Spesolimab

-01-引言：靶向治疗的黄金时代自身免疫性疾病（如银屑病、类风湿关节炎、系统性红斑狼疮等）以免疫系统失调为特征，全球患者群体庞大且治疗需求迫切。在过去的25年里，通过调节细胞因子信号来靶向免疫系统一直是自身免疫性疾病治疗创新的基石，例如英夫利昔单抗和阿达木单抗等肿瘤坏死因子（TNF）抑制剂的成功，它们已成为多种适应症的标准治疗方法。随着白细胞介素（IL）抑制剂以及参与细胞因子受体下游信号传导的激酶抑制剂（如Janus酪氨酸激酶）的成功，人们对细胞因子调节的兴趣进一步扩大。近年来IL-13、IL-31、IL-36和TYK2等新靶点的崛起，标志着行业进入精准化与多样化的新阶段。2022年全球TOP100畅销药合计实现了4868亿美元的销售收入，自免疾病领域已经是仅次于肿瘤的第二大药物市场。跻身TOP100榜单的自免产品共18款，总金额达861.7亿美元。如今，自免领域已成为重磅炸弹的密集诞生地，也成为各大制药巨头业绩贡献的主要来源。-02-一、靶点全景扫描：2024年Top 15靶点与竞争格局 根据2024年最新数据，自身免疫疾病领域进入II/III期或已上市的药物靶点中，TNF超家族成员、IL家族及下游激酶（JAK/TYK2）仍是核心方向，但新兴靶点的崛起正在重塑行业版图。自2020年以来，已经推出了四种治疗自身免疫性疾病的first-in-class药物，其中三种针对皮肤病适应症中的上皮屏障功能障碍和炎症（IL-13、IL-31和IL-36抑制剂）。第四种也是在皮肤病学中，是酪氨酸激酶2（TYK2）抑制剂，它调节细胞因子如IL-12和IL-23下游的信号传导。在分析的92个治疗靶点中，正在研究的自身免疫性疾病药物数量从2020年的131种增加到2024年的193种。最显著的进展发生在靶向TNF超家族成员而非TNFα的药物上：虽然CD40/CD40配体轴是2020年III期的唯一靶点，但靶点包括OX40、TNF样配体1A（TL1A）、核因子κβ受体激活剂（RANK）、B淋巴细胞刺激剂（BLyS）和B细胞活化因子（BAFF）的药物在2024年均进入III期试验。白细胞介素靶向药物的创新包括药理学的选择性增强（如IL-17A/F抑制剂）、活性延长（如GSK的长效IL-5抑制剂depemokimab）和创新技术（如礼来的口服小分子靶向IL-17）。First-in-class的药物包括靶向IL-4、IL-33和IL-18。靶向IL-1受体相关激酶4（IRAK4）引起了人们广泛的兴趣，因为它有可能用单一药物抑制整个IL-1家族（IL-1、IL-18、IL-33和IL-36；涉及银屑病和哮喘）和toll样受体。靶向胸腺基质淋巴细胞生成素（TSLP）也引起了人们的关注，因为它解决了2型炎症的上游驱动因素（IL-5、IL-4和IL-13）。在免疫级联的下游，参与银屑病和克罗恩病的IL-12和IL-23途径的TYK2抑制剂正在积极推进，因为与JAK抑制剂相比，它们避免了对造血系统的影响。联合策略，如共同靶向IL-17和TNF或双激酶抑制剂（JAK1、2或3与TYK2、SYK或TEC），正在进一步扩大治疗选择。-03-二、跨疾病影响：从皮肤病到系统性疾病的全线突破自2020年以来，皮肤病学取得了最大的进步，推出了几种新型药物。其中包括两种IL-13抑制剂tralokinumab（Adtralza；LEO Pharma）和lebrikizumab（Ebglyss；Lilly）用于治疗中度至重度特应性皮炎；IL-17A/F选择性抑制剂bimekizumab（Bimzelx；UCB）用于治疗斑块状银屑病，IL-31抑制剂nemolizumab（Nemluvio；Galderma）用于治疗结节性痒疹，IL-36抑制剂spesolimab（Spevigo；Boehringer Ingelheim）用于治疗泛发性脓疱性银屑病。还推出了用于银屑病的选择性TYK2抑制剂（Sotyktu；百时美施贵宝）和第一种用于脱发的JAK3/TEC抑制剂（Litfulo；辉瑞）。  JAK抑制剂继续扩大其治疗范围，特别是在风湿病适应症中，如强直性脊柱炎和类风湿性关节炎。随着选择性JAK1抑制剂的使用越来越多，以及针对嗜酸性食管炎的IL-4/IL-13靶向疗法的引入，胃肠道疾病也出现了创新。呼吸系统疾病的进展包括推出首个针对TSLP的药物tezepelumab（Tezspire；阿斯利康/安进）用于治疗严重哮喘，以及首次批准用于治疗慢性阻塞性肺疾病（COPD）的生物制剂dupilumab（Dupixent；赛诺菲）。创新治疗的最大竞争是针对2型炎症性疾病，如特应性皮炎、慢性痒疹、慢性荨麻疹、哮喘和伴有鼻息肉的慢性鼻窦炎。IL-5、效应细胞因子（IL-4、IL-13）、警报素细胞因子（TSLP、IL-25、IL-33）、IgE、IL-31、BTK和JAK是关键靶点。-04-三、未来展望：精准医疗与多维度创新自身免疫管线预计在未来几年将提供几种first-in-calss的疗法。在皮肤病学领域，安进的罗卡替尼和赛诺菲的氨利替尼是针对OX40/OX40L T细胞活化轴的新型药物，有望解决IL-4和IL-13产生的关键上游调节因子。预计慢性阻塞性肺病也将受益于一种新的治疗类别，有两种针对IL-33的竞争性候选药物：itepekimab（赛诺菲）和双重IL-33/IL-1受体样1（ST2）抑制剂tozorakimab（阿斯利康）。此外，CD40/CD40L轴可能会为系统性疾病引入新的治疗替代方案，包括用于干燥综合征的dazodalibep（安进）和用于系统性红斑狼疮的dapirolizumab（Biogen/UCB）。克罗恩病和溃疡性结肠炎可能受益于一种新的药物类别，该药物类别有三种针对TL1A的候选药物：默克公司的tulisokibart和罗氏/Roivant的RVT-3101目前处于III期，赛诺菲/Teva的duvakitug正在进入III期。 制药行业必须应对治疗策略中药物定位的复杂挑战，包括临床研究中治疗比较物的选择、联合疗法和生物标志物驱动的患者细分。药物之间的区别将取决于作用机制和创新的药物设计，例如提高靶点选择性和耐受性，口服小分子和注射细胞因子抑制剂之间治疗方案的便利性，特别是在考虑长效与短效药物制剂的情况下。目前，对于率先上市的药物（针对TL1A、OX40、TSLP、IL-33和TYK2等靶点）、first-in-class的创新（如对IL-17、IL-23和JAK抑制剂的选择性增强）和多适应症机会（如针对2型炎症性疾病中的IL-4/13和IL-5抑制剂）的竞争加剧。这些进展预示着治疗自身免疫性疾病的新时代的到来。-05-四、自身免疫疾病的全球和中国市场经统计，全球自身免疫疾病治疗药物处于稳定增长的趋势。弗若斯特沙利文数据显示，全球自身免疫疾病药物市场预计将由2021年的1,277亿美元，增长至2030年的1760亿美元，复合年增长率为3.6%。2021年，自身免疫疾病生物制剂市场规模为891亿美元，预计到2030年将增至1421亿美元，分别占2021年及2030年全球自身免疫疾病药物市场的69.8%及80.8%。来源：弗若斯特沙利文报告鉴于中国庞大的患者群体及自身免疫疾病创新疗法的进步，中国自身免疫疾病药物市场有望快速增长，由2017年的17亿美元增长至2021年的30亿美元，复合年增长率为15.2%，估计2030年将达到231亿美元，2021年至2030年复合年增长率为25.5%。估计生物药在中国自身免疫疾病中的份额将由2021年的32.9%增加至2030年的71.8%。来源：弗若斯特沙利文报告虽然中国的自免市场在快速增长，但潜力仍未完全发掘。