematology.org/api/abstract/vmpreview/291372 https://synapse.zhihuiya.com/clinical-result-detail/a25243a9e42aee422543ad5522aa24d3 Upfront continuous BTK inhibitor (BTKi) versus time-limited venetoclax-BTKi combinations in CLL across IGHV subgroups: Results of an indirect analysis - ASH N/A 慢性淋巴细胞白血病 2037 continuous BTKi therapy PFS(four-year): Δ = 0.5(95.0% CI, -4.8 ~ 5.8), P-Value = 0.85 积极 2025-12-06 - 托莱布替尼 https://meetings-api.hematology.org/api/abstract/vmpreview/291473 https://synapse.zhihuiya.com/clinical-result-detail/00482ea9a5ae42545259ea22de2249e5 Upfront continuous BTK inhibitor (BTKi) versus time-limited venetoclax-BTKi combinations in CLL across IGHV subgroups: Results of an indirect analysis - ASH N/A 慢性淋巴细胞白血病 2037 TL venetoclax-BTKi regimens PFS(four-year): Δ = 0.5(95.0% CI, -4.8 ~ 5.8), P-Value = 0.85 积极 2025-12-06 - 托莱布替尼 https://meetings-api.hematology.org/api/abstract/vmpreview/291473 https://synapse.zhihuiya.com/clinical-result-detail/00482ea9a5ae42545259ea22de2249e5 Comparison of infections in patients with chronic lymphocytic leukemia (CLL) treated with BTKi versus venetoclax obinutuzumab in first line therapy - ASH N/A 慢性淋巴细胞白血病 3178 BTKi (ibrutinib, zanubrutinib, or acalabrutinib) 菌血症 = 8.1 %  不佳 2025-12-06 Roswell Park Comprehensive Cancer Center 托莱布替尼 https://meetings-api.hematology.org/api/abstract/vmpreview/290555 https://synapse.zhihuiya.com/clinical-result-detail/59525e99a0325ad52ad42ed5382a22aa Comparison of infections in patients with chronic lymphocytic leukemia (CLL) treated with BTKi versus venetoclax obinutuzumab in first line therapy - ASH N/A 慢性淋巴细胞白血病 3178 VenObin (venetoclax & obinutuzumab) 菌血症 = 4.8 %  不佳 2025-12-06 Roswell Park Comprehensive Cancer Center 托莱布替尼 https://meetings-api.hematology.org/api/abstract/vmpreview/290555 https://synapse.zhihuiya.com/clinical-result-detail/59525e99a0325ad52ad42ed5382a22aa Characteristics, treatment outcomes, and prognostic analysis of 118 cases of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia - ASH N/A 淋巴浆细胞性淋巴瘤 | 巨球蛋白血症 101 BTKi (Bruton Tyrosine kinase inhibitor, Ibrutinib 140mg QD, or Zanubrutinib 160mg BID) CRR = 100.0 %  积极 2025-12-06 - 托莱布替尼 https://meetings-api.hematology.org/api/abstract/vmpreview/302249 https://synapse.zhihuiya.com/clinical-result-detail/e82a5e2894a082a8408a8e89ade32804 Characteristics, treatment outcomes, and prognostic analysis of 118 cases of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia - ASH N/A 淋巴浆细胞性淋巴瘤 | 巨球蛋白血症 101 VD (Bortezomib 1.3mg/m2,d1,8,15, Dexamethasone, 20mg, d1,2,8,9,15,16,22,23) mOS = NR   积极 2025-12-06 - 托莱布替尼 https://meetings-api.hematology.org/api/abstract/vmpreview/302249 https://synapse.zhihuiya.com/clinical-result-detail/e82a5e2894a082a8408a8e89ade32804 Progression of disease within 36 months (POD36) of starting first-line targeted therapy independently predicts poor overall survival in patients with chronic lymphocytic leukemia (CLL) - ASH N/A 慢性淋巴细胞白血病 787 BTKi +/- CD20mAb mOS = not reached   积极 2025-12-06 Mayo Clinic 托莱布替尼 https://meetings-api.hematology.org/api/abstract/vmpreview/292616 https://synapse.zhihuiya.com/clinical-result-detail/0a582a8e8e4e82d002a88403ea958e22 Progression of disease within 36 months (POD36) of starting first-line targeted therapy independently predicts poor overall survival in patients with chronic lymphocytic leukemia (CLL) - ASH N/A 慢性淋巴细胞白血病 787 BCL2i + CD20mAb mOS = not reached   积极 2025-12-06 Mayo Clinic 托莱布替尼 https://meetings-api.hematology.org/api/abstract/vmpreview/292616 https://synapse.zhihuiya.com/clinical-result-detail/0a582a8e8e4e82d002a88403ea958e22 Real-world comparison of treatment outcomes between BCL2i and 2nd generation BTKi therapy in first-line CLL patients - ASH N/A 慢性淋巴细胞白血病 3844 Second-generation BTKi Event-free probability(30-month) = 70.0 %  积极 2025-12-06 - 维奈克拉 | 奥妥珠单抗 https://meetings-api.hematology.org/api/abstract/vmpreview/297011 https://synapse.zhihuiya.com/clinical-result-detail/02e232eea4d0a32325242482e5588a3e Real-world comparison of treatment outcomes between BCL2i and 2nd generation BTKi therapy in first-line CLL patients - ASH N/A 慢性淋巴细胞白血病 3844 V+O Event-free probability(30-month) = 83.0 %  积极 2025-12-06 - 维奈克拉 | 奥妥珠单抗 https://meetings-api.hematology.org/api/abstract/vmpreview/297011 https://synapse.zhihuiya.com/clinical-result-detail/02e232eea4d0a32325242482e5588a3e A Phase 3, Randomized, Double-blind Efficacy and Safety Study Comparing SAR442168 to Teriflunomide (Aubagio®) in Participants With Relapsing Forms of Multiple Sclerosis NCT04410978 CTgov 临床3期 复发性多发性硬化 974 Teriflunomide(Teriflunomide 14 mg) Annualized Relapse Rate (ARR) as Assessed by Confirmed Protocol-defined Adjudicated Relapses = 0.122 relapses per participant year (95%CI, 