Tolebrutinib

BTK抑制剂的出现，让很多CLL/SLL、套细胞淋巴瘤、边缘区淋巴瘤患者获得了显著的疾病控制。但在长期用药过程中，一部分患者因为副作用无法耐受而被迫停药，也有一部分患者始终对BTK抑制剂反应不佳，或者治疗后出现进展。既然BTK这条路走不通或不耐受，下一步还有别的选择吗？BCL-2抑制剂就是一条不同机制的靶向通路。 ICP-248是一款新型口服高选择性BCL-2抑制剂，目前一项评估ICP-248在慢性淋巴细胞白血病/小淋巴细胞白血病（CLL/SLL）、套细胞淋巴瘤（MCL）、边缘区淋巴瘤（MZL）患者中的临床试验正在开展。重点信息小编已整理好，供您参考。 试验药物简介  研究药物为新的高效、选择性BCL-2抑制剂，通过与BCL-2特异性结合，激活促凋亡蛋白BAD/BAK寡聚，从而增加线粒体膜的通透性，并释放细胞色素c，激活caspase介导的凋亡通路，引起肿瘤细胞凋亡，发挥抗肿瘤作用。 试验设计  分为剂量探索阶段和剂量拓展阶段。 主要入选标准  年龄≥ 18 岁且≤80岁。 根据2016年世界卫生组织（WHO）淋巴造血系统肿瘤分类标准或符合国际慢性淋巴细胞白血病研讨会（iwCLL）标准，经组织病理学和/或流式细胞学确诊为以下一种疾病：CLL/SLL、MCL、MZL 1）G/H队列：BTKi非难治其他BTKi治疗因不能耐受停药，但非治疗失败的患者；BTKi治疗后非治疗失败， 如治疗后获得CR/PR，PD发生于停药6个月后；或治疗不满6个月，评估为SD；没有暴露过任何BTKi的患者 2) I队列: 需要经 BTKi治疗的 CLL/SLL患者：既往使用过CD20（CLL/SLL患者除外）；ANC≥1.0×109/L,PLT≥50×109/L; 血红蛋白>8.0 g/dL; 肌酐清除率≥ 40 mL/min;左室射血分数（LVEF）≥50%；血清总胆红素≤1.5 ×ULN, AST和ALT ≤3× ULN ; APTT ≤1.5 ×ULN, INR ≤1.5 x ULN；CLL/SLL受试者需有治疗的指征。 3）J队列：ICP248联合奥布替尼，需要不论 BTKi 暴露史的 CLL/SLL患者不再限制； 4）K队列：ICP248联合奥布替尼、利妥昔单抗，既往未接受过系统性治疗的初治MCL患者；  主要排除标准  入组研究前2年内存在既往恶性肿瘤（研究疾病除外），但已经治愈的基底细胞或鳞状细胞皮肤癌、浅表性膀胱癌、宫颈或乳腺或胃肠道原位癌、肺原位腺癌伴或不伴微侵润、甲状腺乳头状癌或局部Gleason评分 ≤6分的前列腺癌除外。 已知淋巴瘤/白血病累及中枢神经系统。 存在研究者认为可能会导致接受研究药物有风险或者使安全性或有效性结果难以解释的基础医学疾病。 既往接受过自体干细胞移植（除非移植后 ≥3个月） 或既往嵌合细胞治疗（除非细胞输注后 ≥3个月）。 在首次使用试验药物前接受过BCL-2抑制剂治疗。 接受过异体干细胞移植的患者。 在首次使用试验药物前28天内，接受过抗肿瘤治疗（例如化疗、放疗、免疫治疗、生物治疗、激素治疗、临床研究中抗肿瘤治疗等） 末次使用强效CYP3A、CYP2C8抑制剂或诱导剂（西药、中药、膳食补充剂）距离首次试验用药时间不足5个半衰期，或者计划参与本研究期间同时服用强效CYP3A、CYP2C8抑制作用或诱导作用的药物、膳食补充剂或食物（如葡萄柚或葡萄柚汁等）。 有活动性感染 乙肝、丙肝、HIV 有严重的心血管疾病史的患者 咨询和参组方式  淋巴瘤之家已协助对接该研究团队，扫码咨询临床试验小伙伴即可。 1 慢淋/小淋（CLL/SLL），备注“BCL-2” 2 套细胞淋巴瘤（MCL），备注“BCL-2” 3 边缘区淋巴瘤（MZL），备注“BCL-2” END 编辑：关关  | 排版：悠然  | 审核：关关 声明：本文中涉及的信息仅供淋巴瘤病友及家属交流参考，不作为用药推荐，具体诊疗方案请遵从专业医生的意见或指导。 关于淋巴瘤之家 淋巴瘤之家是中国唯一覆盖全国范围的淋巴瘤患者组织，是国际抗癌联盟、国际淋巴瘤联盟、国际患者联盟、国际慢淋倡导网络的成员，以及国际华氏巨球蛋白血症基金会的合作伙伴。 2011 年由霍奇金淋巴瘤康复病友洪飞创立，其多数工作人员为有过淋巴瘤经历的患者和家属，以“让患者少走弯路，让治愈加速到来”为使命。 在众多淋巴瘤权威医学专家，患者、学者、创新药研发企业们的支持下，淋巴瘤之家成为了被患者认可、提供暖心守护与贴心陪伴的家园。2026年，注册用户已经超过 16万人，每年新增用户超过 2 万人。 关注一下  抗瘤少走弯路

Sanofi’s Cenrifki (tolebrutinib) approved in the EU as the first disability-targeting medicine for secondary progressive multiple sclerosis without relapses Cenrifki represents a significant advancement for people living with SPMS by targeting disability progression Approval based on the HERCULES phase 3 study in nrSPMS with supporting data from the GEMINI 1 and 2 phase 3 studies in RMS Paris, June 23, 2026 . The European Commission has approved Cenrifki (tolebrutinib) for the treatment of secondary progressive multiple sclerosis (SPMS) without relapses in the last two years. This follows the positive opinion by the European Medicines Agency's Committee for Medicinal Products for Human Use. The approval is based on results from the HERCULES phase 3 study (clinical study identifier: NCT04411641 ) in non-relapsing SPMS (nrSPMS), with supporting data from the GEMINI 1 (clinical study identifier: NCT04410978 ) and GEMINI 2 (clinical study identifier: NCT04410991 ) phase 3 studies in relapsing multiple sclerosis (RMS). The HERCULES study demonstrated that Cenrifki significantly delayed the onset of disability progression in nrSPMS. The safety pro Cenrifki has been consistent across the clinical program. The most common adverse events were COVID-19 and upper respiratory tract infections. Significant liver enzyme elevations were also observed. Drug-induced liver injury (DILI) is an identified safety risk of Cenrifki. Strict adherence to liver monitoring requirements, and prompt management of liver enzyme elevations, are important to mitigate DILI risk. Sanofi will make Cenrifki commercially available in Germany this year in close collaboration between local medical teams, treating MS specialists and their patients, all supported by the required Risk Management Program and robust Patient Support Program. This