SIPO1-AD: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Siponimod in Patients With Mild Alzheimer&Amp;#39;s Disease Dementia

Collaboration with multiple sclerosis (MS) specialty colleagues led us to formulate the central hypothesis that Siponimod could lower the rate of brain atrophy in Alzheimer's disease (AD) subjects. To test our central hypothesis, we will carry out an 18-month Phase II, double-blind, randomized, twoarmed, placebo controlled, proof-of-concept clinical study in early AD subjects (i.e. mild AD) who will be receiving an escalating dose of Siponimod or placebo in the ratio 2:1 for 12 months, followed by a 6-month washout period. The primary outcome measures are safety and tolerability of Siponimod in mild AD subjects. The secondary outcome measures are the rates of brain atrophy derived from volumetric MRI (vMRI) as a proxy for neurodegeneration conducted at baseline, 6, 12, and 18 months. The tertiary outcome measures are the changes in cognition and the levels of AD-associated (e.g., Aβ and tau) and inflammatory biomarkers in CSF after Siponimod exposure. In an exploratory effort, we will also measure plasma inflammatory markers during the entire duration of the study to investigate whether one or more of these markers can be used as dynamic surrogate markers of treatment response. Using our unique experience with the repurposing of immunomodulatory drugs for AD (and NCT #04032626), in the present project we are using elements of clinical trial design that we believe were successful and made some adjustments to fit the pharmacologic and toxic properties of Siponimod.

开始日期2025-07-01

申办/合作机构

St. Joseph's Medical Center, Inc.

[+5]

CTR20232992

/ CompletedN/A

西尼莫德片的人体生物等效性研究

研究空腹/餐后状态下单次口服受试制剂西尼莫德片与参比制剂西尼莫德片（万立能®）在健康成年受试者体内的药代动力学，评价空腹/餐后状态下口服两种制剂的生物等效性和安全性。

开始日期2023-09-23

申办/合作机构

齐鲁制药有限公司

CTR20230278

/ Completed临床4期

一项在中国复发型多发性硬化患者中评价BAF312的有效性和安全性的回顾性、多中心真实世界研究。

1.在中国真实世界人群中，基于年复发率描述BAF312在复发型多发性硬化(RMS)患者中的有效性。 2.描述开始BAF312治疗后12个月时保持无复发的患者比例。 3.在中国真实世界人群中描述BAF312在RMS患者中的安全性特征。 4.描述开始BAF312治疗后12个月时无MRI活动性的患者比例。

开始日期2023-04-23

申办/合作机构

Novartis Farmacéutica SA

[+3]

100 项与西尼莫德相关的临床结果

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100 项与西尼莫德相关的转化医学

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100 项与西尼莫德相关的专利（医药）

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354

项与西尼莫德相关的文献（医药）

2025-08-01·Neurology and Therapy

Comparative Effectiveness of Fumarates Versus Sphingosine-1-Phosphate Receptor Modulators in Black Patients with Multiple Sclerosis

Article

作者: Shankar, Sai L ; Romero, Rebecca S ; Walker, Aljoeson ; Bian, Boyang ; Guo, Chu-Yueh ; Woodson, Sophia ; Lee, Jong-Mi ; Fong, Kinyee ; Mendoza, Jason P ; Belviso, Nicholas ; Lewin, James B ; Klineova, Sylvia ; Gettings, Edward J

INTRODUCTION:

Multiple sclerosis (MS) is a heterogeneous disease that disproportionately impacts Black people with MS (PwMS), who experience more severe disease and higher relapse rates compared with non-Black populations. Despite widespread use of fumarates and sphingosine-1-phosphate (S1P) receptor modulators as oral disease-modifying therapies (DMTs) for relapsing MS, their comparative effectiveness in Black PwMS has not been studied. This study aims to help address this gap using real-world claims data.

METHODS:

This retrospective analysis using the Komodo Health Claims Database included Black PwMS. Patients were aged 18-64 years with ≥ 1 claim for MS diagnosis (International Classification of Diseases, Tenth Revision, Clinical Modification code G35) and ≥ 1 prescription claim for fumarates (dimethyl fumarate or diroximel fumarate) or an S1P receptor modulator (fingolimod, siponimod, ozanimod, or ponesimod) between January 2017 and April 2023. Outcomes included annualized relapse rate (ARR) and time to first relapse. Propensity score matching (2:1) and inverse probability weighting were used to balance baseline characteristics. Relapse events were identified using a claims-based algorithm.

RESULTS:

The analysis included 1664 Black PwMS (1231 and 433 in fumarate and S1P treatment arms, respectively). Post-index ARRs were comparable between groups (rate ratio [RR] 1.18, p = 0.423). Kaplan-Meier analyses showed similar relapse-free proportions at 24 months (72.6% and 74.7% in fumerate and S1P populations, respectively; p = 0.152). These findings were consistent in both the propensity score-matched and inverse probability weighted populations.