0.100 ~ 0.150) - 2025-06-18 Sanofi 托莱布替尼 https://clinicaltrials.gov/ct2/show/results/NCT04410978 https://synapse.zhihuiya.com/clinical-result-detail/aa855a8320d22a542424eaa85889e239 A Phase 3, Randomized, Double-blind Efficacy and Safety Study Comparing SAR442168 to Teriflunomide (Aubagio®) in Participants With Relapsing Forms of Multiple Sclerosis NCT04410978 CTgov 临床3期 复发性多发性硬化 974 Tolebrutinib(Tolebrutinib 60 mg) Annualized Relapse Rate (ARR) as Assessed by Confirmed Protocol-defined Adjudicated Relapses = 0.130 relapses per participant year (95%CI, 0.108 ~ 0.156) - 2025-06-18 Sanofi 托莱布替尼 https://clinicaltrials.gov/ct2/show/results/NCT04410978 https://synapse.zhihuiya.com/clinical-result-detail/aa855a8320d22a542424eaa85889e239 A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis NCT04411641 CTgov 临床3期 继发进展型多发性硬化 1131 placebo+tolebrutinib(DB: Placebo) Time to Onset of 6-Month Confirmed Disability Progression (CDP) as Assessed by Expanded Disability Status Scale (EDSS)(Median) = 11.97 Month (Full Range, 0.5 ~ 39.1) - 2025-06-18 Sanofi 托莱布替尼 https://clinicaltrials.gov/ct2/show/results/NCT04411641 https://synapse.zhihuiya.com/clinical-result-detail/888e2aed428e888334e855ae28d4894e A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis NCT04411641 CTgov 临床3期 继发进展型多发性硬化 1131 Tolebrutinib(DB: Tolebrutinib 60 mg) Time to Onset of 6-Month Confirmed Disability Progression (CDP) as Assessed by Expanded Disability Status Scale (EDSS)(Median) = 12.04 Month (Full Range, 2.8 ~ 37.4) - 2025-06-18 Sanofi 托莱布替尼 https://clinicaltrials.gov/ct2/show/results/NCT04411641 https://synapse.zhihuiya.com/clinical-result-detail/888e2aed428e888334e855ae28d4894e A Phase 3, Randomized, Double-blind Efficacy and Safety Study Comparing SAR442168 to Teriflunomide (Aubagio®) in Participants With Relapsing Forms of Multiple Sclerosis NCT04410991 CTgov 临床3期 复发性多发性硬化 899 Teriflunomide(Teriflunomide 14 mg) Annualized Relapse Rate (ARR) as Assessed by Confirmed Protocol-defined Adjudicated Relapses = 0.109 relapses per participant year (95%CI, 0.088 ~ 0.134) - 2025-06-18 Sanofi 托莱布替尼 https://clinicaltrials.gov/ct2/show/results/NCT04410991 https://synapse.zhihuiya.com/clinical-result-detail/e23e3a42323d22a53223aa0422482855 A Phase 3, Randomized, Double-blind Efficacy and Safety Study Comparing SAR442168 to Teriflunomide (Aubagio®) in Participants With Relapsing Forms of Multiple Sclerosis NCT04410991 CTgov 临床3期 复发性多发性硬化 899 Tolebrutinib(Tolebrutinib 60 mg) Annualized Relapse Rate (ARR) as Assessed by Confirmed Protocol-defined Adjudicated Relapses = 0.108 relapses per participant year (95%CI, 0.089 ~ 0.131) - 2025-06-18 Sanofi 托莱布替尼 https://clinicaltrials.gov/ct2/show/results/NCT04410991 https://synapse.zhihuiya.com/clinical-result-detail/e23e3a42323d22a53223aa0422482855 Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis NCT04411641 Pubmed 临床3期 继发进展型多发性硬化 1131 Tolebrutinib 60 mg once daily SAE = 15.0 %  积极 2025-05-15 Sanofi 托莱布替尼 https://pubmed.ncbi.nlm.nih.gov/40202696/ | https://doi.org/10.1056/nejmoa2415988 https://synapse.zhihuiya.com/clinical-result-detail/3e22028925a888a52224a2d5d5528253 Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis NCT04411641 Pubmed 临床3期 继发进展型多发性硬化 1131 Placebo SAE = 10.4 %  积极 2025-05-15 Sanofi 托莱布替尼 https://pubmed.ncbi.nlm.nih.gov/40202696/ | https://doi.org/10.1056/nejmoa2415988 https://synapse.zhihuiya.com/clinical-result-detail/3e22028925a888a52224a2d5d5528253 LONG-TERM OUTCOMES IN WALDENSTRÖM MACROGLOBULINEMIA (WM) PATIENTS WHO DISCONTINUE BRUTON'S TYROSINE KINASE INHIBITOR (BTKI) THERAPY - EHA N/A 巨球蛋白血症 153 BTKi Adverse Event: AE = AEs leading to therapy discontinuation were reported in 44% of patients who discontinued 1st BTKi therapy   - 2025-05-14 MD Anderson Cancer Center Orlando - https://library.ehaweb.org/eha/2025/eha2025-congress/4160964/karan.chohan.long-term.outcomes.in.waldenstrm.macroglobulinemia.28wm29.patients.html https://synapse.zhihuiya.com/clinical-result-detail/208240a8e89254aa20a22ee38e22592e LONG-TERM OUTCOMES IN WALDENSTRÖM MACROGLOBULINEMIA (WM) PATIENTS WHO DISCONTINUE BRUTON'S TYROSINE KINASE INHIBITOR (BTKI) THERAPY - EHA N/A 巨球蛋白血症 153 Alternate BTKi-based regimen Adverse Event: AE = AEs leading to therapy discontinuation were reported in 44% of patients who discontinued 1st BTKi therapy   - 2025-05-14 MD Anderson Cancer Center Orlando - https://library.ehaweb.org/eha/2025/eha2025-congress/4160964/karan.chohan.long-term.outcomes.in.waldenstrm.macroglobulinemia.28wm29.patients.html https://synapse.zhihuiya.com/clinical-result-detail/208240a8e89254aa20a22ee38e22592e Tolebrutinib versus Teriflunomide in Relapsing Multiple Sclerosis NCT04410991 | NCT04410978 Pubmed 临床3期 复发性多发性硬化 - Tolebrutinib 60 mg once dailyTolebrutinib 