reflects Sanofi’s commitment to a careful approach to introducing this innovative, first-in-class medicine for people living with SPMS without relapses. About secondary progressive multiple sclerosis SPMS is a debilitating stage of MS where patients experience continuous accumulation of disability, including fatigue, cognitive impairment, mobility difficulties, and loss of independence – often without available treatment options. Across major European economies, the yearly cost of MS-related disability surpasses the average annual income per person. As disability accumulates, many are forced to reduce working hours or leave the workforce entirely — while up to 82% of those living with severe MS rely on informal caregiving, extending the strain far beyond the individual. Addressing disability progression remains one of the most significant unmet needs in MS care. About HERCULES HERCULES (clinical study identifier: NCT04411641 ) was a double-blind, randomized phase 3 clinical study evaluating the efficacy and safety of tolebrutinib in patients with nrSPMS. At baseline, nrSPMS was defined as having a SPMS diagnosis with an expanded disability status scale (EDSS) between 3.0 and 6.5, no clinical relapses for the previous 24 months and documented evidence of disability accumulation in the previous 12 months. Participants were randomized (2:1) to receive either an oral daily dose of tolebrutinib or matching placebo for up to approximately 48 months. The primary endpoint was six-month confirmed disability progression (CDP) defined as the increase of ≥1.0 point from the baseline EDSS score when the baseline score is ≤5.0, or the increase of ≥0.5 point when the baseline EDSS score was >5.0. Secondary endpoints included time to onset of three-month CDP as assessed by EDSS score, total number of new or enlarging T2 hyperintense lesions as detected by MRI, time to onset of confirmed disability improvement, 3-month change in 9-hole peg test and timed 25-foot walk test, as well as the safety and tolerability of tolebrutinib. About GEMINI 1 and 2 GEMINI 1 (clinical study identifier: NCT04410978 ) and GEMINI 2 (clinical study identifier: NCT04410991 ) were double-blind, randomized phase 3 clinical studies evaluating the efficacy and safety of tolebrutinib compared to teriflunomide, an oral disease-modifying medicine, in patients with RMS. Participants were randomized in both studies (1:1) to receive either tolebrutinib and placebo daily or 14 mg teriflunomide and placebo. The primary endpoint for both studies was the annualized relapse rate for up to approximately 36 months defined as the number of confirmed adjudicated protocol defined relapses. Secondary endpoints included time to onset of confirmed disease worsening, confirmed over at least six months, defined as an increase of ≥1.5 points from the baseline EDSS score when the baseline score is 0, an increase of ≥1.0 point from the baseline EDSS score when the baseline score is 0.5 to ≤5.5 or an increase of ≥0.5 point from the baseline EDSS score when the baseline score was >5.5 in addition to the total number of new and/or enlarging T2 hyperintense lesions as detected by MRI from baseline through the end of study, the total number of Gd-enhancing T1 hyperintense lesions as detected by MRI from baseline through the end of study, and the safety and tolerability of tolebrutinib. About Cenrifki Cenrifki (tolebrutinib) is an oral, brain-penetrant Bruton's tyrosine kinase inhibitor specifically designed to target smoldering neuroinflammation, a key driver of disability progression in MS. This unique mechanism of action addresses the underlying biology of progressive MS by targeting the inflammatory processes that contribute to disability accumulation. Cenrifki