Recurrent implantation failure (RIF), defined as the absence of clinical pregnancy after the transfer of three good-quality embryos, concerns up to 40% of IVF couples and is associated with a low success rate. The causes remain unexplained in over 50% of cases.
Various dysimmune changes (related to immune T cells profiles, pro-inflammatory cytokines levels) have been described in unexplained RIF as compared to fertile controls, and it has been estimated that such dysimmunity may occur in 50% of unexplained RIFs. Previous data on a benefit of general immune modulation by steroids or immunoglobulins are heterogenous and failed to demonstrate clinically significant benefit. The proinflammatory cytokine Tumor Necrosis Factor (TNF) α participates in the regulation of the immune balance of the endometrium, its peripheral blood and endometrial concentrations are increased in RIF patients as compared to fertile controls. In 2009, a pilot placebo controlled study showed that TNF-α antagonist treatment allowed a 56% live birth rate (versus 13% in controls) in 13 women with unexplained RIF. Due to the lack of maternal and fetal tolerance data, TNF-α antagonists were not further evaluated. Today, safety data issued from 1200 pregnancies are reassuring allowing the use of TNF-α antagonists during pregnancy (www.lecrat.org). In addition the TNF-α antagonist certolizumab does not cross the placental barrier.
We hypothesize that certolizumab may improve clinical pregnancy rates in women with unexplained RIF with a good safety profile.

开始日期2023-11-30

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

NCT06028438 / Active, not recruiting临床2期

A Phase 2a Multicenter, Randomized, Double Blind, Parallel, Proof of Concept Study Evaluating the Efficacy and Safety of Nipocalimab and Certolizumab Combination Therapy in Participants With Active Rheumatoid Arthritis Despite Prior Treatment With Advanced Therapies (bDMARD or tsDMARD)

The purpose of this study is to evaluate the efficacy of combination therapy with nipocalimab and certolizumab compared to certolizumab monotherapy.

开始日期2023-08-15

申办/合作机构

Janssen Research & Development LLC

NCT05115903 / Active, not recruiting临床4期IIT

A Prospective, Randomized Biologic Tapering Study of TNF Inhibitors in Axial Spondyloarthritis

Current evidence on tapering of tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) is still hampered by heterogeneity in tapering regimens, selection and performance biases, and lack of data on optimized treatment dosing strategies especially in real-world clinical settings. This study aims to contribute to the ongoing investigation of disease-activity-guided tapering of TNFi in axSpA in the form of a prospective, randomized controlled trial.

开始日期2021-12-01

申办/合作机构

University Health Network

100 项与培塞利珠单抗相关的临床结果

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100 项与培塞利珠单抗相关的转化医学

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100 项与培塞利珠单抗相关的专利（医药）

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项与培塞利珠单抗相关的文献（医药）

2024-12-01·ANNALS OF THE RHEUMATIC DISEASES

Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial

Article

作者: Wolbink, Gertjan ; Nurmohamed, Michael T ; Nordström, Dan C ; Østergaard, Mikkel ; Rispens, Theo ; Hørslev-Petersen, Kim ; Heiberg, Marte Schrumpf ; Frazzei, Giulia ; Sokka-Isler, Tuulikki ; Lend, Kristina ; Lampa, Jon ; Haavardsholm, Espen A ; Twisk, Jos W R ; Rudin, Anna ; Grondal, Gerdur ; van Vollenhoven, Ronald F ; Padyukov, Leonid ; Christiaans, Jeroen ; Uhlig, Till ; Hetland, Merete Lund ; Gudbjornsson, Bjorn

Objectives:

To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT).

Methods:

Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking.

Results:

In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks.

Conclusions:

Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice.

Trial registration number:

EudraCT 2011-004720-35; ClinicalTrials.govNCT01491815.

2024-11-01·RHEUMATOLOGY

Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis

Article

作者: Lauwerys, Bernard ; Mikuls, Ted R ; Ufuktepe, Baran ; Curtis, Jeffrey R ; Tilt, Nicola ; Xavier, Ricardo M ; Smolen, Josef S ; Taylor, Peter C ; Cara, Carlos ; Takeuchi, Tsutomu ; Tanaka, Yoshiya ; Hashimoto, Motomu ; Balsa, Alejandro ; Weinblatt, Michael

Abstract:

Objectives:

To assess the impact of baseline RF level on drug concentrations and efficacy of certolizumab pegol [CZP; TNF inhibitor (TNFi) without a crystallizable fragment (Fc)] and adalimumab (ADA; Fc-containing TNFi) in patients with RA.

