Teriflunomide

2026年5月，美国FDA批准奥瑞珠单抗（ocrelizumab，商品名Ocrevus）用于治疗儿童复发缓解型多发性硬化（RRMS）。这一批准基于OPERETTA II期临床研究，为儿童MS患者带来了更有效的治疗选择。一、儿童MS：未被满足的治疗需求 多发性硬化是一种免疫介导的中枢神经系统慢性脱髓鞘疾病，好发于20-40岁青壮年，但儿童及青少年病例约占全部患者的5%-10%，且全球发病检出率逐年升高。 与成人相比，儿童MS有三大特点：复发更频繁，年复发率可达成人的1.5-2倍；诊断更困难，10岁以下患儿表现常不典型，儿童MS多为复发病程，而急性播散性脑脊髓炎（ADEM）多为单次单相病程，这是二者核心鉴别要点；治疗更局限，此前FDA正式获批用于儿童RRMS的口服DMT药物仅特立氟胺、芬戈莫德、西尼莫德，干扰素β多为临床超说明书应用，整体儿童治疗选择十分有限。 更关键的是，儿童期大脑仍在发育，反复炎症发作可能损伤正在形成的神经环路，对认知功能和运动发育造成不可逆影响。尽早有效控制疾病活动，对患儿长期预后至关重要。二、奥瑞珠单抗：CD20靶向治疗新选择 奥瑞珠单抗是全球首个全人源靶向CD20阳性B细胞的单克隆抗体，通过选择性清除致病性B淋巴细胞，阻断其中枢神经系统的免疫攻击。 自2017年获批成人MS适应症以来，奥瑞珠单抗已成为成人RRMS和原发进展型MS的标准治疗之一。多项III期研究证实，其能显著降低年复发率、减少MRI病灶活动、延缓残疾进展。每6个月一次静脉输注的给药方式，也大幅提高了患者依从性。 此次儿童适应症获批基于OPERETTA II期研究。这是一项国际多中心、随机、双盲、阳性药物对照试验，纳入10–17岁、疾病活动度较高的复发缓解型多发性硬化（RRMS）患儿，以芬戈莫德（既往FDA获批的经典儿童RRMS口服DMT药物）为阳性对照，头对头比较二者疗效与安全性。三、核心数据：多项指标显著优于芬戈莫德 OPERETTA II期研究主要终点达成非劣效：在10–17岁RRMS患儿中，奥瑞珠单抗降低年复发率（ARR）的效果不劣于芬戈莫德。在预设的关键MRI次要终点上，奥瑞珠单抗展现出显著优效性；在影像学炎症控制层面，显著优于传统一线口服DMT药物： 年化新发/扩大T2病灶相对减少48%——12个月研究周期内，奥瑞珠单抗组新发或扩大的T2病灶数量相比芬戈莫德组减少近一半。T2病灶负荷是反映疾病炎症活动度的敏感指标，病灶减少意味着中枢神经系统炎症得到更有效控制。对于发育中的儿童大脑，减少炎症发作具有特殊的神经保护意义。 年化急性钆增强病灶相对减少87%——这是最令人关注的数据。钆增强病灶代表血脑屏障破坏处的急性活动性炎症，是当前疾病活动的最直接标志。接近九成的降幅表明，奥瑞珠单抗对急性活动性炎症的抑制作用显著强于芬戈莫德。 该强效抗炎优势在高疾病活动度患儿中获益更突出。对于复发频繁、MRI病灶负荷重的高度活动型儿童MS患者，这种强劲的抗炎作用可能帮助他们实现更深度的疾病缓解，减少残疾累积。 安全性与成人整体相似——奥瑞珠单抗在儿童中的安全性谱与成人患者整体相似，未出现非预期新发严重不良事件。常见不良反应包括轻度输注相关反应、上呼吸道感染等，总体耐受性良好。但儿童处于免疫发育阶段，体液免疫抑制、感染风险仍需长期重点监测。四、临床意义：改变儿童MS治疗格局 奥瑞珠单抗儿童RRMS适应症的获批，将从三方面改变儿童MS治疗现状： 高度活动患儿有了新武器——对于传统DMT药物疗效不佳、疾病高度活动的患儿，奥瑞珠单抗提供了更强效的治疗选择。这部分患儿此前往往面临治疗手段有限的困境，新药物的加入让医生有了更多应对方案。 给药便利性大幅提升——每6个月一次静脉输注的长效给药模式，相较于儿童传统每日口服DMT方案，可显著降低长期服药频次、提升治疗依从性，也减少了频繁就医对学业和生活的干扰。 推动治疗理念升级——近年来成人MS领域已普及早期高强度治疗（escalate early）理念，儿童MS既往多采用保守阶梯治疗。奥瑞珠单抗在儿童中的获批，为高活动度患儿早期强效干预提供了药物基础，并非完全否定阶梯方案，而是为医生提供了更灵活的分层治疗选择。五、理性看待：仍需关注的问题 在欢迎新治疗选择的同时，也需要理性看待几个问题： 长期数据仍待积累——OPERETTA仅为12个月短期II期研究，缺乏2年以上长期复发、残疾累积、儿童生长发育及免疫系统成熟的随访数据，远期安全性与获益仍需大样本真实世界研究持续验证。 感染风险需警惕——B细胞清除治疗会一定程度影响体液免疫功能，增加感染风险。治疗前需筛查乙肝、结核等潜伏感染，治疗期间注意感染防控，定期监测免疫球蛋白水平。奥瑞珠单抗儿童临床试验暂无PML病例报道，儿童整体PML风险显著低于成人；但长期持续B细胞清除治疗仍需定期监测JC病毒抗体，做好远期风险警戒。 可及性仍是挑战——作为生物制剂，奥瑞珠单抗治疗成本相对较高。如何让有需要的患儿用得上、用得起，是需要共同面对的问题。六、给患儿家庭的几点建议 如果您的孩子正在考虑奥瑞珠单抗治疗，以下几点供参考： 充分沟通，理性决策——与医生详细沟通治疗的获益与风险，结合孩子的具体病情、年龄、身体状况，共同做出最适合的治疗选择。 做好感染预防——治疗前按要求完成各项筛查；治疗期间注意个人卫生，避免去人员密集场所，在医生指导下接种必要的灭活疫苗。 坚持定期随访——按医嘱定期复查血常规、免疫球蛋白、MRI等，以及时评估疗效、发现潜在不良反应。同时关注孩子的生长发育情况。 关注心理健康——慢性病对孩子的心理影响不容忽视。鼓励孩子保持积极心态，必要时寻求心理支持。 综合管理是关键——药物治疗只是MS管理的一部分。均衡营养、规律作息、适度运动、康复训练，多管齐下才能帮助孩子获得最佳预后。结语 奥瑞珠单抗儿童RRMS适应症的获批，是儿童MS治疗领域的重要进展。随着更多研究的开展和真实世界数据的积累，我们期待未来能有更精准的治疗分层、更安全的治疗方案，以及更多创新疗法的涌现，为患儿带来长期获益。 本文仅供医学科普，不构成诊疗建议。具体治疗方案请咨询专业医生。