60 mg once dailyTolebrutinib 60 mg once daily ARR(GEMINI 1) = 0.13 Unit  不佳 2025-04-08 Sanofi 托莱布替尼 https://pubmed.ncbi.nlm.nih.gov/40202623/ | https://doi.org/10.1056/nejmoa2415985 https://synapse.zhihuiya.com/clinical-result-detail/ee2e48dd088d98eee2e8e28590d2dd3a Tolebrutinib versus Teriflunomide in Relapsing Multiple Sclerosis NCT04410991 | NCT04410978 Pubmed 临床3期 复发性多发性硬化 - Teriflunomide 14 mg once daily ARR(GEMINI 1) = 0.12 Unit  不佳 2025-04-08 Sanofi 托莱布替尼 https://pubmed.ncbi.nlm.nih.gov/40202623/ | https://doi.org/10.1056/nejmoa2415985 https://synapse.zhihuiya.com/clinical-result-detail/ee2e48dd088d98eee2e8e28590d2dd3a 4392Clinical Outcomes of Lymphoplasmacytic Lymphoma / Waldenstrom Macroglobulinemia (LPL/WM) in the Targeted Therapy Era: A US Multicenter Retrospective Analysis - ASH N/A 淋巴浆细胞性淋巴瘤 | 巨球蛋白血症 - Chemo-immunotherapy (CIT) ORR = 68 %  - 2024-12-09 University of Arkansas for Medical Sciences | The Ohio State University | Hematology/Oncology Associates of Central New York PC | Taussig Cancer Institute | H. Lee Moffitt Cancer Center & Research Institute, Inc. | The Fox Chase Cancer Center | Roswell Park Comprehensive Cancer Center - https://ash.confex.com/ash/2024/webprogram/Paper199278.html https://synapse.zhihuiya.com/clinical-result-detail/e95288a9eeee22482e8d2ee54345ea54 4392Clinical Outcomes of Lymphoplasmacytic Lymphoma / Waldenstrom Macroglobulinemia (LPL/WM) in the Targeted Therapy Era: A US Multicenter Retrospective Analysis - ASH N/A 淋巴浆细胞性淋巴瘤 | 巨球蛋白血症 - Rituximab (R) ORR = 34 %  - 2024-12-09 University of Arkansas for Medical Sciences | The Ohio State University | Hematology/Oncology Associates of Central New York PC | Taussig Cancer Institute | H. Lee Moffitt Cancer Center & Research Institute, Inc. | The Fox Chase Cancer Center | Roswell Park Comprehensive Cancer Center - https://ash.confex.com/ash/2024/webprogram/Paper199278.html https://synapse.zhihuiya.com/clinical-result-detail/e95288a9eeee22482e8d2ee54345ea54 5109Real-World Risk of Major Bleeding Events in BTKi-Treated Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL) - ASH N/A 慢性淋巴细胞白血病 | 小淋巴细胞淋巴瘤 - BTKi 大出血 = 6.5 %  - 2024-12-09 AstraZeneca AS | University of Pittsburgh Medical Center | AstraZeneca, Inc. | AstraZeneca PLC 托莱布替尼 https://ash.confex.com/ash/2024/webprogram/Paper198681.html https://synapse.zhihuiya.com/clinical-result-detail/ae2d228884d5da5ad4e4e5ea202205aa 5109Real-World Risk of Major Bleeding Events in BTKi-Treated Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL) - ASH N/A 慢性淋巴细胞白血病 | 小淋巴细胞淋巴瘤 - Anticoagulant/Antiplatelet 大出血 = 5.2 %  - 2024-12-09 AstraZeneca AS | University of Pittsburgh Medical Center | AstraZeneca, Inc. | AstraZeneca PLC 托莱布替尼 https://ash.confex.com/ash/2024/webprogram/Paper198681.html https://synapse.zhihuiya.com/clinical-result-detail/ae2d228884d5da5ad4e4e5ea202205aa 5105Real-World Bleeding Risk, Outcomes and Treatment Patterns of Patients with CLL/SLL Receiving BTKi with or without Prescription Anticoagulants or Antiplatelets - ASH N/A 小淋巴细胞淋巴瘤 - BTKi (Ibrutinib) Adverse Event: Bleeding events = A quarter of all pts experienced a non-fatal bleed, resulting in <15% of the pts discontinuing and >50% pts interrupting their BTKi tx   - 2024-12-09 AstraZeneca AS | University of Pittsburgh Medical Center 托莱布替尼 https://ash.confex.com/ash/2024/webprogram/Paper198724.html https://synapse.zhihuiya.com/clinical-result-detail/ae58994a2802282ea9438ea3a3e3558d 5105Real-World Bleeding Risk, Outcomes and Treatment Patterns of Patients with CLL/SLL Receiving BTKi with or without Prescription Anticoagulants or Antiplatelets - ASH N/A 小淋巴细胞淋巴瘤 - Prescription Anticoagulants or Antiplatelets Adverse Event: Bleeding events = A quarter of all pts experienced a non-fatal bleed, resulting in <15% of the pts discontinuing and >50% pts interrupting their BTKi tx   - 2024-12-09 AstraZeneca AS | University of Pittsburgh Medical Center 托莱布替尼 https://ash.confex.com/ash/2024/webprogram/Paper198724.html https://synapse.zhihuiya.com/clinical-result-detail/ae58994a2802282ea9438ea3a3e3558d 1654Real World Treatment Outcomes in the First Line Management of Waldenström Macroglobulinemia from the Global Patient Derived Data Registry, Whimsical - ASH N/A 巨球蛋白血症 - Bendamustine and Rituximab (BR) TTNT = not reached Year  - 2024-12-07 The University of Texas MD Anderson Cancer Center | Cancer Center | Concord Repatriation General Hospital | University College London Hospitals NHS Foundation Trust | Brown University - https://ash.confex.com/ash/2024/webprogram/Paper202820.html https://synapse.zhihuiya.com/clinical-result-detail/902a52ddde822294e850e4222250e34e 1654Real World Treatment Outcomes in the First Line Management of Waldenström Macroglobulinemia from the