CONCLUSIONS:

This real-world, claims-based analysis demonstrates that fumarates and S1P receptor modulators have similar effectiveness in reducing relapses among Black PwMS, with > 72% of patients in both treatment groups remaining relapse-free at 24 months. Given the underrepresentation of Black patients in MS clinical trials, these results provide valuable real-world evidence to guide treatment decisions for this population.

2025-07-01·JOURNAL OF THE NEUROLOGICAL SCIENCES

Safety assessment of switching from fingolimod to siponimod: An Italian multicenter prospective study

Article

作者: Inglese, Matilde ; Signori, Alessio ; Tomasso, Ilaria ; Cellerino, Maria ; Fantozzi, Roberta ; Marinelli, Fabiana ; Scarano, Valentina ; Abbadessa, Gianmarco ; Lavorgna, Luigi ; Ferrazzano, Gina ; Pasquali, Livia ; Buttari, Fabio ; Sormani, Maria Pia ; Schiavetti, Irene ; Bile, Floriana ; Miele, Giuseppina ; Maida, Elisabetta ; Cavalla, Paola ; Bulgari, Alessandro ; Clerico, Marinella ; De Luca, Giovanna ; Vercellino, Marco ; Bollo, Luca ; Landi, Doriana ; Zanghì, Aurora ; Iaffaldano, Pietro ; Clerici, Valentina Torri ; Buscarinu, Maria Chiara ; Trotta, Maria ; Smolik, Krzysztof ; Bonavita, Simona ; D'Amico, Emanuele

INTRODUCTION:

Safety concerns have been raised regarding fingolimod to siponimod transition in people with Secondary Progressive Multiple Sclerosis (SPMS).

OBJECTIVE:

To explore factors associated with the choice of switching from fingolimod to siponimod and the safety of this sequencing.

METHODS:

We conducted a prospective observational study that included patients who had a confirmed diagnosis of SPMS at the time of study entry and had been treated with fingolimod for at least two years. Upon enrollment, patients either continued fingolimod (comparator group) or transitioned to siponimod (switch group) and were followed up for six months to assess disease activity and changes in laboratory parameters.

RESULTS:

Out of 95 SPMS subjects, 42 (44.2 %) switched to siponimod at study entry. The switch group was younger and had more prior treatments than the comparator group (p = 0.042 and p = 0.015, respectively). Five subjects experienced disease activity (three in the switch group, two in the comparator). Patients switching to siponimod experienced a greater increase in GPT (p = 0.015) and GOT levels (p = 0.041) at 6 months. Four adverse events were reported: melanoma and grade IV lymphopenia in the comparator group, and grade IV lymphopenia and dizziness in the switch group.

CONCLUSION:

During the 6-month observation period, switching from fingolimod to siponimod was safe in terms of disease reactivation and tolerability.

2025-06-01·NEUROREHABILITATION

What Is the Evidence on Immunomodulators and Immunosuppressants for Progressive Multiple Sclerosis? - A Cochrane Review Summary with Commentary.

Review

作者: Moretti, Antimo

BackgroundMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting the central nervous system and is a major cause of disability in adults, particularly in those affected by progressive MS. A variety of drugs with different effects, some carrying significant risks, are currently available, making evidence-based approach essential for clinicians treating MS patients.ObjectiveTo compare the efficacy and safety of immunomodulators and immunosuppressants for progressive multiple sclerosis (PMS).MethodsA systematic search was performed in CENTRAL, MEDLINE, Embase, and trials registers on 8 august 2022, including RCTs comparing immunomodulators and immunosuppressants versus placebo or another drug.ResultsThe network meta-analysis (NMA) included 23 RCTs (with 10,167 participants). Moderate certainty of evidence suggests that rituximab probably not reduce the risk of relapse at 2 years, while interferon beta-1b probably reduces the risk of relapses at 3 years (-18%) compared to placebo in PMS people. Regarding SAE, low-to-very-low certainty of evidence for no increased risk with disease-modifying therapies (DMTs) versus placebo is available, except for immunoglobulins that seem to have a 7-fold increased risk of serious adverse events (SAEs). Only low-to-very low certainty of evidence is available about disability progression and SAEs in PMS people treated with DMTs versus placebo. On the other side, the risk for treatment discontinuation due to AEs is increased with interferon beta-1a by 2.93-fold, and probably increased with interferon-beta-1b, glatiramer acetate, and fingolimod by 2.98-fold, 3.98-fold, and 2.29-fold, respectively. Also, rituximab, natalizumab, siponimod, and ocrelizumab probably do not increase the risk for treatment discontinuation due to AEs, while laquinimod may not increase the risk treatment discontinuation due to AEs.ConclusionsCompared with placebo, two-, and three-year treatment with rituximab or interferon beta-1b, respectively, probably slightly reduce relapses in PMS people. A slight increase of treatment discontinuation due to AEs has been reported for rituximab, interferon beta-1b, interferon beta-1a, immunoglobulins, glatiramer acetate, natalizumab, fingolimod, siponimod, and ocrelizumab. No reliable evidence is available for disability progression and SAEs with available DMTs compared to placebo.

