Frexalimab

近日，赛诺菲（Sanofi）与梯瓦（Teva Pharmaceuticals）宣布双方共同开发的用于炎症性肠病（IBD）的在研单抗duvakitug在临床IIb期研究RELIEVEUCCD中达到了主要终点，并展现出“best-in-class”疗法的潜力。 2023年10月4日，赛诺菲以5亿美元的首付款及最高达10亿美元的里程碑付款与梯瓦就该药的开发和商业化达成了合作，交易总金额高达15亿美元（约合109.46亿人民币）。 109亿下注，赛诺菲瞄准千亿自免市场。   01   重磅疗法结果亮眼 12月17日，赛诺菲和梯瓦宣布duvakitug 的IIb期RELIEVE UCCD研究达到了主要终点。结果显示，相比于安慰剂，duvakitug治疗组的患者获得了更高的临床缓解率，显示出“best-in-class”疗法的潜力（图1）。 图1.Duvakitug IIb期结果显示在uc和CD中具有“best-in-class”的潜力 Duvakitug（TEV’574）是一款潜在“best-in-class”的人源化IgG1-λ2单克隆抗体，靶向肿瘤坏死因子（TNF）样配体1A（TL1A），也称为TNF超家族成员15。TL1A通过与死亡受体3（DR3）结合，可放大炎症反应并驱动IBD相关纤维化的进展。靶向TL1A有望缓解IBD患者的过度免疫反应。因此，利用duvakitug靶向TL1A可能会减轻IBD疾病中过度活跃的免疫反应（图2）。duvakitug目前正处于治疗UC和CD（两种最常见的IBD类型）的2b期临床研究中。 图2.Duvakitug作用机制 RELIEVE UCCD是一项为期14周的随机、双盲、剂量递增IIb期研究，旨在评估duvakitug在中重度UC或CD成人患者中的疗效、安全性、药代动力学和耐受性。符合入组标准的患者按1:1:1的比例随机分配接受每两周一次皮下注射的两种剂量的duvakitug或安慰剂治疗。主要疗效终点是UC队列中显示临床缓解的受试者人数或CD队列中显示内镜缓解的受试者人数。 结果显示，在UC队列中，duvakitug低剂量组、高剂量组与安慰剂组分别有36.2%、47.8%、20.45%的患者实现了临床缓解，duvakitug两个剂量组经安慰剂校正后的临床缓解率分别为15.7%（p=0.050）和27.4%（p=0.003），差异显著；在CD队列中，三个治疗组的内镜缓解率分别为26.1%、47.8%、13.0%，duvakitug两个剂量组经安慰剂校正后的内镜缓解率分别为13.0%（p=0.058）和34.8%（p<0.001），数据具显著差异。总体而言，各患者亚组间的治疗效果一致。此外，duvakitug在UC和CD患者中显示出良好的耐受性，未发现安全性信号。duvakitug组和安慰剂组的治疗相关不良事件（AE）总体发生率相当，均为50%。 此次duvakitug的潜在突破，再次表明赛诺菲在自免领域的领导雄心！   02   百亿单品问世 实际上，自免领域向来是赛诺菲的核心领域之一。长期以来，赛诺菲在该领域凭借深厚的研发积淀、卓越的科研实力以及一系列成功的产品，占据着举足轻重的地位，成为其在医药行业的一张王牌（表1）。 表1.赛诺菲自免领域上市产品 赛诺菲2023年营收465.2亿美元，其中自免业务营收121.0亿美元，占比26%。其中，重磅产品Dupixent表现可谓十分亮眼，作为全球首个获批上市的IL-4Rα靶向单抗，2023年销售额高达115.7亿美元，跻身百亿美元单品行列。预计2023-2030年间将保持低双位数的增速增长。 2024年10月25日，赛诺菲发布了2024年第三季度财务业绩。其中，Dupixent销售额34.76亿欧元（约36亿美元），同比增长23.8%；Dupixent前三季度销售额达96.14亿欧元（约99.58亿美元），同比增长25.9%。公司预测，2024年全年，Dupixent销售收入可达130亿欧元（图3）。据公开资料整理，24年Dupixent前三季度销售额已经超越修美乐（73.11亿美元），荣升全球自免新王。 图3.Dupixent历年销售额 Dupixent让赛诺菲在自免域拥有着重要的地位。在中国，自2020年获批上市后，度普利尤单抗至2023年11月已经拿下了6项适应证。此外，Dupixent在国内2020年首次进入医保（降价52.6%），2023年以2780元/支续约成功，2022年国内销售额8.7亿元（+179.3%）。   03   百亿爆款后继有人 此外，赛诺菲在自免领域拥有多款在研产品，据2023年底赛诺菲在全球投资者研发日信息，赛诺菲研发管线中有12款新分子实体具有成为重磅药物的潜力（图4），其中，9款为创新药物和疫苗，包括治疗多发性硬化的Tolebrutinib、治疗哮喘的Lunsekimig和Rilzabrutinib、治疗炎症性肠病的TL1A单抗、治疗特应性皮炎的IRAK4降解剂和治疗COPD的Itepekimab，每款峰值销售潜力有望达到20亿至50亿欧元；还有三款为“自成管线产品”Amlitelimab、Frexalimab和SAR441566（口服TNFR1si），每款峰值销售潜力有望超过50亿欧元。  图4.赛诺菲研发管线中具有重磅潜力的新分子实体 在这些在研产品中，Amlitelimab是目前进展最快的OX40L单抗，Amlitelimab是一款潜在“best-in-class”OX40信号通路阻断剂，有潜力12周给药一次治疗特应性皮炎，可显著减少患者的治疗负担。在全球范围内，研究人员正在多项2期和3期临床研究中评估amlitelimab的临床应用潜力，包括针对不同治疗背景的特应性皮炎受试者（图5）。 图5.Amlitelimab介绍 Frexalimab （CD40L）第一个高效、非淋巴细胞耗竭方式治疗多发性硬化症的新型疗法，Frexalimab是一款靶向CD40L的单克隆抗体。该产品此前已经在治疗多发性硬化的II期临床研究中达到主要终点（图6），目前在3期临床中，预计最快2027年上市。 图6.Frexalimab治疗多发性硬化的II期临床试验结果 SAR441566是一款口服TNFR1抑制剂，能够选择性抑制TNFR1，不会影响TNFR2信号通路传导，具有更好的安全性。Ib临床中表现出很好的安全性，2025年将会发布银屑病和类风湿关节炎的IIb期数据。有望成为关节炎/炎症性肠病等大自免适应症的口服疗法（图7）。 图7.SAR441566介绍 Lunsekimig是一款将靶向IL-13和靶向TSLP的重链可变区（VHH）连接在一起的纳米抗体（图8）。IL-13和TSLP都是在I&I领域已经经过验证的靶点，同时抑制这两条信号通路可能产生协同作用，产生更强的疗效。在治疗哮喘患者的1b期临床试验中，lunsekimig与靶向IL-13或靶向TSLP的单药疗法相比，显著改善患者的呼出一氧化氮分数（FeON），这是一个反映气道炎症的指标。这一结果显示阻断这两条信号通路的潜在协同作用。 图8.Lunsekimig介绍 赛诺菲在自免领域展现出了强劲的发展势头，其众多重磅在研产品线无疑是公司未来发展的强大引擎，百亿爆款后继有人！ 参考资料 [1]https://www.sanofi.com/en/media-room/press-releases/2024/2024-12-17-12-30-00-2998154 [2]https://s24.q4cdn.com/720828402/files/doc_presentations/2023/10/TL1A-Teva-Presentation-2023-10-04-website.pdf [3]https://www.sanofi.com/assets/dotcom/content-app/events/quaterly-results/2023/2023-q3-2023-results/q3-2023-presentation-en.pdf [4]https://www.sanofi.com/assets/dotcom/content-app/events/investor-presentation/2023/r-and-d-day-2023/Presentation.pdf [5]赛诺菲官网，各种公开资料。 识别微信二维码，可添加药时空小编 请注明：姓名+研究方向！