一方面是由于中国自免药物市场仍以传统小分子为主导，而进口自免新药已进入中国，但众多的自免患者由于分布在经济欠发达地区，支付能力仍有限。另一方面，则由于自免疾病作为慢性病并不致死，导致患者认知程度不高，因此，该领域许多疾病的诊断和治疗率一直很低。不过，随着治疗手段的升级，疗效更好的生物制剂逐渐将被医生和患者所接受。而中国创新药的崛起也将凭借价格优势覆盖更广泛的患者群体。此外，银屑病、特应性皮炎、系统性红斑狼疮等自免疾病主要影响年轻群体，这类新生代人群更注重个人生活品质的提高，对身体、形象的受损容忍度低，因此有更强的支付意愿。多种有利因素将促进中国自免市场规模的快速增长。-06-结语自身免疫疾病的药物研发正经历从“广谱抗炎”到“精准调控”的范式转变。未来十年，随着疾病特异性机制解析、多组学技术及新型递送系统的突破，我们将见证更多创新靶点被攻克，患者将迎来更安全、长效且个体化的治疗方案。中国凭借庞大的患者基数、快速发展的生物医药产业和政策支持，正在重塑全球市场格局。随着IL-17抑制剂、JAK抑制剂等药物的普及，更多人将实现"疾病控制"到"临床治愈"的跨越。期待中国创新力量在自身免疫治疗领域继续书写传奇。参考文献：1.The multifunctional protein HMGB1: 50 years of discovery. Nat Rev Immunol. 2023 Jun 15.2. Trends in the drug target landscape for autoimmune diseases. Nat Rev Drug Discov.2025 Apr 3公众号内回复“ADC”或扫描下方图片中的二维码免费下载《抗体偶联药物：从基础到临床》的PDF格式电子书！公众号已建立“小药说药专业交流群”微信行业交流群以及读者交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。

Improvements in Psoriasis Symptom Scale (PSS), Pain Visual Analog Scale (VAS) and Dermatology Life Quality Index (DLQI) scores were observed in post-hoc exploratory analyses of the EFFISAYIL® 2 trial Findings suggest the potential benefit of continuously treating generalized pustular psoriasis (GPP) with subcutaneous spesolimab RIDGEFIELD, Conn., March 7, 2025 /PRNewswire/ -- Today, Boehringer Ingelheim announced new analyses to be presented at the American Academy of Dermatology (AAD) annual meeting in Orlando that explore the effect that SPEVIGO® (spesolimab-sbzo) may have on the physical symptoms and mental health burden associated with generalized pustular psoriasis (GPP). These post-hoc exploratory analyses from the EFFISAYIL® 2 clinical trial assessed the efficacy and safety of subcutaneous SPEVIGO in patients suffering from GPP.1,2 Distinct from plaque psoriasis, GPP is a serious and rare, chronic, heterogenous, inflammatory neutrophilic disease associated with painful skin manifestations and systemic symptoms, such as fever, pain, and fatigue.3-6 GPP's unpredictable nature can potentially have significant long-term impacts on quality of life for people living with it and may cause fear and anxiety over the disease course.5,7 "Generalized pustular psoriasis profoundly affects patients' physical and mental well-being, often disrupting their education, careers, and personal relationships. We are encouraged by the improvements observed in patient-reported outcomes with spesolimab. These studies strengthen our commitment to delivering innovative treatments for those living with severe dermatological conditions like GPP," says Vicky Brown, Senior Vice President and Head of Immunology, Oncology, and Eye Health, Boehringer Ingelheim Pharmaceuticals, Inc. In the EFFISAYIL 2 clinical trial, patients with a history of GPP were randomized to receive one of three active treatment regimens or a placebo. Participants were asked to rate their GPP symptoms – including pain, redness, itching, and burning – using the Psoriasis Symptom Scale (PSS), the Pain Visual Analog Scale (VAS), and the Dermatology Life Quality Index (DLQI). The PSS ranges from 0 to 16, while the Pain VAS ranges from 0 to 100, with higher scores indicating more severe symptoms. Of the 30 patients randomized to receive subcutaneous spesolimab, 300 mg every four weeks after