项与西尼莫德相关的新闻（医药）

2025-06-18

·米内网

科伦药业厉害了！拿下35个重磅品种，26款1类新药、74个新品出击，198个过评品种霸屏

精彩内容近段时间，科伦药业产品管线进展频频：1类新药注射用SKB315新适应症获批临床、注射用头孢唑林钠/氯化钠注射液国内第2家获批等。近年来，科伦药业坚持“三发驱动，创新增长”的发展战略，2024年研发投入21.71亿元（+11.2%），目前有42款新药（26款1类新药）处于申报临床及以上阶段；仿制药方面，累计有198个品种过评（50余个首家/独家），74个新品瞄准160亿市场。拿下35个品种！198个过评品种霸屏近日，科伦药业2款3类仿制药获批生产并视同过评，为注射用头孢唑林钠/氯化钠注射液、注射用青霉素钠，均属于全身用抗感染药物。其中，注射用头孢唑林钠/氯化钠注射液国内第2家获批，同时也是公司粉液双室袋平台第11个获批的产品。今年以来，科伦药业（含子公司及联营公司，下同）产品管线持续推进。在新注册分类品种审评方面，科伦药业有35个品种获批生产并视同过评，领跑国内其他药企。2025年以来科伦药业获批上市的仿制药来源：米内网中国申报进度（MED）数据库35个品种中，有多个品种为国内首批上市，其中芦曲泊帕片、注射用亚胺培南西司他丁钠/氯化钠注射液、注射用比阿培南/氯化钠注射液等为国内首仿+首家过评，阿帕他胺片、枸橼酸钠血滤置换液、注射用头孢他啶/氯化钠注射液等为国产第2家获批，复方氨基酸注射液(18AA-Ⅸ)、他克莫司缓释胶囊、昂丹司琼口溶膜、复方电解质醋酸钠注射液等为国产第3家获批等。截至目前，科伦药业已有198个品种通过/视同通过一致性评价，在过评品种数TOP10集团中排位第二。其中，50余个品种为国内首家过评，包括芦曲泊帕片、氢溴酸替格列汀片、琥珀酸曲格列汀片、泊沙康唑口服混悬液、注射用比阿培南/氯化钠注射液、注射用亚胺培南西司他丁钠/氯化钠注射液等18个独家过评品种。在国家开展的九批十轮化药集采中，科伦药业分别有1个、5个、4个、4个、11个、11个、7个、4个、12个品种成功中选，合计59个品种。集采常态化推进背景下，科伦药业恰逢产品线密集收获期，并积极参与集采，目前已成为集采头部供应商之一。在第十一批集采中，预计科伦药业将仍旧为“主力军”，目前已有近40个品种达到入围门槛，注射剂占“半壁江山”。其中，有10余个为2025年后新获批品种，包括罗沙司他胶囊、注射用头孢他啶阿维巴坦钠(4:1)等临床畅销品种。26款1类新药出击，猛攻2300亿市场今年以来，科伦药业国内新药研发进展不断：生物类似药西妥昔单抗注射液获批上市，为国产首家；PD-L1单抗塔戈利单抗注射液、TROP2 ADC注射用芦康沙妥珠单抗获批新适应症；1类新药注射用SKB445、SKB107注射液，以及2.2类改良型新药KLA480注射液、注射用KLA578-1、KLA514-2片、A140注射液等均首次获批临床。国际化方面，新型ADC药物SKB518在美获批临床，用于治疗晚期实体瘤，该药已在国内开展II期临床试验；以不超过9.7亿美元的首付款和里程碑付款，将TSLP单抗SKB378/HBM93781在全球范围内（不包括大中华区以及部分东南亚及西亚国家）的研发、生产和商业化的独家授权给Windward Bio等。近年来，科伦药业坚持“三发驱动，创新增长”的发展战略，不断加大研发投入支持创新发展。2023年公司研发投入19.5亿元，同比增长7.59%；2024年进一步增长至21.71亿元，同比增长11.2%。