Methods:

The phase 4 EXXELERATE study (NCT01500278) was a 104-week, randomized, single-blind (double-blind until week 12; investigator-blind thereafter), head-to-head study of CZP vs ADA in patients with RA. In this post hoc analysis, we report drug concentration and efficacy outcomes stratified by baseline RF quartile (≤Q3 or >Q3).

Results:

Baseline data by RF quartiles were available for 453 CZP-randomized and 454 ADA-randomized patients (≤Q3: ≤204 IU/ml; >Q3: >204 IU/ml). From week 12, the area under the curve (AUC) of ADA concentration was lower in patients with RF >204 IU/ml vs patients with RF ≤204 IU/ml; the AUC of CZP concentration was similar in patients with RF ≤204 IU/ml and >204 IU/ml. For patients with RF ≤204 IU/ml, disease activity score (DAS28)-CRP was similar between CZP- and ADA-treated patients through week 104. For patients with RF >204 IU/ml, mean DAS28-CRP was lower in CZP- vs ADA-treated patients at week 104. The proportion of patients with RF >204 IU/ml achieving DAS28-CRP low disease activity at week 104 was greater in CZP- vs ADA-treated patients.

Conclusion:

CZP was associated with maintained drug concentration and efficacy in patients with RA and high RF and may therefore be a more suitable therapeutic option than TNFis with an Fc fragment in these patients.

Trial registration:

Clinicaltrials.gov, http://clinicaltrials.gov, NCT01500278

2024-10-01·Dermatology and Therapy

Correction: Certolizumab Pegol for the Treatment of Plaque Psoriasis in Routine Clinical Practice: One-Year Results from the CIMREAL Study

作者: Fierens, Frederik ; Shimizu, Saori ; Sarro, David Vidal ; Lynde, Charles W ; Korge, Bernhard ; Lazaridou, Elisavet ; Perrussel, Marc ; Warren, Richard B ; Vanhooteghem, Olivier ; Lynde, Charles W. ; Machovcova, Alena ; Marasca, Claudio ; Williams, Paulette ; Warren, Richard B. ; Heidbrede, Tanja ; Pousa, Ines Duenas