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. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions regarding the marketing and other potential of the product; regarding potential future events and revenues from the product. Words such as “expect,” “anticipate,” “believe,” “intend,” “estimate,” “plan,” “can,” “contemplate,” “could,” “is designed to,” “may,” “might,” “potential,” “objective,” "attempt," “target,” “project,” "strategy," "strive," "desire," “predict,” “forecast,” “ambition,” “guideline,” "seek," “should,” “will,” "goal," or the negative of these and similar expressions are intended to identify forward-looking statements. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks, uncertainties and assumptions include among other things, unexpected regulatory actions or delays, or government regulation generally, that could affect the availability or commercial potential of the product, the fact that product may not be commercially successful; authorities’ decisions regarding whether and when to approve a product candidate; political pressure in the United States to mandate lower drug prices including “most favored nation” pricing for State Medicaid programs; the uncertainties inherent in research and development, including future clinical data and analysis of existing clinical data relating to the product, including post marketing, unexpected safety, quality or manufacturing issues; competition in general; risks associated with intellectual property and any related pending or future litigation and the ultimate outcome of such litigation, and volatile economic and market conditions, and the impact that global crises may have on us, our customers, suppliers, vendors, and other business partners, and the financial condition of any one of them, as well as on our employees and on the global economy as a whole. 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