近年来科伦药业研发投入情况（单位：亿元）来源：公司公告，米内网整理目前科伦药业有42款新药在国内处于申报临床及以上阶段，涉及26款1类新药、15款2类改良型新药、1款生物类似药，聚焦肿瘤、精神神经、心血管、肝病、呼吸等疾病领域，其中抗肿瘤药独占“半壁江山”。米内网数据显示，2024年中国三大终端六大市场抗肿瘤和免疫调节剂（化学药+生物药）销售额超过2300亿元。科伦药业国内在研新药来源：米内网综合数据库42款新药中，1类新药注射用博度曲妥珠单抗、制剂改良型新药布瑞哌唑口溶膜已申报NDA，上市可期。博度曲妥珠单抗为靶向HER2的ADC药物，全球已获批上市的同靶点同类型药物中，罗氏的恩美曲妥珠单抗、第一药品/阿斯利康的德曲妥珠单抗2024年全球销售额分别达19.98亿瑞士法郎、5.45亿美元。口溶膜制剂方面，昂丹司琼口溶膜已顺利获批，布瑞哌唑口溶膜、枸橼酸西地那非口溶膜2款产品报产在审，盐酸达泊西汀口溶膜、盐酸鲁拉西酮口溶膜等获批临床，提升了公司复杂制剂领域产线价值。在研1类新药中，ADC药物是科伦药业重点布局的药物形式之一，目前已有芦康沙妥珠单抗（TROP2 ADC）1款新药获批上市，此外还有9款ADC药物处于获批临床及以上阶段，其中新型双抗ADC药物SKB571，以及SKB518、MK-6204、SKB445等具有潜在FIC靶点的新型ADC药物等均处于I期临床。目前全球已有10多款ADC药物获批上市，2024年全球销售额合计约130亿美元。74个新品瞄准160亿市场！29个品种抢首仿仿制药申报方面，目前科伦药业还有74个新注册分类品种在审（不含已有批文、主动撤回品种），形成了梯度丰富的研发管线，主要集中在血液和造血系统药物（16个）、神经系统药物（15个）、全身用抗感染药物（8个）、消化系统及代谢药（7个）等。74个品种2024年在中国三大终端六大市场的销售额合计超过160亿元。其中，低钙腹膜透析液(乳酸盐-G1.5%)、艾拉莫德片均超过10亿元，低钙腹膜透析液(乳酸盐-G2.5%)、丙戊酸钠缓释片(Ⅰ)均超过9亿元，双氯芬酸二乙胺乳胶剂、磷酸芦可替尼片均超过8亿元。29个品种暂无首仿（含剂型首仿）获批上市，包括注射用头孢噻肟钠/氯化钠注射液、注射用盐酸头孢替安/氯化钠注射液、雌二醇地屈孕酮片、佩玛贝特片、苯磺酸氨氯地平口服溶液、甲磺酸沙非胺片、苹果酸奈诺沙星氯化钠注射液、注射用头孢唑肟钠/氯化钠注射液、右美沙芬安非他酮缓释片、注射用阿立哌唑、枸橼酸西地那非口溶膜、布瑞哌唑片、罗替高汀贴片、奈妥匹坦帕洛诺司琼胶囊、西尼莫德片、奥贝胆酸片等。科伦药业新分类申报在审且暂无首仿获批的品种来源：米内网中国申报进度（MED）数据库此外，注射用头孢哌酮钠舒巴坦钠氯化钠注射液、伊布替尼片、双氯芬酸钠贴片、瑞舒伐他汀依折麦布片(Ⅰ)、屈螺酮炔雌醇片、磷酸芦可替尼片、结构脂肪乳注射液(C6-24)、腹膜透析液(碳酸氢盐-G4.25%)、复方聚乙二醇电解质散(Ⅱ)、恩他卡朋双多巴片(Ⅱ)、布立西坦片、吡仑帕奈口服混悬液、10%脂肪乳(OO)/5.5%氨基酸(15)/葡萄糖(20%)注射液等品种获批国产企业数均只有1家。资料来源：米内网数据库、公司公告等注：米内网《中国三大终端六大市场药品竞争格局》，统计范围是：城市公立医院和县级公立医院、城市社区中心和乡镇卫生院、城市实体药店和网上药店，不含民营医院、私人诊所、村卫生室，不含县乡村药店；上述销售额以产品在终端的平均零售价计算。数据统计截至6月16日，如有疏漏，欢迎指正！免责声明：本文仅作医药信息传播分享，并不构成投资或决策建议。本文为原创稿件，转载文章或引用数据请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092【分享、点赞、在看】点一点不失联哦