项与培塞利珠单抗相关的新闻（医药）

2024-10-29

·PRNewswire

Genascence Appoints Jeymi Tambiah as Chief Medical Officer

—Accomplished physician-scientist with more than 15 years' biopharmaceutical industry experience in medical affairs, clinical development, and drug development —Visionary leader skilled at leveraging scientific and clinical expertise to build innovative first-in-class therapeutic programs in areas of osteoarthritis, immunology, oncology, and neuroscience PALO ALTO, Calif., Oct. 29, 2024 /PRNewswire/ -- Genascence Corporation ("Genascence"), a clinical-stage biotechnology company revolutionizing the treatment of prevalent musculoskeletal diseases with gene therapy, today announced the appointment of Jeymi Tambiah, MBChB, FRCS, MS, FAPCR, MFPM(Dis) as its chief medical officer. Dr. Tambiah is an accomplished physician-scientist with more than 15 years' biopharmaceutical industry experience creating and leading strategies for medical affairs, clinical development, and drug development programs. He also brings deep experience in translational medicine, commercialization, and health outcomes research to Genascence. Continue Reading Jeymi Tambiah, Chief Medical Officer, Genascence "Jeymi is a visionary leader skilled at leveraging scientific and clinical expertise to build innovative first-in-class therapeutic programs in the areas of osteoarthritis, immunology, oncology, and neuroscience and I am excited to welcome him to Genascence as our chief medical offer," said Thomas Chalberg, Ph.D., founder and CEO of Genascence. "His experience includes all phases of drug development from bench through Phase 1-4 clinical studies and building elite high performance medical affairs teams. Jeymi's development and research expertise, particularly within the osteoarthritis research community, will be invaluable as we execute on our strategy to bring gene therapy to people suffering from prevalent musculoskeletal diseases." "Genascence is a company that is transforming how we treat debilitating musculoskeletal diseases like osteoarthritis by pioneering the development of gene therapy," said Dr. Tambiah. "I am thrilled to join this outstanding team under Tom's leadership and apply my knowledge and experience to advance our clinical program so that we can bring potentially curative therapies to patients in desperate need of better treatments." Before joining Genascence, Jeymi was senior vice president of clinical development and external innovation at Biosplice Therapeutics, a start-up biotech developing molecules modulating mRNA splicing in oncology, arthritis, and neurodegenerative diseases, where he was primarily responsible for clinical development, medical affairs, and external thoughtleader and scientific partnerships. Previously, Jeymi worked for UCB Pharma in various roles of increasing leadership within medical affairs, launching the TNF-inhibitor certolizumab pegol within the European Union, U.K., and U.S. across multiple immunology indications. Before his move into pharma, Jeymi trained and practiced in cardiothoracic surgery at Guys' and St. Thomas' Hospitals in London. Jeymi is very active in the osteoarthritis research community, with numerous research awards and publications, holding many committee appointments, and regularly presenting at international conferences. He is the North American representative for the Faculty of Pharmaceutical Medicine UK, and in this role is dedicated to supporting the education and mentoring of physicians in drug development. Jeymi earned his medical degree from the University of Manchester, UK, a doctorate degree in vascular biology from Imperial College London where he was a Wellcome Research Fellow, and a BSc (Hons) in medical science from the University of St. Andrews, UK. He is a fellow of the Royal College of Surgeons of England and Edinburgh, a member of Faculty of Pharmaceutical Physicians UK by Distinction, and a fellow of the Academy of Physicians in Clinical Research. About Genascence Corporation Genascence, a clinical-stage biotechnology company revolutionizing the treatment of prevalent musculoskeletal diseases with gene therapy, is developing life-changing treatments for highly prevalent conditions affecting millions of people. The company was founded in 2017 with technology licensed from three leading U.S. research institutions: Mayo Clinic, University of Florida, and NYU Langone Health. Headquartered in Palo Alto, California, Genascence's founders and leadership team have deep experience in the design, development, and manufacturing of successful gene therapies and biological medicines. For more information, please visit . SOURCE Genascence WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

高管变更基因疗法

2024-10-22

·医药笔记

优时比：罗氏退回Tau抗体全球权益

▎Armstrong 2024年10月22日，优时比宣布Tau抗体Bepranemab治疗潜伏期至轻度阿尔茨海默症的2a期TOGETHER临床数据将在今年CTAD会议上报告，该会议的时间是10月29日至11月1日。同时，优时比宣布合作伙伴罗氏旗下基因泰克退回了Bepranemab的全球权益。 Bepranemab是一种重人源化的IgG4亚型的Tau抗体，可特异性靶向tau的中间区域（氨基酸235-250），靠近微管结合区（MTBR）。研究认为，与靶向tau其他区域（即N端）的抗体相比，中间区域抗体可以更有效地干扰致病性tau聚集体的细胞间传播。总结优时比在抗体领域布局了不少独具特色的产品，除了此次被退回的Tau抗体外，还有唯一一款PEG修饰的TNFα抗体Cimzia，也是其目前最畅销的创新药，年销售额20亿美元左右。Bimzelx为全球首款IL-17A/F抗体，今年上半年销售额2.15亿欧元，放量迅速。Rystiggo为一款FcRn抗体，今年上半年销售额7700万欧元，Zilbrysq为一款补体C5大环态抑制剂，今年4月上市，首季度销售额1500万欧元。 Armstrong技术全梳理系列 GPRC5D靶点全梳理； CD40靶点全梳理； CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向； Claudin 6靶点全梳理； Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇； CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理； Ambrx技术全梳理； Vir Biotech技术全梳理； Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；科望医药技术全梳理2.0；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理； Momenta技术全梳理； NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