is the first disease-targeting therapy designed to address the underlying process of MS disability accumulation approved in the EU for adults with SPMS without relapses in the last two years. Cenrifki is administered once daily with a meal, and treatment should be initiated and supervised by a physician experienced in the management of multiple sclerosis. Cenrifki is also approved in Australia for the treatment of nrSPMS and to slow disability accumulation in the absence of relapse activity with SPMS and in the United Arab Emirates for the treatment of SPMS without relapses in the last two years. Cenrifki represents Sanofi's commitment to developing innovative treatments that address the underlying causes of neurological diseases and potentially transform the treatment landscape. Standing at the intersection of neurology and immunoscience, Sanofi is focused on improving the lives of those living with serious neuro-inflammatory and neuro-degenerative conditions including MS, chronic inflammatory demyelinating polyneuropathy, Alzheimer’s disease, Parkinson’s disease, age-related macular degeneration, and other neurological diseases. The neurology pipeline currently has several projects in phase 3 studies across various diseases. About Sanofi Sanofi is an R&D driven, AI-powered biopharma company committed to improving people’s lives and delivering compelling growth. We apply our deep understanding of the immune system to invent medicines and vaccines that treat and protect millions of people around the world, with an innovative pipeline that could benefit millions more. Our team is guided by one purpose: we chase the miracles of science to improve people’s lives; this inspires us to drive progress and deliver positive impact for our people and the communities we serve, by addressing the most urgent healthcare, environmental, and societal challenges of our time. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY Media Relations Sandrine Guendoul | +33 6 25 09 14 25 | sandrine.guendoul@sanofi.com Evan Berland | +1 215 432 0234 | evan.berland@sanofi.com Léo Le Bourhis | +33 6 75 06 43 81 | leo.lebourhis@sanofi.com Victor Rouault | +1 617 356 4751 | victor.rouault@sanofi.com Timothy Gilbert | +1 516 521 2929 | timothy.gilbert@sanofi.com Léa Ubaldi | +33 6 30 19 66 46 | lea.ubaldi@sanofi.com Ekaterina Pesheva | +1 410 926 6780 | ekaterina.pesheva@sanofi.com Laura Romby | +33 6 74 16 74 29 | laura.romby@sanofi.com Investor Relations Thomas Kudsk Larsen |+ 44 7545 513 693 | thomas.larsen@sanofi.com Alizé Kaisserian | + 33 6 47 04 12 11 | alize.kaisserian@sanofi.com Keita Browne | + 1 781 249 1766 | keita.browne@sanofi.com Nathalie Pham | + 33 7 85 93 30 17 | nathalie.pham@sanofi.com Nina Goworek | +1 908 569 7086 | nina.goworek@sanofi.com Thibaud Châtelet | + 33 6 80 80 89 90 | thibaud.chatelet@sanofi.com Yun Li | +33 6 84 00 90 72 | yun.li3@sanofi.com Sanofi Forward-Looking Statements This press release contains forward-looking statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995, as amended. 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The risks and uncertainties also include the uncertainties discussed or identified in the public filings with the SEC and the French Markets Authority (AMF) made by Sanofi, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s annual report on Form 20-F for the year ended December 31, 2025 or contained in our periodic reports on Form 6-K. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. In light of these risks, uncertainties and assumptions, you should not place undue reliance on any forward-looking statements contained herein. All trademarks mentioned in this press release are the property of the Sanofi group. Attachment Press_Release