一致性评价上市批准生物类似药

2025-06-09

·医药观澜

为数百万患者带来曙光：BTK抑制剂等新兴疗法涌现，多发性硬化治疗正迎来新突破

编者按：多发性硬化（MS）是一种致残性自身免疫性中枢神经系统疾病。过去十多年间，多款新兴疗法获监管机构批准治疗MS，极大改善了患者的生存状况。作为医药和生命科学产业创新的赋能者，药明康德很高兴能为来自合作伙伴的多款MS新药提供赋能支持。但这一领域仍然存在未被满足的临床需求，新药研发面临诸多挑战。当前产业界正在不断寻求新型疗法，致力于为患者带来更安全、有效、便利的治疗选择。药明康德也将持续以一体化、端到端的CRDMO模式为全球合作伙伴提供从研究、开发到生产的全链条服务，助力加速创新疗法的问世，造福病患。今年上半年，多发性硬化（multiple sclerosis，MS）新药研发领域迎来了多项进展。3月，赛诺菲（Sanofi）宣布其BTK抑制剂tolebrutinib的上市申请已获得美国FDA授予优先审评资格，以治疗非复发性继发进展型多发性硬化症（nrSPMS），并延缓成人患者独立于复发活动的残疾进展。若获得批准，tolebrutinib有望成为首款既能治疗nrSPMS，又能减缓残疾累积而不受复发活动影响的脑穿透性BTK抑制剂。行业媒体也将这款疗法列入“2025年有望上市的10款潜在重磅疗法”。 4月，Immunic公司公布了其潜在first-in-class疗法——核受体相关1（Nurr1）激活剂vidofludimus calcium（IMU-838）在进展型多发性硬化症（PMS）患者中开展的2期CALLIPER试验的积极数据。与安慰剂相比，IMU-838将基于扩展残疾状态量表变化的24周确认残疾恶化事件的相对风险降低了20%。5月，罗氏（Roche）与旗下基因泰克（Genentech）也公布其BTK抑制剂fenebrutinib在复发型多发性硬化（RMS）患者中96周的最新研究数据。分析显示，患者在使用该药治疗近两年后的复发率低，脑部无活动性病灶，且功能障碍无进展。此外在细胞疗法领域也有一些进展，例如百时美施贵宝2月公布了其在研CD19靶向CAR-T细胞疗法的最新临床研究数据，该产品在复发缓解型多发性硬化（RRMS）患者中显示出良好的初始安全性。图片来源：123RF新一代疗法涌现，它们如何改变多发性硬化治疗作为一种复杂的神经退行性疾病，MS因较高复发率和高致残率给患者，尤其是青壮年，带来了严重的疾病负担。根据多发性硬化国际联合会（MSIF）2025年4月发布的数据，目前全球超过280万人罹患多发性硬化。过去十年间，有近10款新药获FDA批准治疗MS。这其中主要包括两类新机制药物，即靶向CD20阳性B细胞的单抗药物和S1P受体调节剂。抗CD20单抗如ofatumumab、ocrelizumab等，通过与B细胞表面的CD20结合，达到从血液循环中清除B细胞的效果。而这些细胞在MS患者中对激发自身免疫反应有重要作用。另一类是以ozanimod、siponimod为代表的第二代S1P受体调节剂。S1P是调节淋巴细胞迁移出淋巴结的信号，S1P受体调节剂可降低迁移到中枢神经系统、攻击髓鞘的炎症性淋巴细胞的数量，减轻髓鞘的损伤。第二代S1P受体调节剂能够有选择性地与S1PR1和S1PR5受体亚型结合，在降低血液和淋巴循环中的淋巴细胞数目，减少中枢神经系统的炎症反应的同时，降低可能出现的副作用。尽管过去二十年MS治疗取得显著进展，但疾病的高度异质性和血脑屏障的存在，使得现有疗法在长期疾病控制和神经保护方面仍面临挑战。针对这些挑战，研究人员正在探索包括BTK抑制剂、抗体疗法、细胞疗法等在内的新机制创新疗法。公开资料显示，目前全球范围内有数十款新药在临床阶段探索治疗MS的潜力。其中少数几款产品进入3期临床阶段，包括多款脑穿透性BTK抑制剂，CD40L靶向单抗、神经保护转录因子Nurr1激活剂等等。此外，多款细胞疗法也在临床研究中展现出治疗MS的潜力。图片来源：123RFBTK抑制剂在MS的治疗潜力备受关注。现有的MS疗法主要针对外周炎症，它们在穿透中枢神经系统（CNS）的能力方面受到限制，因此开发能够跨越血脑屏障、靶向CNS内炎症的新疗法，成为MS新药开发的未来方向。目前，多款可穿越血脑屏障的BTK抑制剂正在临床阶段探索治疗MS的潜力。以tolebrutinib为例，该产品能够穿过血脑屏障，达到治疗性脑脊液浓度，使其能够调节中枢神经系统内的b淋巴细胞和疾病相关的小胶质细胞。这使得该产品能够靶向导致神经变性和残疾积累的炎症过程来治疗进展性MS。临床3期试验结果表明，与安慰剂相比，tolebrutinib可将非复发性继发进展型多发性硬化（nrSPMS）出现6个月确认残疾进展（CDP）的时间延缓31%。目前，全球还有多款具血脑屏障穿透性的BTK抑制剂正在临床阶段探索治疗MS的潜力。进展较快的产品如诺华（Novartis）在研的BTK抑制剂瑞米布替尼片（remibrutinib）、罗氏在研的BTK抑制剂fenebrutinib、诺诚健华BTK抑制剂奥布替尼等，均已进入治疗MS的3期临床研究阶段。CAR-T细胞疗法也是MS的研发方向之一。据报道，CAR-T疗法的理论优势在于B细胞耗竭更有效，能更好地清除自身反应性B细胞，从而可能诱导缓解，甚至有可能治愈疾病。针对MS，CAR-T疗法还具有直接穿过血脑屏障的优势。例如，Kyverna Therapeutics早前宣布，在两名进展性多发性硬化患者的脑脊液中观察到其所开发的CD19靶向CAR-T疗法KYV-101细胞的存在和扩增，并且在一名患者中观察到鞘内抗体水平的下降，这意味着CAR-T细胞可以靶向中枢神经系统中的CD19阳性B细胞。在穿透血脑屏障方面，研究人员还在探索其他的新方向，比如转铁蛋白受体（TfR）作为一种促进跨越血脑屏障运输的蛋白质，可以优化药物在大脑中的递送。目前针对该靶点的新药已经在其他神经系统疾病中取得积极进展。文献指出，同时靶向TfR和MS治疗靶点（如CD20）有望增强多发性硬化新药的CNS特异性递送。