临床2期抗体药物偶联物

2024-09-30

·凯莱英Asymchem

【关注】自身免疫疾病的药物开发与市场

来源：小药说药前言人类基因组的破译加上生物技术的进步，特别是单克隆抗体（mAbs）的里程碑式发现，使得生物治疗极大地改善了病人的生存时间和生存状态。目前，已经有超过300种生物疗法获得美国食品和药物管理局（FDA）批准，其中许多被批准用于治疗免疫和炎症性疾病。 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。治疗靶点与开发药物下表列出了经FDA批准用于自身免疫疾病适应症，以及处于关键3期临床试验或阳性的2期临床试验中的生物疗法。白细胞介素-1 IL-1α和IL-1β定位于对无菌状态下和微生物介导的炎症反应的迅速响应。当上皮细胞、内皮细胞和血小板对组织损伤作出反应时，IL-1α作为一种报警素发挥作用。相反，髓系来源的亚型IL-1β是作为一种非活性蛋白合成的，需要炎症小体驱动的蛋白水解过程才能发挥活性。IL-1α/β属于较大的IL-1细胞因子家族，它利用IL-1受体辅蛋白（IL-1RAcP）与IL-1R1亚基配对产生MyD88依赖性信号。IL-1α/β功能也受天然拮抗剂IL-1Ra、sIL-1RAcp和诱饵受体IL-1R2的调控。IL-1α/β表达失调与以发热、皮疹、关节炎和器官特异性炎症为特征的多种全身性自身炎症性疾病（SAID）有关。 FDA已经批准了三种不同性质的生物疗法，但都是针对IL-1的。Anakinra是一种天然拮抗剂IL-1Ra的改良版本，它同时抑制IL-1α和IL-1β。Anakinra被批准用于治疗RA和CAPS，其半衰期短，为5-6小时，因此需要每天皮下注射。Anakinra对痛风也有效，尿酸单钠晶体刺激NLRP3激活和IL-1β产生。Canakinumab是一种IL-1β中和抗体，每4-8周皮下给药一次，被批准用于治疗全身性青少年特发性关节炎（SJIA）和SAIDs。Rilonacept编码IL-1R和IL-1AcP的胞外结构域，与IgG的Fc部分相连，优先中和IL-1β，批准用于SAIDs的每周皮下给药。白细胞介素-6 IL-6是gp130细胞因子家族的一员，是许多稳态和炎症过程的中心组成部分。IL-6最初被鉴定为促进B细胞分化的T细胞衍生因子，现在因其在适应性免疫中的多效性活性而受到重视。它有助于Th17和T滤泡辅助细胞（Tfh）的分化，驱动髓样细胞分化，并与Th2细胞因子协同促进巨噬细胞极化为促纤维化表型。IL-6在肝脏急性期反应中起重要作用，增加包括C反应蛋白（CRP）在内的炎症蛋白，增强补体与病原体或死亡细胞的结合，对内皮细胞功能和上皮细胞完整性也有重要影响。 IL-6的广泛生物活性源于其调节多个细胞靶点的复杂性质。IL-6由多种细胞合成，并通过三种不同的细胞表面信号机制（即经典信号、反式信号和反式呈递）激活靶细胞，最终产生JAK/STAT信号。 Tocilizumab和sarilumab是FDA批准的两种IL-6R阻断性单抗，许多其他药物正在临床开发中。Tocilizumab和sarilumab被FDA批准用于治疗中重度RA，其中受影响关节滑液中IL-6水平升高，血清IL-6水平与疾病活动相关。这两种药物都能改善RA患者的炎症症状并减少影像学进展。细胞因子释放综合征（CRS）是一种急性全身炎症性疾病，与许多基于抗体的治疗、化疗和T细胞参与的免疫治疗（如CAR-T细胞）以及严重感染相关。与T细胞参与疗法相关的CRS被认为是由活化的T细胞产生TNF-α，进而触发单核细胞和活化的巨噬细胞产生IL-6和IL-1β。CRS症状（例如发烧和低血压）的缓解通常在单剂量的Tocilizumab后实现。给药tocilizumab似乎并不影响T细胞参与疗法的抗肿瘤效果。肿瘤坏死因子 TNF-α主要由免疫细胞和内皮细胞产生，并通过促炎信号和细菌产物显著上调；TNF-β(LTα)主要由淋巴细胞产生。