DUBLIN--( BUSINESS WIRE )--The "CD40 Targeted Therapies Clinical Trials, Therapeutic Approaches & Market Opportunity Insight 2025" report has been added to ResearchAndMarkets.com's offering. CD40 targeted therapies have become a focal point in immunotherapy research, with growing attention on harnessing the potential of the CD40 receptor to treat a variety of diseases. While no CD40 targeted therapies have yet been approved for clinical use, some promising candidates are currently undergoing late stage clinical development. Moreover, additional candidates are slated to enter late-stage trials within the next year, expanding the pool of CD40 targeted therapies in clinical development. These ongoing research and clinical trials suggest that CD40 targeted therapies could become a vital treatment option for patients with prevalent diseases in the coming years. Global CD40 Targeted Therapies Clinical Trials, Therapeutic Approaches & Market Opportunity Insight 2025 Report Highlights: First CD40 Targeted Therapy Approval Expected By 2027 CD40 Targeted Therapies In Clinical Trials: > 20 Therapies CD40 Inhibitors Clinical Trials Insight By Company, Country, Indication & Phase CD40 Targeted Therapy Research & Development Trends By Indication CD40 Targeted Therapy Market Trend Analysis By Region CD40 Targeted Therapies Proprietary Technologies By Company Historically, the primary focus of CD40 targeted therapies has been on autoimmune and inflammatory diseases. However, there is an increasing interest in exploring their potential for treating cancer and other conditions. More recent studies have expanded the scope of CD40 targeting to include infectious diseases, such as HIV and COVID-19, as well as neurodegenerative diseases like Alzheimer's and Parkinson's disease. Some research has also suggested that CD40 targeted therapies might be beneficial for diseases like cardiovascular conditions, where CD40's signaling pathway, although not directly involved in disease initiation, plays a role in disease progression and inflammation. Over the years, various strategies have been employed to target the CD40 receptor and its ligand. These include traditional monoclonal antibodies as well as next-generation molecular therapeutics such as small interfering RNA (siRNA). While antibodies are developed either as CD40 agonists or as antagonists, CD40 targeted siRNAs aim to reduce CD40 protein expression by degrading CD40 mRNA. Several other conventional and next-generation approaches are undergoing active research and clinical trials to assess their safety and efficacy. Nonetheless, antibody therapies remain the dominant approach in CD40 targeted research. Among the most advanced CD40/CD40L targeted antibodies are those for autoimmune and inflammatory diseases, with some entering phase 3 clinical trials. For example, Sanofi's Frexalimab, a promising anti CD40 antibody, is currently in phase 3 trials for autoimmune conditions. In the cancer domain, CD40 targeted antibodies are also making significant strides, with