突破血脑屏障限制，加速神经系统疾病新药研发创新多发性硬化是神经系统疾病的类型之一，其治疗药物的研发一直面临诸多挑战。在这一领域，药明康德凭借“一体化、端到端”的CRDMO服务平台，持续为包括多发性硬化在内的神经系统疾病疗法开发提供全方位支持，助力全球合作伙伴加速新药问世。比如在近年来获FDA批准的MS创新疗法中，就有多款得到了药明康德的赋能。在中枢神经系统（CNS）领域，药物研发的成功率显著低于其他治疗领域。数据显示，CNS药物研发的成功率只有8%，不及其他治疗领域药物研发成功率的一半。其中主要原因之一为血脑屏障（Blood to Brain Barrier, BBB）的特性阻碍了药物入脑，影响其在脑中的暴露量。因此，血脑屏障通透性研究对CNS药物的开发具有重要的意义。公开信息显示，药明康德DMPK自2009年起开始进行CNS相关研究，拥有超过15年的临床前CNS药物研发经验，建立了针对CNS药物体外血脑屏障通透性评价的特色且准确性较高的“漏斗”模型。对于主要通过被动扩散入脑的CNS药物，“漏斗”模型的评估准确性为100%。通过完善的体外、体内测试平台，药明康德DMPK能够快速、准确、高效地对CNS药物进行全方位药代动力学相关评价，筛选出具有良好的脑通透性及稳定性的CNS候选药物。根据早前公开信息，该平台已完成包括常规小分子、治疗性蛋白、寡核苷酸等新分子实体类型项目百余项，成功助力全球客户多个CNS药物进入临床阶段。当前，随着BTK抑制剂、细胞疗法等创新疗法的涌现，多发性硬化治疗正迎来新契机。在持续丰富的研发管线推动下，这一曾被视为不可控的慢性疾病，正逐步向可管理可控的长期病况转变，为全球患者带来新的曙光。药明康德将继续以专业能力和规模赋能医药创新，与全球行业伙伴共同助力CNS治疗领域的新突破。参考资料：[1]Robert J. Fox, M.D. Amit Bar-Or, M.D., Anthony Traboulsee, M.D.Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis.April 8, 2025 N Engl J Med 2025;392:1883-1892 DOI: 10.1056/NEJMoa2415988[2]Tolebrutinib regulatory submission accepted for priority review in the US for patients with multiple sclerosis.Retrieved Mar 25,2025.From https://www.news.sanofi.us/2025-03-25-Tolebrutinib-regulatory-submission-accepted-for-priority-review-in-the-US-for-patients-with-multiple-sclerosis[3] Maria Pia Amato, Emilio Portaccio. Multiple sclerosis in 2024: evolving evidence and new hopes.THE LANCET Neurology, Volume 24, Issue 1p17-18 January 2025. DOI: 10.1016/S1474-4422(24)00483-6.[4] Conway SE, Galetta K. Therapeutic advances in multiple sclerosis: Novel therapies (immune checkpoint inhibitors, CAR-T, Anti-CD40L). Neurotherapeutics. 2025 Feb 27:e00558. doi: 10.1016/j.neurot.2025.e00558. Epub ahead of print. [5] 演讲回顾 | 药明康德科学论坛广州站：“漏斗”模型助力CNS药物渗透性评估 from https://mp.weixin.qq.com/s?__biz=MzkzMDE3OTkxNw==&mid=2247557971&idx=2&sn=c8c53b0e0fb3792fb29f4e2c0dfddaba&chksm=c325fffa6a1c6246ad71ca641497e6fa9b62fb4e73ff1adf927ac31c2d4fe5f0fa203fb53a24&poc_token=HBwYO2ijOdEaquwwLznsXEgS1lmDOSVpNVlOFN57[6]多发性硬化国际联合会（MSIF）官网https://www.msif.org/about-ms/what-is-ms/[7] Immunic Announces Vidofludimus Calcium Reduced Risk of Disability Worsening by 30% in Primary Progressive Multiple Sclerosis Patients from Phase 2 CALLIPER Trial.Retrieved Apr 30,2025.From https://ir.imux.com/2025-04-30-Immunic-Announces-Vidofludimus-Calcium-Reduced-Risk-of-Disability-Worsening-by-30-in-Primary-Progressive-Multiple-Sclerosis-Patients-from-Phase-2-CALLIPER-Trial版权说明：本文欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权或其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