TNF-α以三聚体膜结合形式（mTNF）表达并经历蛋白水解裂解产生可溶性三聚体sTNF。TNFR1广泛表达，而TNFR2主要表达于神经元、免疫细胞和内皮细胞。TNF-α具有多效性功能。TNF-α对病原体的最佳防御、淋巴器官的正常发育以及在神经元再髓鞘化、心脏重塑和软骨再生中的重要修复作用都是必需的。目前有五种TNF抑制剂被FDA批准用于临床，全部都靶向TNF-α，其中依那西普另外抑制TNF-β。肿瘤坏死因子拮抗剂的分子类型反映了近二十年来生物治疗药物的发展。依那西普（TNFR2-Fc）是FDA批准的第一个Fc融合蛋白；infliximab是第一代嵌合单抗；adalimumab是来源于噬菌体展示的人源单抗；golimumab是来源于表达人IgG的转基因小鼠的人源单抗；certolizumab-pegol是一种从小鼠杂交瘤中分离的人源化Fab片段，经聚乙二醇化可延长其体内半衰期。大多数肿瘤坏死因子拮抗剂显示出共同的临床疗效。然而，依那西普在克罗恩病（CD）的随机双盲安慰剂对照试验中无效，可能反映了TNF抑制剂治疗机制的差异。除了中和sTNF-α外，抗TNF抗体和certolizumab-pegol(而不是依那西普)可通过结合mTNF或阻断抗凋亡信号诱导固有层T细胞凋亡。此外，抗TNF单抗（而非依那西普或certolizumab-pegol）可通过Fc依赖机制诱导M2型创伤愈合巨噬细胞应答。因此，TNF拮抗剂之间的机制差异可能是导致其在CD中不同临床效果的原因。 CD20 CD20是一种B细胞标志物，其表达始于早期的前B细胞，但在向浆细胞的终末分化过程中丢失。它是一种四肽蛋白，是B细胞发挥最佳功能和免疫反应所必需的。 Rituximab是一种嵌合单抗，是FDA批准的第一种治疗B细胞非霍奇金淋巴瘤的抗CD20单抗。基于其在肿瘤学中令人惊讶的良好安全性，研究人员开始探索其在严重自身免疫性疾病患者中的应用。Rituximab目前被FDA批准用于治疗多种自身免疫性疾病。由于CD20既不在HSC上表达，也不在终末分化的浆细胞上表达，因此抗CD20单抗选择性靶向CD20+B细胞与先天性B细胞缺乏具有不同的免疫学后果。例如，用抗CD20抗体治疗后，血清IgG水平没有显著影响，而严重的X连锁无丙种球蛋白血症（其中B细胞不发育）则观察到缺乏免疫球蛋白。最近的一项2期研究使用了obinutuzumab，一种具有增强ADCC和诱导B细胞凋亡能力的II型抗CD20单抗，已报道狼疮性肾炎患者的临床获益（NCT 02550652）。需要对obinutuzumab进行进一步的研究，以确认额外的B细胞消耗是否对狼疮性肾炎有益。 BAFF/APRIL肿瘤坏死因子超家族成员 BAFF和APRIL是TNF配体超家族的两种II型跨膜蛋白，它们的受体BAFFR、BCMA和TACI在B系细胞的存活和成熟以及功能中起着重要作用。血清BAFF和APRIL水平在许多自身免疫性疾病中升高，包括SLE、Sjögren综合征和RA。Belimumab是一种人IgG1λ单抗，被批准用于治疗活动性自身抗体阳性的SLE。它抑制sBAFF三聚体，但不与mBAFF或APRIL结合。在关键的临床试验中，与SOC组相比，belimumab在SLE应答指数和健康相关生活质量终点方面有更大的改善。此外，belimumab降低了循环中原始B细胞、活化B细胞和浆细胞的数量；抗dsDNA水平降低，补体水平正常化。与对循环记忆B和T细胞缺乏影响一致，治疗一年后，先前存在的抗肺炎、破伤风和甲型流感抗体没有受到影响。 Atacicept是融合TACI胞外区的Fc融合蛋白，结合BAFF、APRIL和BAFF/APRIL异源聚体。在系统性红斑狼疮患者中应用Atacicept治疗后，血清IgM（∼70%）、IgG（∼30–40%）和IgA（∼50–60%）迅速下降，抗双链DNA抗体下降了∼40%。