Global Patient Derived Data Registry, Whimsical - ASH N/A 巨球蛋白血症 - Bruton Tyrosine-Kinase inhibitors (BTKi) TTNT = 8.9 Year  - 2024-12-07 The University of Texas MD Anderson Cancer Center | Cancer Center | Concord Repatriation General Hospital | University College London Hospitals NHS Foundation Trust | Brown University - https://ash.confex.com/ash/2024/webprogram/Paper202820.html https://synapse.zhihuiya.com/clinical-result-detail/902a52ddde822294e850e4222250e34e Tolebrutinib demonstrated a 31% delay in time to onset of confirmed disability progression in non-relapsing secondary progressive multiple sclerosis phase 3 study NCT04410978，NCT04410991 - - 多发性硬化症 1872 Tolebrutinib 复合终点 = 0.12   不佳 2024-09-20 Sanofi 托莱布替尼 https://pipelinereview.com/tolebrutinib-demonstrated-a-31-delay-in-time-to-onset-of-confirmed-disability-progression-in-non-relapsing-secondary-progressive-multiple-sclerosis-phase-3-study/ https://synapse.zhihuiya.com/clinical-result-detail/0a2da8292ed452e4835202e5552a38e2 Tolebrutinib demonstrated a 31% delay in time to onset of confirmed disability progression in non-relapsing secondary progressive multiple sclerosis phase 3 study NCT04410978，NCT04410991 - - 多发性硬化症 1872 特立氟胺 复合终点 = 0.12   不佳 2024-09-20 Sanofi 托莱布替尼 https://pipelinereview.com/tolebrutinib-demonstrated-a-31-delay-in-time-to-onset-of-confirmed-disability-progression-in-non-relapsing-secondary-progressive-multiple-sclerosis-phase-3-study/ https://synapse.zhihuiya.com/clinical-result-detail/0a2da8292ed452e4835202e5552a38e2 CLL-495 Treatment Characteristics and Outcomes of Patients With Chronic/Small Lymphocytic Leukemia (CLL) Treated With Venetoclax and Bruton Tyrosine Kinase Inhibitor (BTKi) Combination Therapies - SOHO N/A 慢性淋巴细胞白血病 - Venetoclax+BTKi ORR = 90.4 %  - 2024-09-04 Analysis Group, Inc. | Nottingham University Hospitals Nhs Trust | AbbVie, Inc. 维奈克拉 https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)01287-4/fulltext https://synapse.zhihuiya.com/clinical-result-detail/ee229de282da3052eee92e5a5e52a248 CLL-495 Treatment Characteristics and Outcomes of Patients With Chronic/Small Lymphocytic Leukemia (CLL) Treated With Venetoclax and Bruton Tyrosine Kinase Inhibitor (BTKi) Combination Therapies - SOHO N/A 慢性淋巴细胞白血病 - Venetoclax+ibrutinib-based ORR = 94.9 %  - 2024-09-04 Analysis Group, Inc. | Nottingham University Hospitals Nhs Trust | AbbVie, Inc. 维奈克拉 https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)01287-4/fulltext https://synapse.zhihuiya.com/clinical-result-detail/ee229de282da3052eee92e5a5e52a248 Sanofi’s investigational BTK inhibitor tolebrutinib shows promise in phase 3 MS study NCT04411641 NEWS 临床3期 继发进展型多发性硬化 - Tolebrutinib CDP: HR = 0.69(95% CI, 0.55 ~ 0.88), P-Value = 0.0026 达到 积极 2024-09-02 Sanofi 托莱布替尼 https://pmlive.com/pharma_news/sanofis-investigational-btk-inhibitor-tolebrutinib-shows-promise-in-phase-3-ms-study/ https://synapse.zhihuiya.com/clinical-result-detail/8a8e5245402e280e3a52053a35dd55d2 Sanofi’s investigational BTK inhibitor tolebrutinib shows promise in phase 3 MS study NCT04411641 NEWS 临床3期 继发进展型多发性硬化 - placebo CDP: HR = 0.69(95% CI, 0.55 ~ 0.88), P-Value = 0.0026 达到 积极 2024-09-02 Sanofi 托莱布替尼 https://pmlive.com/pharma_news/sanofis-investigational-btk-inhibitor-tolebrutinib-shows-promise-in-phase-3-ms-study/ https://synapse.zhihuiya.com/clinical-result-detail/8a8e5245402e280e3a52053a35dd55d2 Real-world risk of bleeding events in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) treated with BTKi. - ASCO N/A 慢性淋巴细胞白血病 2091 Ibrutinib 出血 = 26.6 %  积极 2024-05-24 AstraZeneca PLC 托莱布替尼 https://meetings.asco.org/abstracts-presentations/239180 https://synapse.zhihuiya.com/clinical-result-detail/5d02988ea5382a850202d22ae4052d45 Real-world risk of bleeding events in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) treated with BTKi. - ASCO N/A 慢性淋巴细胞白血病 2091 Acalabrutinib 出血 = 26.6 %  积极 2024-05-24 AstraZeneca PLC 托莱布替尼 https://meetings.asco.org/abstracts-presentations/239180 https://synapse.zhihuiya.com/clinical-result-detail/5d02988ea5382a850202d22ae4052d45 REAL-WORLD FIRST LINE CHRONIC LYMPHOCYTIC LEUKEMIA TREATMENT IN GERMANY IN THE ERA OF TARGETED AGENTS - EHA N/A 慢性淋巴细胞白血病 481 BTKi-based treatment Aberration of TP53 = 29% %  - 2024-05-14 - - https://library.ehaweb.org/eha/2024/eha2024-congress/419932/zuzana.dostalova.real-world.first.line.chronic.lymphocytic.leukemia.treatment.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2552%2Aot_id%3D29194%2Amarker%3D5100%2Afeatured%3D18527 https://synapse.zhihuiya.com/clinical-result-detail/0588589a22a92455a42e222a205e5852 REAL-WORLD FIRST LINE CHRONIC LYMPHOCYTIC LEUKEMIA TREATMENT IN GERMANY IN THE ERA OF TARGETED AGENTS - EHA N/A 慢性淋巴细胞白血病 481 VEN-based treatment Aberration of TP53 = 29% %  - 2024-05-14 - - https://library.ehaweb.org/eha/2024/eha2024-congress/419932/zuzana.dostalova.real-world.first.line.chronic.lymphocytic.leukemia.treatment.