a 600mg loading dose, participants reported a reduction in mean Pain VAS scores over the course of the trial, with more than half (56.5%) of patients reporting a Pain VAS score of 0 at Week 48 and the mean PSS score decreasing from 5.34 to 2.96 by Week 48. Patients were also asked to rate the impact of GPP through a 10-item questionnaire to assess changes in quality of life using the DLQI. The results found that mean DLQI scores improved from a "very large effect on patient's life" score (11.14) at baseline to a "small effect on patient's life" score (4.57) at week 48 following treatment with SPEVIGO. Measurable improvements in mean PSS, Pain VAS and DLQI scores were observed by the first assessment at Week 4. "The results from EFFISAYIL 2 provide valuable insights into the chronicity of generalized pustular psoriasis," said Dr. Tina Bhutani, study author. "The data are a pivotal step in advancing patient-centered care in GPP." These findings may provide healthcare professionals with data that can help inform their choice of treatment regimens for people living with GPP. About SPEVIGO® SPEVIGO® is a novel, humanized, selective antibody that specifically blocks the activation of the IL-36R, a signaling pathway within the immune system shown to be involved in the pathogenesis of several autoinflammatory diseases, including GPP. It is the first targeted therapy for the treatment of GPP and has been evaluated in the largest clinical program specifically for the treatment of patients with GPP. What is SPEVIGO®? SPEVIGO® is a prescription medicine used to treat generalized pustular psoriasis (GPP) in adults and children 12 years of age and older who weigh at least 88 pounds (40 kg). It is not known if SPEVIGO® is safe and effective in children under 12 years of age or who weigh less than 88 pounds (40kg). Important Safety Information Do not receive SPEVIGO® if you or your child have had a severe or life-threatening allergic reaction to spesolimab-sbzo or any of the ingredients in SPEVIGO®. What is the most important information I should know about SPEVIGO®? SPEVIGO® may cause serious side effects, including: Infections. SPEVIGO® may lower the ability of your or your child's immune system to fight infections and may increase your or your child's risk of infections. Your healthcare provider should check you or your child for infections and tuberculosis (TB) before starting treatment with SPEVIGO® and may treat you or your child for TB before you begin treatment with SPEVIGO® if you have a history of TB or have active TB. Your healthcare provider should watch you or your child closely for signs and symptoms of TB during or after treatment with SPEVIGO®. Tell your healthcare provider right away if you or your child have an infection or have symptoms of an infection during or after treatment with SPEVIGO®, including: fevers, chills, or sweats muscle aches cough shortness of breath blood in your phlegm (mucus) burning when you urinate urinating more often than normal Allergic reactions and infusion-related reactions. Serious allergic reactions may happen during or after your or your child's SPEVIGO® injection. If you or your child have a serious allergic reaction, your