companies like Alligator Bioscience preparing to initiate phase 3 clinical trials for its lead candidate, mitazalimab, an anti-CD40 antibody for pancreatic ductal adenocarcinoma (PDA) and pancreatic cancer. The development of CD40 targeted therapies has been greatly facilitated by the advent of proprietary technologies and platforms. One notable example is GenMab's DuoBody platform, which enables the creation of bispecific antibodies that can target two different antigens simultaneously. This technology has been leveraged to develop several promising immunotherapies, including its CD40 targeted therapy, GEN1042/BNT312, currently in phase 2 trial for malignant solid tumors. As the field of CD40 targeted therapies evolves, the competitive landscape is becoming increasingly crowded, with many major pharmaceutical companies entering the arena. Notable players include Amgen, Sanofi, GenMab, BioNTech, and Biogen, all of which are investing heavily in this space. Collaborations between pharmaceutical companies and academic institutions have been essential in advancing the scientific understanding of CD40 targeted therapies, combining cutting edge research with clinical expertise to bring these therapies closer to market. In conclusion, while CD40 targeted therapies have not yet been approved for clinical use, they represent a promising and rapidly developing area of research across a wide range of diseases. As more therapies enter clinical trials and the competitive landscape intensifies, it is clear that CD40 targeted therapies could become a cornerstone of treatment for cancer, autoimmune diseases, infectious diseases, and beyond in the near future. Key Topics Covered: Introduction To CD40 Targeted Therapies Considering CD40 As Drug Target Over Other CD Markers History & Evolution Of CD40 Targeting Therapies CD40 Targeted Therapies - Mechanism Of Action Agonist Mediated Activation Of CD40 Signaling Antagonist-Mediated Inhibition Of CD40 Signaling CD40 Targeted Therapeutic Approaches Antibody Formats Fusion Proteins Peptides Nucleic Acids CD40 Targeted Therapy Research & Development Trends By Indication Cancer Neurological Diseases Autoimmune & Inflammatory Disorders Transplant Rejection Microbial Infections Global CD40 Targeted Therapy Market Outlook Current Market Trends & Developments Future Market Opportunities CD40 Targeted Therapy Market Trend Analysis By Region US Europe China Japan Australia CD40 Targeted Therapies Clinical Trials Insight By Company, Country, Indication & Phase Research Preclinical Phase I Phase I/II Phase II Phase III CD40 Targeted Therapies - Proprietary Technologies By Company Alligator Bioscience - FIND Technology & Neo-X-Prime Aprilbio - SAFA Platform Biocytogen - RenMice EnnoDC - Unnamed Platform Genmab - DuoBody Harbour BioMed - Harbour Mice & HBICE Kyowa Kirin - REGULGENT Strike Pharma - ADAC Technology Platform Global CD40 Targeted Therapy Market Dynamics Competitive Landscape Alligator Bioscience Amgen Biogen BioNTech Eledon Pharmaceuticals EnnoDC Genmab Innovent Bio Novartis Sanofi Tonix Pharmaceuticals UCB For more information about this report visit https://www.researchandmarkets.com/r/46sm5e About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. 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