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2552%2Aot_id%3D29194%2Amarker%3D5100%2Afeatured%3D18527 https://synapse.zhihuiya.com/clinical-result-detail/0588589a22a92455a42e222a205e5852 TIME TO NEXT TREATMENT AFTER FIRST-LINE TREATMENT WITH TIME-LIMITED TARGETED AGENTS: A POOLED ANALYSIS OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA TREATED WITHIN CLINICAL TRIALS OF THE GCLLSG - EHA N/A 慢性淋巴细胞白血病 - anti-CD20+BCL2i-based regimen Median TTNT = not reached Month  积极 2024-05-14 - - https://library.ehaweb.org/eha/2024/eha2024-congress/420722/nadine.kutsch.time.to.next.treatment.after.first-line.treatment.with.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2552%2Aot_id%3D29194%2Amarker%3D5101%2Afeatured%3D18527 https://synapse.zhihuiya.com/clinical-result-detail/29820558a2d5e255ea02a5aa5582a5a9 TIME TO NEXT TREATMENT AFTER FIRST-LINE TREATMENT WITH TIME-LIMITED TARGETED AGENTS: A POOLED ANALYSIS OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA TREATED WITHIN CLINICAL TRIALS OF THE GCLLSG - EHA N/A 慢性淋巴细胞白血病 - anti-CD20+BTKi-based regimen Median TTNT = not reached Month  积极 2024-05-14 - - https://library.ehaweb.org/eha/2024/eha2024-congress/420722/nadine.kutsch.time.to.next.treatment.after.first-line.treatment.with.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2552%2Aot_id%3D29194%2Amarker%3D5101%2Afeatured%3D18527 https://synapse.zhihuiya.com/clinical-result-detail/29820558a2d5e255ea02a5aa5582a5a9 A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Tolebrutinib (SAR442168) in Adults With Generalized Myasthenia Gravis (MG) NCT05132569 CTgov 临床3期 重症肌无力 6 placebo+tolebrutinib(DB Period: Placebo) DB Period: Change From Baseline in Quantitative Myasthenia Gravis (QMG) Total Score at Week 12(Mean) = -2.0 Point  - 2024-04-08 Sanofi 托莱布替尼 https://clinicaltrials.gov/ct2/show/results/NCT05132569 https://synapse.zhihuiya.com/clinical-result-detail/99aa223ad23aa2ea942de2dade2e09d2 A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Tolebrutinib (SAR442168) in Adults With Generalized Myasthenia Gravis (MG) NCT05132569 CTgov 临床3期 重症肌无力 6 Tolebrutinib(DB Period: Tolebrutinib) DB Period: Change From Baseline in Quantitative Myasthenia Gravis (QMG) Total Score at Week 12(Mean) = -1.7 Point  - 2024-04-08 Sanofi 托莱布替尼 https://clinicaltrials.gov/ct2/show/results/NCT05132569 https://synapse.zhihuiya.com/clinical-result-detail/99aa223ad23aa2ea942de2dade2e09d2 4644  Outcomes and Treatment Sequences of Therapies with BCL2- and BTK Inhibitors in Chronic Lymphocytic Leukemia (CLL): An Analysis of Patient Data within the German CLL Study Group (GCLLSG) Registry - ASH N/A 慢性淋巴细胞白血病 - Venetoclax-based regimen mEFS = 31.8 Month  - 2023-12-11 - - https://ash.confex.com/ash/2023/webprogram/Paper185741.html https://synapse.zhihuiya.com/clinical-result-detail/2d85825de834832ed0d544455aa28a32 4644  Outcomes and Treatment Sequences of Therapies with BCL2- and BTK Inhibitors in Chronic Lymphocytic Leukemia (CLL): An Analysis of Patient Data within the German CLL Study Group (GCLLSG) Registry - ASH N/A 慢性淋巴细胞白血病 - BTKi-based regimen mEFS = 23.2 Month  - 2023-12-11 - - https://ash.confex.com/ash/2023/webprogram/Paper185741.html https://synapse.zhihuiya.com/clinical-result-detail/2d85825de834832ed0d544455aa28a32 3276  Clinical Outcomes with Venetoclax-Based Treatment Regimens in Patients with Chronic Lymphocytic Leukemia (CLL) - ASH N/A 慢性淋巴细胞白血病 155 First-line therapy with venetoclax + obinutuzumab mOS = 54.6 Month  - 2023-12-10 Mayo Clinic 维奈克拉 https://ash.confex.com/ash/2023/webprogram/Paper183007.html https://synapse.zhihuiya.com/clinical-result-detail/20aee328ae580a2a23a890d2425ed528 3276  Clinical Outcomes with Venetoclax-Based Treatment Regimens in Patients with Chronic Lymphocytic Leukemia (CLL) - ASH N/A 慢性淋巴细胞白血病 155 Relapsed/BTKi-naïve venetoclax-treated patients Median TFS = 26.9 Month  - 2023-12-10 Mayo Clinic 维奈克拉 https://ash.confex.com/ash/2023/webprogram/Paper183007.html https://synapse.zhihuiya.com/clinical-result-detail/20aee328ae580a2a23a890d2425ed528 1678  Impact of the Current Treatments on the Survival of Patients with Mantle Cell Lymphoma (MCL): A Real-Life Study on Behalf of the Spanish Group of Lymphoma (GELTAMO) - ASH N/A 套细胞淋巴瘤 505 HiDAC (high-dose cytarabine or HiDAC-based) CR = 78.4 %  - 2023-12-09 - - https://ash.confex.com/ash/2023/webprogram/Paper186101.html https://synapse.zhihuiya.com/clinical-result-detail/a5ad0eda59489822898a2a80ae225a45 1678  Impact of the Current Treatments on the Survival of Patients with Mantle Cell Lymphoma (MCL): A Real-Life Study