healthcare provider will stop treatment with SPEVIGO®. If you or your child are given SPEVIGO® in a vein (intravenously) and have an infusion- related reaction, your healthcare provider will stop your or your child's SPEVIGO® infusion and treat your or your child's symptoms and may restart SPEVIGO® at a slower infusion rate. Tell your healthcare provider or get emergency medical help right away if you or your child get any of the following symptoms during or after your or your child's SPEVIGO® injection: feeling faint, dizzy, or lightheaded swelling of your face, eyelids, lips, mouth, tongue, or throat trouble breathing or throat tightness fever mouth sores chest tightness hives or skin rash that is different than the rash from generalized pustular psoriasis (GPP) itching swollen lymph nodes Before you or your child receive SPEVIGO®, tell your healthcare provider about all of your medical conditions, including if you or your child: have an infection that does not go away or that keeps coming back. have TB or have been in close contact with someone with TB. have recently received or are scheduled to receive an immunization (vaccine). You or your child should not receive live vaccines during and for at least 16 weeks after treatment with SPEVIGO®. You or your child should be brought up to date with all vaccines before starting SPEVIGO®. are pregnant or plan to become pregnant. It is not known if SPEVIGO® can harm your or your child's unborn baby. are breastfeeding or plan to breastfeed. It is not known if SPEVIGO® passes into your breast milk. Talk to your healthcare provider about the best way to feed your or your child's baby during treatment with SPEVIGO®. Tell your healthcare provider about all the medicines you or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What are the possible side effects of SPEVIGO®? The most common side effects of SPEVIGO® given in a vein (intravenously) for GPP flare treatment include: feeling tired or weak nausea and vomiting headache itching or itchy bumps a collection of blood under the skin at the infusion site or bruising urinary tract infection The most common side effects of SPEVIGO® when given under the skin (subcutaneously) for treatment of GPP when not experiencing a flare include: redness, pain, swelling, hardening, hives, or warmth at the injection site joint pain urinary tract infection itching These are not all of the possible side effects of SPEVIGO®. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1 ‐ 800 ‐ FDA ‐ 1088. Please see full Prescribing Information , Medication Guide, and Instructions for Use . About the EFFISAYIL® clinical trial program The EFFISAYIL® clinical trial program evaluated the largest and broadest population of GPP patients in trials of a therapy specifically targeting the IL-36 pathway for GPP: EFFISAYIL® 1: A Phase II study that demonstrated treatment with a single intravenous dose of spesolimab significantly improved signs and symptoms of GPP in patients experiencing a flare, including rapid pustular and skin clearance. These results supported the approval of spesolimab as the first specific treatment for GPP flares in adults in major markets EFFISAYIL® 2: A Phase IIb study that