终止治疗后，抗体和自身抗体水平恢复到预处理水平。整合素家族整合素通过调节白细胞与血管的粘附来调节免疫细胞的运输，并促进白细胞向组织中的外渗。整合素异二聚体由18个α亚单位和8个β亚单位之间的配对组成，形成24种不同的受体复合物，它们在表达模式、配体特异性和功能上存在差异。在MS中，α4β1（CD49d/CD29，VLA4）在T和B细胞上表达，并通过VCAM1与血脑屏障内皮细胞的结合促进淋巴细胞向中枢神经系统（CNS）的外渗。在胃肠道中，表达于T细胞上的α4β7可与Peyer氏斑高内皮小静脉和固有层小静脉上的MADCAM-1结合，促进炎症性肠病（IBD）致病性T细胞的外渗。 Natalizumab是一种α4阻断性单抗，被批准用于治疗CD和RMS患者。然而，RMS抑制淋巴细胞进入中枢神经系统的有效性的机制基础也为进展性多灶性白质脑病（PML）的罕见病例的发展提供了基础。第二代抗体，包括vedolizumab（对α4β7复合物有选择性）和etrolizumab（抗β7），通过针对IBD的肠道特异性整合素降低PML的可能性。Vedolizumab可诱导临床反应和缓解，FDA已批准用于溃疡性结肠炎（UC）和CD。除了阻断α4β7:MADCAM1相互作用外，etrolizumab还干扰E-钙粘蛋白+肠上皮细胞对αEβ7+IELs的保留。在一项2期临床试验中，与对照组相比，对UC患者使用etrolizumab治疗导致临床病情缓解的可能性更大。由于αEβ7+IELs是UC患者炎症细胞因子的重要贡献者，因此阻断α4β7和αEβ7整合素可能有额外的临床益处。抗αL抗体Efalizumab阻断T细胞和B细胞表达的αLβ2（LFA1）与ICAM1的相互作用。除了阻断整合素外，Efalizumab还下调LFA-1的表达，LFA-1是T细胞与抗原呈递细胞（APC）形成突触所必需的。Efalizumab被FDA批准用于治疗中度至重度斑块型银屑病。然而，4名使用Efalizumab治疗3年以上的患者出现了PML，该药物已退出市场。白细胞介素-12和-23及其下游效应物 IL-12和IL-23是两种密切相关的APC衍生的异二聚体细胞因子，分别由p35和p19亚单位组成，它们与一个共同的p40亚单位配对。这两种细胞因子，主要的应答细胞是T细胞和固有淋巴细胞（ILCs），在不同的细胞类型中，IL-12上调Th1主转录因子T-bet的表达并诱导IFN-γ的产生。以类似的方式，IL-23刺激诱导转录因子RORγt的表达和下游细胞因子IL-17A、IL-17F、IL-22和GM-CSF的表达。疾病的临床前模型和全基因组关联研究表明IL-12/23通路参与炎症性肠病和银屑病。设计用于干扰IL-12/23通路各种成分的多种疗法已进入临床。两种单抗（ustekinumab和briakinumab）靶向p40亚单位，从而中和IL-12和IL-23。最近，效应细胞因子的IL-17家族引起了广泛关注，有5种单抗选择性中和IL-17A；2种单抗中和IL-17A和F；brodalumab靶向IL-17RA，一种IL-17A、B、C、E和F成员的共同受体。然而，虽然IL-17B-E的不同功能已被描述，但这些细胞因子不受IL-23的调节，它们在人类疾病中的作用仍未被充分研究。此外，对阻断IL-22（fezakinumab）、IFN-γ（fontolizumab）和GM-CSF（namilumab和mavrilimumab）治疗的研究将提供进一步的见解，尽管它们还处于早期研究。自免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。参考文献： 1.30 Years of Biotherapeutics Development-What Have We Learned? Annu Rev Immunol. 2020 Apr 26;38:249-287 2. 弗若斯特沙利文报告