on Behalf of the Spanish Group of Lymphoma (GELTAMO) - ASH N/A 套细胞淋巴瘤 505 BTKi (BTK inhibitors) CR/CRh = 60.8 %  - 2023-12-09 - - https://ash.confex.com/ash/2023/webprogram/Paper186101.html https://synapse.zhihuiya.com/clinical-result-detail/a5ad0eda59489822898a2a80ae225a45 1907  Comparison of Venetoclax Based Treatments for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia - ASH N/A 慢性淋巴细胞白血病 98 Venetoclax monotherapy MRD = 66.7 %  - 2023-12-09 - 维奈克拉 https://ash.confex.com/ash/2023/webprogram/Paper188129.html https://synapse.zhihuiya.com/clinical-result-detail/22d2028849855a534e3e922e9282828e 1907  Comparison of Venetoclax Based Treatments for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia - ASH N/A 慢性淋巴细胞白血病 98 Venetoclax + rituximab MRD = 82.4 %  - 2023-12-09 - 维奈克拉 https://ash.confex.com/ash/2023/webprogram/Paper188129.html https://synapse.zhihuiya.com/clinical-result-detail/22d2028849855a534e3e922e9282828e MRI Outcomes from the Long-term Extension Study of Tolebrutinib in Participants with Relapsing Multiple Sclerosis: 3-Year Results NCT03996291 ECTRIMS 临床2期 复发性多发性硬化 125 5/60 mg New Gd-enhancing T1 lesions = 0.5 count  - 2023-09-30 Sanofi 托莱布替尼 https://journals.sagepub.com/doi/epub/10.1177/13524585231196194 https://synapse.zhihuiya.com/clinical-result-detail/28229353ead20de54e550ad805d24a52 MRI Outcomes from the Long-term Extension Study of Tolebrutinib in Participants with Relapsing Multiple Sclerosis: 3-Year Results NCT03996291 ECTRIMS 临床2期 复发性多发性硬化 125 15/60 mg New Gd-enhancing T1 lesions = 0.48 count  - 2023-09-30 Sanofi 托莱布替尼 https://journals.sagepub.com/doi/epub/10.1177/13524585231196194 https://synapse.zhihuiya.com/clinical-result-detail/28229353ead20de54e550ad805d24a52 Baseline Characteristics in the Tolebrutinib Phase 3 Non-Relapsing Secondary Progressive Multiple Sclerosis (nrSPMS) HERCULES Clinical Trial NCT04411641 ECTRIMS 临床3期 继发进展型多发性硬化 - Tolebrutinib 60 mg T2 lesion volume = 18.8 cm3 (mean±SD, 14.4) - 2023-09-30 Sanofi 托莱布替尼 https://journals.sagepub.com/doi/epub/10.1177/13524585231196195 https://synapse.zhihuiya.com/clinical-result-detail/e0204828248a85582aae98583a5a45a8 Baseline Characteristics in theTolebrutinib Phase 3 Relapsing MultipleSclerosis GEMINI 1 and 2 Trials NCT04410978 | NCT04410991 EAN 临床3期 复发性多发性硬化 - Tolebrutinib 60 mg Time since diagnosis = 4.7 Year  积极 2023-06-28 Sanofi 托莱布替尼 https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.15950 https://synapse.zhihuiya.com/clinical-result-detail/8422e4a8e55e8232a22a22eedad82a29 Baseline Characteristics in theTolebrutinib Phase 3 Relapsing MultipleSclerosis GEMINI 1 and 2 Trials NCT04410978 | NCT04410991 EAN 临床3期 复发性多发性硬化 - Teriflunomide 14 mg Time since diagnosis = 3.8 Year  积极 2023-06-28 Sanofi 托莱布替尼 https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.15950 https://synapse.zhihuiya.com/clinical-result-detail/8422e4a8e55e8232a22a22eedad82a29 HARNESSING BTKI THERAPY BY CDK4/6I CONTROL OF T CELL SURVEILLANCE - ICML 临床1期 - 27 Palbociclib CR rate = 42 %  积极 2023-06-09 Weill Cornell Medicine 托莱布替尼 https://onlinelibrary.wiley.com/doi/10.1002/hon.3163_120 https://synapse.zhihuiya.com/clinical-result-detail/ee22d38228a528e485a55e8ea59a8da8 REAL-WORLD TREATMENT AND OUTCOMES OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) RECEIVING FIRST-LINE (1L) THERAPY IN THE NOVEL AGENT ERA: AN INTERNATIONAL STUDY - EHA N/A - - Anti-CD20 monotherapy mPFS = 23 Month  - 2023-06-08 - - - https://synapse.zhihuiya.com/clinical-result-detail/8842e52d8eedde0502e9a28d8e540e03 REAL-WORLD TREATMENT AND OUTCOMES OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) RECEIVING FIRST-LINE (1L) THERAPY IN THE NOVEL AGENT ERA: AN INTERNATIONAL STUDY - EHA N/A - - BTKi-based therapy mPFS = 51 Month  - 2023-06-08 - - - https://synapse.zhihuiya.com/clinical-result-detail/8842e52d8eedde0502e9a28d8e540e03 Safety and Clinical Efficacy Outcomes From the Long-term Extension Study of Tolebrutinib in Participants With Relapsing Multiple Sclerosis: 2.5-Year Results (S16.010) NCT03889639 AAN 临床2期 复发性多发性硬化 107 Tolebrutinib 60 mg/day Adverse Event: COVID-19 = 24.8% [31/125]   积极 2023-04-25 Sanofi 托莱布替尼 https://www.neurology.org/doi/full/10.1212/WNL.0000000000202287 https://synapse.zhihuiya.com/clinical-result-detail/80e020050a3e882323ea35d45d2de228 Comparative CNS Pharmacology of Tolebrutinib Versus Other BTK Inhibitor Candidates for Treating MS (S46.007) - AAN 临床3期 多发性硬化症 - Tolebrutinib CSF exposure = 4.8 ng/mL (kp, uu CSF, 0.40) 积极 2023-04-25 TMed Holdings, Inc. | Neurology First | Bcb Ltd 托莱布替尼 https://www.neurology.org/doi/full/10.1212/WNL.0000000000203897 https://synapse.zhihuiya.com/clinical-result-detail/929ea348544e555a3a2982e4a2492285 Comparative CNS Pharmacology of Tolebrutinib Versus