细胞疗法优先审批临床2期申请上市免疫疗法

2025-05-01

·BioSpace

Immunic Talks Up Disability Gains as Phase II MS Therapy Fails on Primary Endpoint

iStock, dickcraft According to CEO Daniel Vitt, clinical and disability-related outcomes are more relevant than brain volume change for drug development in multiple sclerosis. Immunic’s oral multiple sclerosis drug failed to significantly slow the loss of brain volume in patients with a progressing form of the neurodegenerative disorder during a Phase II clinical trial. But according to CEO Daniel Vitt, it’s no big deal. “Nobody should care at all about whole brain volume change anymore,” Vitt said during an investor call on Wednesday to discuss the mid-stage data, noting that having brain volume as a primary endpoint of the Phase II study was just a “leftover” of a trial design that the biotech settled on “five years ago.” Instead, the field has now focused on using disability as an endpoint, Vitt said, noting that Immunic is taking the same approach, particularly for its Phase III trial. In that regard, Vitt asserted that Wednesday’s readout was a “very, very clear positive outcome.” Leerink analysts said the same thing, calling the CALLIPER results for the therapy, a Nurr1 activator called vidofludimus calcium, “positive” and “competitive” in an investor note on Wednesday. Vidofludimus calcium, according to the analysts, “demonstrated a competitive risk/benefit profile” in primary progressive multiple sclerosis (MS), as compared with Roche’s Ocrevus, and in non-active secondary progressive MS, relative to Novartis’ Mayzent and Sanofi’s tolebrutinib. Of course, this analysis comes with “usual cross-trial comparison caveats,” Leerink cautioned. “We believe the molecule has now demonstrated disease-modifying activity in a difficult-to-treat patient population with limited active lesions,” the analysts added. Immunic is running the Phase III ENSURE program to assess vidofludimus calcium, with data expected next year, Vitt said on the call. Leerink is likewise bullish about Immunic’s prospects here, with its analysts expecting a 50% probability of success. Data from CALLIPER showed that vidofludimus calcium improved the annualized rate of brain volume change by 5% relative to placebo—an effect that failed to reach statistical significance. Immunic, however, chose to focus on the clinical outcomes. The likelihood of having disability worsening events at 24 weeks, for instance, was 20% lower in the vidofludimus calcium group, as compared with placebo. This effect remained consistent or increased even further in various patient subgroups, including in those with primary progressive MS and in those without inflammatory lesions at baseline. As for safety, there were no new signals of concern with vidofludimus calcium. Severe side effects were “rare,” according to Immunic, and occurred at similar frequencies between the treatment arms: 8.1% in patients on vidofludimus calcium and 6.5% of placebo counterparts.

临床2期临床结果临床3期

100 项与西尼莫德相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	西尼莫德	L04AA42	DB12371

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
继发进展型多发性硬化	欧盟	Novartis Europharm Ltd.	2020-01-13
继发进展型多发性硬化	冰岛	Novartis Europharm Ltd.	2020-01-13
继发进展型多发性硬化	列支敦士登	Novartis Europharm Ltd.	2020-01-13
继发进展型多发性硬化	挪威	Novartis Europharm Ltd.	2020-01-13
多发性硬化症	美国	Novartis Pharmaceuticals Corp.	2019-03-26

未上市

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适应症	最高研发状态	国家/地区	公司	日期
复发性多发性硬化	临床3期	美国	Novartis Pharmaceuticals Corp.	2019-02-14
复发性多发性硬化	临床3期	波多黎各	Novartis Pharmaceuticals Corp.	2019-02-14
横纹肌肉瘤	临床3期	美国	Novartis Pharmaceuticals Corp.	2019-02-14
横纹肌肉瘤	临床3期	波多黎各	Novartis Pharmaceuticals Corp.	2019-02-14
阿尔茨海默症	临床2期	美国	Laboratory Corporation of America Holdings	2025-07-01
阿尔茨海默症	临床2期	美国	Novartis AG	2025-07-01
轻度认知障碍	临床2期	美国	Laboratory Corporation of America Holdings	2025-07-01
轻度认知障碍	临床2期	美国	Novartis AG	2025-07-01
脑出血	临床2期	美国	Novartis Pharmaceuticals Corp.	2017-12-24
出血性卒中	临床2期	美国	Novartis Pharmaceuticals Corp.	2017-12-24

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04925557 (CTgov)	临床2/3期	继发进展型多发性硬化	8	Ocrevus (Ocrevus)	觸遞糧範憲膚積觸廠襯(鹽蓋糧積衊遞蓋窪網醖) = 顧範淵鏇獵繭艱鬱鏇壓廠憲願願餘積構範夢襯 (壓繭壓醖廠夢蓋觸顧繭, 遞獵艱壓遞獵鹹獵製顧 ~ 選選鹽鬱繭鬱網壓築網) 更多	-	2025-05-13
				Mayzent (Mayzent)	觸遞糧範憲膚積觸廠襯(鹽蓋糧積衊遞蓋窪網醖) = 壓廠選憲網夢繭鏇繭壓廠憲願願餘積構範夢襯 (壓繭壓醖廠夢蓋觸顧繭, 鏇淵憲獵鏇積餘鏇窪繭 ~ 鏇繭簾構獵蓋鏇顧廠壓) 更多
NCT03623243 (EXCHANGE, Pubmed \| Mult Scler)	临床3期	复发性多发性硬化	185	Siponimod	壓糧夢獵鹽網願簾築網(壓範鹹選製齋餘獵醖醖) = 3.8% (n = 7) 觸鑰憲艱糧鹹獵繭繭範 (繭製選淵積鬱觸鹽鬱願 ) 更多	积极	2025-04-18
ECTRIMS2023	N/A	多发性硬化症	67	Siponimod	襯構夢淵範顧餘鹽鹹艱(遞餘鹽顧鑰衊選構鬱夢) = 願獵鹹顧觸襯製鬱壓遞範鏇顧範糧簾鑰簾窪醖 (鹹積鹽醖壓淵艱網鏇醖 )	-	2023-10-01
ACTRIMS2023	N/A	继发进展型多发性硬化二线	29	Siponimod	鏇網願構壓築積遞繭鏇(淵構築觸積鏇壓選簾構) = 4 patients discontinued treatment due to adverse events and one by personal decision. 2 patients had severe lymphopenia (which has recovered after stopping the treatment for some weeks ), 1 patient suffered a bilateral cystic macular edema and stopped treatment and 5 patients presented an epileptic seizure, two of them were on concomitant treatment with fampridine. Three of them have discontinued the treatment. No alterations in liver enzymes have been observed. No documented increase in frequent infections. 積膚遞選鹹觸鏇艱淵淵 (鹽構憲廠鬱蓋餘夢遞積 ) 更多	积极	2023-05-30
ECTRIMS2022	N/A	继发进展型多发性硬化 CYP2C9 genotype	-	Siponimod 2mg	壓醖糧鑰遞鬱壓齋齋糧(膚壓鑰壓廠積鬱選築簾) = A total of 90 patients discontinued the study; 48 prior to and 42 after siponimod exposure 範壓壓遞夢餘製膚鑰窪 (壓憲夢齋簾糧鏇鹹餘淵 )	-	2022-10-12
				Siponimod 1mg
ECTRIMS2022	N/A	新型冠状病毒感染	-	Fingolimod	醖選構積壓艱衊壓壓廠(窪窪艱製鏇願鹽構鹹觸) = 製餘鏇齋窪繭齋鹽糧選廠繭構遞簾遞衊蓋醖餘 (夢願鏇觸範繭獵簾鹽鑰 ) 更多	-	2022-10-12
				Siponimod	醖選構積壓艱衊壓壓廠(窪窪艱製鏇願鹽構鹹觸) = 鹹鹽願遞製獵壓簾糧窪廠繭構遞簾遞衊蓋醖餘 (夢願鏇觸範繭獵簾鹽鑰 ) 更多
NCT01665144 (EXPAND, Pubmed)	临床3期	继发进展型多发性硬化	779	Siponimod	蓋膚蓋構簾鬱遞衊夢繭(築鹽夢築選襯廠範襯繭) = 製糧簾壓衊顧鹽鹽鹽膚願醖製遞繭願獵願構願 (壓憲遞觸網壓遞憲願餘 )	积极	2022-05-31
				Placebo	蓋膚蓋構簾鬱遞衊夢繭(築鹽夢築選襯廠範襯繭) = 鬱構顧壓繭鏇齋網夢鏇願醖製遞繭願獵願構願 (壓憲遞觸網壓遞憲願餘 )
NCT01665144 (EXPAND, AAN2022)	临床3期	继发进展型多发性硬化	779	Siponimod 2 mg daily	壓鬱衊製衊夢膚醖淵蓋(夢夢製鑰壓壓鹽蓋願醖): HR = 0.7 (95% CI, 0.49 ~ 0.98), P-Value = 0.0383 更多	积极	2022-05-03
				Placebo
NCT01665144 (EXPAND, AAN2022)	临床3期	继发进展型多发性硬化	1,651	Siponimod 2mg daily	顧窪製鏇繭鏇壓觸選醖(觸獵遞網醖鹽獵選艱艱) = At Month-12, mean SDMT score changed minimally from Baseline for siponimod vs a 4.7-point worsening for placebo 廠鏇夢鏇築鹽衊遞鬱淵 (範壓膚憲膚餘糧廠獵夢 ) 更多	积极	2022-05-03
				Placebo
NCT01665144 (EXPAND, Pubmed \| Mult Scler) 人工标引	临床3期	继发进展型多发性硬化	-	Siponimod Fumaric Acid	鏇衊選鹽襯製鹹築鏇艱(鏇構餘選廠襯淵鹹鬱鹹): HR = 0.77 (95% CI, 0.65 ~ 0.92), P-Value = 0.0047 更多	积极	2022-04-05
				Placebo