临床3期上市批准临床2期免疫疗法

100 项与培塞利珠单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03441	培塞利珠单抗	L04AB05	DB08904

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
红皮病性银屑病	日本	UCB Japan Co. Ltd.	2019-12-20
寻常性银屑病	日本	UCB Japan Co. Ltd.	2019-12-20
脓疱型银屑病	日本	UCB Japan Co. Ltd.	2019-12-20
非放射性轴性脊柱关节炎	美国	UCB, Inc.	2019-03-28
斑块状银屑病	美国	UCB, Inc.	2013-10-17
强直性脊柱炎	欧盟	UCB Pharma Ltd.	2009-10-01
强直性脊柱炎	冰岛	UCB Pharma Ltd.	2009-10-01
强直性脊柱炎	列支敦士登	UCB Pharma Ltd.	2009-10-01
强直性脊柱炎	挪威	UCB Pharma Ltd.	2009-10-01
银屑病关节炎	欧盟	UCB Pharma Ltd.	2009-10-01
银屑病关节炎	冰岛	UCB Pharma Ltd.	2009-10-01
银屑病关节炎	列支敦士登	UCB Pharma Ltd.	2009-10-01
银屑病关节炎	挪威	UCB Pharma Ltd.	2009-10-01
中轴性脊柱关节炎	欧盟	UCB Pharma Ltd.	2009-10-01
中轴性脊柱关节炎	冰岛	UCB Pharma Ltd.	2009-10-01
中轴性脊柱关节炎	列支敦士登	UCB Pharma Ltd.	2009-10-01
中轴性脊柱关节炎	挪威	UCB Pharma Ltd.	2009-10-01
类风湿关节炎	美国	UCB, Inc.	2009-05-13
克罗恩病	美国	UCB, Inc.	2008-04-22

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
银屑病	临床3期	比利时	UCB SA	2022-01-30
慢性大斑块银屑病	临床3期	美国	UCB Biopharma SRL	2020-01-21
慢性大斑块银屑病	临床3期	加拿大	UCB Biopharma SRL	2020-01-21
慢性大斑块银屑病	临床3期	波多黎各	UCB Biopharma SRL	2020-01-21
泛发性脓疱型银屑病	临床3期	日本	UCB Biopharma SRL	2017-02-21
间质性膀胱炎	临床3期	美国	UCB Pharma GmbH	2015-12-15
炎症	临床3期	美国	UCB BioSciences GmbH	2015-09-01
炎症	临床3期	澳大利亚	UCB BioSciences GmbH	2015-09-01
炎症	临床3期	保加利亚	UCB BioSciences GmbH	2015-09-01
炎症	临床3期	加拿大	UCB BioSciences GmbH	2015-09-01

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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


NCT04163016 (CHERISH, CTgov)	临床1期	斑块状银屑病 \| 银屑病关节炎 \| 炎症 ... 更多	22	CZP (CZP 200 mg Q2W)	顧積範淵夢構齋願夢鹹(鬱選範憲繭獵膚蓋衊壓) = 製艱簾夢築鑰衊範壓鬱餘簾艱艱鹹壓齋餘鏇鹹 (齋鹽築繭醖壓繭積鬱製, 鏇糧鑰蓋鹹鬱壓廠膚憲 ~ 築鑰膚製餘製範襯構廠) 更多	-	2024-09-19
				CZP (CZP 400 mg Q2W)	範淵構鹽願製衊窪衊膚(鹹選鏇淵糧膚鹹遞壓夢) = 獵齋顧獵願餘糧餘艱製獵觸鬱製鏇蓋選獵顧遞 (觸繭獵餘醖網鬱齋網壓, 構鹽鏇構製遞鏇願鹽蓋 ~ 觸願窪膚製築鑰獵壓鹽) 更多
NCT04053881 (CIMREAL, Pubmed)	N/A	斑块状银屑病 tumor necrosis factor alpha (TNFα)	399	Certolizumab pegol 400 mg	餘構構範願憲衊廠鏇衊(餘願鏇鹹蓋鹹齋觸窪顧) = 夢構襯糧夢夢鬱願繭願廠鬱醖蓋顧艱積襯鹹膚 (簾顧齋蓋膚鑰糧鏇醖製 ) 更多	积极	2024-06-27
				Certolizumab pegol 200 mg	餘構構範願憲衊廠鏇衊(餘願鏇鹹蓋鹹齋觸窪顧) = 壓顧鹹鑰積繭簾觸夢鏇廠鬱醖蓋顧艱積襯鹹膚 (簾顧齋蓋膚鑰糧鏇醖製 ) 更多
NCT04163016 (CHERISH, EULAR2024) 人工标引	临床1期	自身免疫性疾病	21	CERTOLIZUMAB PEGOL	遞壓鏇齋窪鏇膚膚選鏇(衊製夢鑰襯範齋觸膚淵) = 鏇壓憲衊艱鹹糧壓鏇壓簾壓壓觸憲鹹膚壓齋觸 (顧構淵願蓋簾簾網顧齋 )	积极	2024-06-14
EULAR2024	N/A	中轴性脊柱关节炎	-	Certolizumab	餘糧鹹製選艱鏇蓋鹹鏇(壓鹹糧積積獵網製鑰範) = 繭醖餘糧網遞齋範膚範鏇鏇壓窪淵膚衊窪窪製 (鏇積衊齋築願繭簾窪鬱 )	积极	2024-06-05
				Secukinumab	餘糧鹹製選艱鏇蓋鹹鏇(壓鹹糧積積獵網製鑰範) = 衊夢製遞願遞鹽艱範繭鏇鏇壓窪淵膚衊窪窪製 (鏇積衊齋築願繭簾窪鬱 )
Apulian BIOPURE registry (EULAR2024)	N/A	慢性关节炎	542	Certolizumab (Fertile female patients)	獵餘鏇選獵範遞選簾築(艱顧襯鑰鑰鏇遞蓋鑰壓) = 製艱築壓壓選築製膚鏇憲觸夢齋觸艱鏇夢積襯 (廠鏇顧構糧觸廠顧艱膚 ) 更多	积极	2024-06-05
				Certolizumab (Menopausal female patients)	獵餘鏇選獵範遞選簾築(艱顧襯鑰鑰鏇遞蓋鑰壓) = 糧構鏇願製廠鹽壓鬱夢憲觸夢齋觸艱鏇夢積襯 (廠鏇顧構糧觸廠顧艱膚 ) 更多
NCT01500278 (EXXELERATE, ACR2023) 人工标引	临床4期	类风湿关节炎	907	Certolizumab Pegol+Methotrexate	鏇網壓糧繭願選築壓膚(糧鑰繭鹽醖鏇範蓋繭繭) = 鏇膚願鹹蓋遞願構膚顧顧觸廠艱夢遞繭鹹築選 (淵衊廠廠淵鹽鬱餘窪壓 ) 更多	非优	2023-11-14
				Adalimumab+Methotrexate	鏇網壓糧繭願選築壓膚(糧鑰繭鹽醖鏇範蓋繭繭) = 蓋鬱獵鬱觸醖鑰襯顧範顧觸廠艱夢遞繭鹹築選 (淵衊廠廠淵鹽鬱餘窪壓 ) 更多
ACR2023	N/A	Rheumatoid Factor (RF)	755	Certolizumab Pegol	壓糧選襯觸醖製衊獵鹽(鹽鑰願網衊網積築襯窪) = 襯鑰鬱範遞壓觸製鑰鏇鑰願願觸夢構齋構築憲 (廠鏇糧夢觸觸淵醖鑰繭, 3.7 ~ NA)	积极	2023-11-13
				Monoclonal Antibodies (mAB)	壓糧選襯觸醖製衊獵鹽(鹽鑰願網衊網積築襯窪) = 窪鏇鏇醖鹽網襯顧膚網鑰願願觸夢構齋構築憲 (廠鏇糧夢觸觸淵醖鑰繭, 3.3 ~ 8.7)
NCT04740814 (CTgov)	临床1期	类风湿关节炎	33	Certolizumab Pegol	顧壓願膚窪齋鹽齋鹽齋(構範鬱願顧築築觸齋醖) = 獵製範簾鹹遞鬱鬱網壓顧齋繭憲醖製遞齋淵壓 (獵憲艱膚積廠遞齋獵鹽, 膚鹹淵齋憲觸製淵獵壓 ~ 鑰淵顧鏇鏇窪獵遞遞遞) 更多	-	2023-11-13
NCT04053881 (CIMREAL, EADV2023)	N/A	银屑病	399	Certolizumab pegol	艱願淵壓鑰窪淵淵鬱蓋(齋壓衊夢獵壓艱範鬱簾) = 選窪壓獵襯築觸選夢願鬱築鏇範廠蓋憲膚顧顧 (鹹構鏇糧壓餘廠築築壓 ) 更多	积极	2023-10-11
NCT04053881 (CIMREAL, EADV2023)	N/A	斑块状银屑病	399	Certolizumab pegol 400 mg Q2W	壓鹽願範遞壓繭壓齋醖(製網選選淵築鑰構壓膚) = 窪艱鑰醖築衊選艱餘憲醖廠鏇餘鑰夢顧餘醖糧 (鏇繭鏇鑰簾鑰積蓋窪範 ) 更多	积极	2023-10-11