Other BTK Inhibitor Candidates for Treating MS (S46.007) - AAN 临床3期 多发性硬化症 - Evobrutinib CSF exposure = 3.2 ng/mL (kp, uu CSF, 0.13) 积极 2023-04-25 TMed Holdings, Inc. | Neurology First | Bcb Ltd 托莱布替尼 https://www.neurology.org/doi/full/10.1212/WNL.0000000000203897 https://synapse.zhihuiya.com/clinical-result-detail/929ea348544e555a3a2982e4a2492285 MRI, Efficacy, and Safety of Tolebrutinib in Patients with Highly Active Disease (HAD): 2-Year Data from the Phase 2b Long-term Safety (LTS) Study (P6-3.017) NCT03889639 AAN 临床2期 - 61 Tolebrutinib 60mg Adverse Event: TEAEs = Most common treatment-emergent adverse events (TEAEs) were COVID-19, nasopharyngitis, headache, and upper respiratory tract infection   - 2023-04-25 Sanofi 托莱布替尼 https://www.neurology.org/doi/full/10.1212/WNL.0000000000202143 https://synapse.zhihuiya.com/clinical-result-detail/40929aad5a23ea95558220e2a39ee5de MRI outcomes from the long-term extension study of tolebrutinib in patients with relapsing multiple sclerosis: 2-year results NCT03889639 ECTRIMS 临床2期 复发性多发性硬化 125 Tolebrutinib 5 mg/day T2 lesion volume change = 0.38 cm3  积极 2022-10-12 Sanofi 托莱布替尼 https://journals.sagepub.com/doi/epub/10.1177/13524585221123687 https://synapse.zhihuiya.com/clinical-result-detail/932de853229ae0a5389d3e88e9a4a552 MRI, efficacy, and safety of tolebrutinib in patients with highly active disease (HAD): 2-year data from the phase 2b Long-term safety (LTS) Study NCT03889639 ECTRIMS 临床2期 - 61 Tolebrutinib 60 mg/day Adverse Event: COVID-19 = 20%   - 2022-10-12 Sanofi 托莱布替尼 https://journals.sagepub.com/doi/epub/10.1177/13524585221123687 https://synapse.zhihuiya.com/clinical-result-detail/983dd55498e29ae32d08a5a2ea909583 CLL-461 Humoral Response to COVID-19 Vaccine: A Challenge in CLL - SOHO N/A 新型冠状病毒感染 | 慢性淋巴细胞白血病 - Patients on active therapy SCR = 20.5 %  - 2022-10-01 Laboratories at Bonfils Clinical Laboratory, Inc. - https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(22)01348-9/fulltext https://synapse.zhihuiya.com/clinical-result-detail/aad82980a92e2d02e828d8d2959e5ee2 CLL-461 Humoral Response to COVID-19 Vaccine: A Challenge in CLL - SOHO N/A 新型冠状病毒感染 | 慢性淋巴细胞白血病 - BTKi treatment Antibody response rate = 19.7 %  - 2022-10-01 Laboratories at Bonfils Clinical Laboratory, Inc. - https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(22)01348-9/fulltext https://synapse.zhihuiya.com/clinical-result-detail/aad82980a92e2d02e828d8d2959e5ee2 CLL-105 Cumulative Incidence of Grade 3 or Higher Infections in Patients With CLL/SLL Treated With BTKi-Based Regimens - SOHO N/A 小淋巴细胞淋巴瘤 - BTKi-based regimens Grade 3 or higher infections = 19.86 % ( 16.03 ~ 23.98) - 2022-10-01 - 伊布替尼 | 阿可替尼 | 泽布替尼 https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(22)01321-0/fulltext https://synapse.zhihuiya.com/clinical-result-detail/d558930482d2a934a802255322405292 CLL-105 Cumulative Incidence of Grade 3 or Higher Infections in Patients With CLL/SLL Treated With BTKi-Based Regimens - SOHO N/A 小淋巴细胞淋巴瘤 - Monotherapy with BTKi Grade 3 or higher infections = 20.7 % ( 16.48 ~ 25.26) - 2022-10-01 - 伊布替尼 | 阿可替尼 | 泽布替尼 https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(22)01321-0/fulltext https://synapse.zhihuiya.com/clinical-result-detail/d558930482d2a934a802255322405292 Characteristics and Outcomes of COVID-19 Cases from the Long-term Extension Study of Tolebrutinib in Patients with Relapsing MS NCT03996291 ACTRIMS 临床2期 新型冠状病毒感染 | 复发性多发性硬化 130 Tolebrutinib Adverse Event: COVID-19 cases = COVID-19 cases were mild (n=11) or moderate (n=9). Three of the moderate COVID-19 cases were considered serious, of which 2 were hospitalized (female aged 55 years and male aged 57 years). All patients recovered (one patient was still recovering at cut-off), and all patients remained in the study. Tolebrutinib was interrupted temporarily in 4 patients while the remaining 16 patients continued tolebrutinib uninterrupted during their infection. Only 1 fully vaccinated patient (female, aged 56 years; vaccinated with BNT162b2) contracted COVID-19.   积极 2022-05-16 Sanofi 托莱布替尼 https://journals.sagepub.com/doi/full/10.1177/13524585221094745 https://synapse.zhihuiya.com/clinical-result-detail/e828a5d9220aa228ee2282e5853955a9 MRI, Safety, and Efficacy Outcomes in Patients with Relapsing MS: 18-month Results from the Long-term Extension Study of Tolebrutinib NCT03889639 ACTRIMS 临床2期 复发性多发性硬化 129 Tolebrutinib 5 mg/day Adverse Event: COVID-19 = 12.8% [16/125]   积极 2022-05-16 Sanofi 托莱布替尼 https://journals.sagepub.com/doi/full/10.1177/13524585221094745 https://synapse.zhihuiya.com/clinical-result-detail/28a5e9d022a2e00442d309e08e485858 MRI, Safety, and Efficacy Outcomes in Patients with Relapsing MS: 18-month Results from the Long-term Extension Study of Tolebrutinib NCT03889639 ACTRIMS 临床2期 复发性多发性硬化 129 Tolebrutinib 15 mg/day Adverse Event: COVID-19 = 12.8% [16/125]   积极 2022-05-16 Sanofi 托莱布替尼 https://journals.sagepub.com/doi/full/10.1177/13524585221094745 https://synapse.zhihuiya.com/clinical-result-detail/28a5e9d022a2e00442d309e08e485858 TREATMENT SEQUENCES AND OUTCOMES OF PATIENTS WITH CLL TREATED WITH TARGETED AGENTS IN REAL-WORLD SETTINGS - EHA N/A 慢性淋巴细胞白血病 - 1L CT/CIT 1L tx use = 48.8 %  - 2022-05-12 Analysis Group, Inc. | Nottingham University Hospitals Nhs Trust | AbbVie, Inc. - https://library.ehaweb.org/eha/2022/eha2022-congress/357533/anthony.r.mato.treatment.sequences.and.outcomes.of.patients.with.cll.treated.html https://synapse.zhihuiya.com/clinical-result-detail/4e0a52e2ed453a28d2a3520e0a40a355 TREATMENT SEQUENCES AND OUTCOMES OF PATIENTS WITH CLL TREATED WITH TARGETED AGENTS IN REAL-WORLD SETTINGS - EHA N/A 慢性淋巴细胞白血病 - 1L targeted agent 1L tx use = 40.6 %  - 2022-05-12 Analysis Group, Inc. | Nottingham University Hospitals Nhs Trust | AbbVie, Inc. - https://library.ehaweb.org/eha/2022/eha2022-congress/357533/anthony.r.mato.treatment.sequences.and.outcomes.of.patients.with.cll.treated.html https://synapse.zhihuiya.com/clinical-result-detail/4e0a52e2ed453a28d2a3520e0a40a355 MRI Outcomes from the Long-term Extension Study of Tolebrutinib in Patients with Relapsing Multiple Sclerosis: 18-Month Results (P1-1.Virtual) NCT03996291 AAN 临床2期 复发性多发性硬化 125 Tolebrutinib 5 mg SEL volume = 441 mm^3 ( 69 ~ 630) 积极 2022-05-03 Sanofi 托莱布替尼 https://www.neurology.org/doi/full/10.1212/WNL.98.18_supplement.2577 https://synapse.zhihuiya.com/clinical-result-detail/52905d302a222e982a83223e5e505ee3 MRI Outcomes from the Long-term Extension Study of Tolebrutinib in Patients with Relapsing Multiple Sclerosis: 18-Month Results (P1-1.Virtual) NCT03996291 AAN 临床2期 复发性多发性硬化 125 Tolebrutinib 15 mg SEL volume = 468 mm^3 ( 102 ~ 1317) 积极 2022-05-03 Sanofi 托莱布替尼 https://www.neurology.org/doi/full/10.1212/WNL.98.18_supplement.2577 https://synapse.zhihuiya.com/clinical-result-detail/52905d302a222e982a83223e5e505ee3 New long-term data reinforcing promising safety and efficacy profile of brain-penetrant tolebrutinib presented at ECTRIMS 2021  NCT03996291 GlobeNewswire 临床2期 多发性硬化症 125 Tolebrutinib ARR(treated with 60mg) = 0.17 Point (95%CI, 0.10 ~ 0.29) 积极 2021-10-13 Sanofi 托莱布替尼 https://www.globenewswire.com/news-release/2021/10/13/2313117/0/en/New-long-term-data-reinforcing-promising-safety-and-efficacy-profile-of-brain-penetrant-tolebrutinib-presented-at-ECTRIMS-2021.html https://synapse.zhihuiya.com/clinical-result-detail/23ee208333242e22285252e0458305e4 MCL-041: Outcomes for Recurrent Mantle Cell Lymphoma Post-BTK Inhibitor Therapy in Japan: An Administrative Database Study - SOHO N/A 复发性套细胞淋巴瘤 - Post-BTKi Therapy Adverse Event: anti-infectives = 52% vs 32%   - 2021-09-01 Eli Lilly & Co. | Kindai University Faculty of Medicine | Eli Lilly Japan KK - https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(21)01918-2/fulltext https://synapse.zhihuiya.com/clinical-result-detail/8e0de82888a05882a55ed2a3e34e5852 Efficacy and Safety of Tolebrutinib in Patients With Highly Active Relapsing MS: Subgroup Analysis of the Phase 2b Study (2260) NCT03889639 AAN 临床2期 复发性多发性硬化 130 Tolebrutinib 5 mg New Gd-enhancing lesions = 0.82 Lesion  - 2021-04-13 Sanofi 托莱布替尼 https://www.neurology.org/doi/full/10.1212/WNL.96.15_supplement.2260 https://synapse.zhihuiya.com/clinical-result-detail/2503e0328aee0352254a89adae90d898 Efficacy and Safety of Tolebrutinib in Patients With Highly Active Relapsing MS: Subgroup Analysis of the Phase 2b Study (2260) NCT03889639 AAN 临床2期 复发性多发性硬化 130 Tolebrutinib 15 mg New Gd-enhancing lesions = 0.5 Lesion  - 2021-04-13 Sanofi 托莱布替尼 https://www.neurology.org/doi/full/10.1212/WNL.96.15_supplement.2260 https://synapse.zhihuiya.com/clinical-result-detail/2503e0328aee0352254a89adae90d898 Efficacy and safety outcomes in patientswith relapsing forms of MS treatedwith the CNS-Penetrating BTK inhibitorSAR442168: results from thephase 2b trial NCT03889639 EAN 临床2期 复发-缓解型多发性硬化 130 SAR442168 5mg Time since MS diagnosis = 5.6 Year  - 2020-05-22 Sanofi 托莱布替尼 https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.14306 https://synapse.zhihuiya.com/clinical-result-detail/e2ade43e28d985025034e8044a222da5 Efficacy and safety outcomes in patientswith relapsing forms of MS treatedwith the CNS-Penetrating BTK inhibitorSAR442168: results from thephase 2b trial NCT03889639 EAN 临床2期 复发-缓解型多发性硬化 130 SAR442168 15mg Time since MS diagnosis = 5.6 Year  - 2020-05-22 Sanofi 托莱布替尼 https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.14306 https://synapse.zhihuiya.com/clinical-result-detail/e2ade43e28d985025034e8044a222da5