showed spesolimab significantly reduced the risk of GPP flares by 84% over 48 weeks compared to placebo. In the trial with 123 patients, no flares were observed after week 4 of spesolimab SC treatment in the high-dose group (n=30) EFFISAYIL® ON: An open-label extension study to evaluate the long-term safety and efficacy of spesolimab in patients with GPP who have completed previous spesolimab trials About generalized pustular psoriasis GPP is a chronic, heterogenous, neutrophilic inflammatory disease associated with skin and systemic symptoms that is distinct from plaque psoriasis. GPP is recognized as a separate clinical entity from other forms of psoriasis, with the IL-36 pathway being a key driver of GPP and triggering response to treatment. Prevalence of GPP is low and varies considerably across geographical regions, ranging from 1.76 to 124 patients per million persons in reports from key countries, including France, Japan, Sweden, and South Korea. GPP can become life-threatening (mortality rates ranging from 2% to 16%) due to severe complications, such as multisystem organ failure and sepsis requiring urgent hospital care; many GPP patients also suffer from various comorbidities, which contribute to the ongoing burden for the patient and healthcare systems. GPP symptoms appear unpredictable and present on a continuum, which greatly impacts a patient's quality of life, and may cause fear and anxiety over the disease course, as well as long-term impacts on quality of life related to work/school, emotional health, social activities, and finances. About Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry's top investors in Research and Development, the company focuses on developing innovative therapies in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. Learn more at . 1Bhutani T, et al. Spesolimab improves quality of life as measured by Psoriasis Symptom Scale (PSS) and Pain Visual Analog Scale (VAS) in generalized pustular psoriasis (GPP) over time: Results from the EFFISAYIL® 2 trial. Poster presented at 2025 AAD Annual Meeting; March 2025; Orlando. 2Gordon K, et al. Spesolimab improves quality of life as measured by Dermatology Life Quality Index (DLQI) in generalized pustular psoriasis (GPP) over time: Results from the EFFISAYIL® 2 trial. Poster presented at 2025 AAD Annual Meeting; March 2025; Orlando. 3Marrakchi S, Puig L. Pathophysiology of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23:13–19. 4Strober B, et al. Dermatol Ther. (Heidelb) 2021;11:529–41. 5Prinz JC, Choon SE, Griffiths CEM, et al. Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review. J Eur Acad Dermatol Venereol. 2023;37:256–273. 6Reisner DV, Johnsson FD, Kotowsky N, et al. Impact of generalized pustular psoriasis from the perspective of people living with the condition: Results of an online survey. Am J Clin Dermatol. 2022;23:65–71. 7Gooderham MJ, Van Voorhees AS, Lebwohl MG. An update on generalized pustular psoriasis. Expert Rev Clin Immunol. 2019;15:907–919. Media Contact Jennifer Huron Boehringer Ingelheim Pharmaceuticals, Inc. Phone: +1 203-448-1263 Email: [email protected] SOURCE Boehringer Ingelheim WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED