Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States and other industrialized societies, and advanced age is the major risk factor for development of CVD. Advancing age appears to exert its pathological influence primarily via adverse functional and structural effects on arteries. Aging is associated with increased stiffness (reduced compliance) of large elastic arteries and impaired arterial endothelial function that is characterized by reductions in nitric oxide (NO)- mediated endothelium-dependent dilation (EDD). While several changes to arteries may contribute to age-associated increases in CVD risk; the development of endothelial dysfunction and stiffening of the large elastic arteries are among the most important contributors. Both are predictors of CV events and clinical CVD with increasing age. Although the importance of endothelial dysfunction and arterial stiffening with age are well established, the initiating events of these deleterious changes are elusive.

开始日期2024-11-01

申办/合作机构

University of Utah

[+1]

NCT06418529 / Active, not recruitingN/A

Comparative Effectiveness of New Initiators of Tofacitinib and Other Biologic/Targeted Synthetic DMARDs in Patients With Rheumatoid Arthritis

The purpose of this study is to learn how different types of medicines may improve disease activity in people with rheumatoid arthritis (RA). RA is a kind of joint disease that causes pain and swelling.
The study will look at data from a large, US-based group of RA patients who have taken the below medicines:
* Tofacitinib
* Abatacept
* Tocilizumab or sarilumab
The study will compare clinical disease activity scores of patients on the different medicines taken. The study will also decide whether some patient traits or disease factors play a role in how medicines may improve disease activity.

开始日期2024-05-15

申办/合作机构

Pfizer Inc.

NCT06395038 / Recruiting临床1期

A Phase I Clinical Trial, Using Interleukin-2 (IL-2) and Abatacept in Patients With Frontotemporal Disorders

Neuroinflammation is a significant component of Frontotemporal Disorder (FTD). Our preliminary unpublished data demonstrated that regulatory T cells (Tregs) have a compromised phenotype and reduced suppressive function in FTD patients, skewing the immune system toward a proinflammatory status and potentially contributing to disease progression. Low dose interleukin-2 (IL-2) is now viewed as a very promising immunoregulatory drug with the capacity to selectively expand and restore functional Tregs. Our preclinical data also demonstrated synergistic effect of interleukin-2 and abatacept (CTLA4-IgG) in remodeling immunologic pathways. Abatacept is an FDA approved medication that has been indicated as a monotherapy or concomitantly with other anti-inflammatory drugs to modulate inflammation in autoimmune disorders. This study is a phase I, open-label study to assess safety and tolerability of low dose IL-2 plus abatacept immunotherapy in FTD individuals. In the first part of this study, 5 FTD patients will be recruited. These five individuals will receive subcutaneous abatacept (125 mg) followed by five-day-courses of IL-2 (1MUI/day) every four weeks for a total of 21 weeks (part-1 of the study). If the treatment strategy is safe and well-tolerated, up to 5 additional FTD subjects will be recruited to receive subcutaneous abatacept (125 mg) followed by five-day-courses of IL-2 (1MUI/day) every two weeks for a total of 21 weeks (part 2 of the study).

开始日期2024-05-06

申办/合作机构

The Methodist Hospital Research Institute

100 项与阿巴西普相关的临床结果

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100 项与阿巴西普相关的转化医学

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100 项与阿巴西普相关的专利（医药）

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3,027

项与阿巴西普相关的文献（医药）

2024-12-01·Journal of Translational Autoimmunity

To switch or to swap? Evidence from a meta-analysis for the best treatment approach in childhood chronic uveitis resistant to the I anti-TNF

Review

作者: Pagnini, Ilaria ; Soldovieri, Sara ; Marrani, Edoardo ; Oliverio, Teodoro ; de Masi, Salvatore ; Maccora, Ilaria ; Simonini, Gabriele ; Mastrolia, Maria Vincenza

Objective:

Since adalimumab approval in childhood chronic non-infectious uveitis (cNIU), the prognosis has been dramatically changed, but the 25 % failed to achieve inactivity. There is not accordance if it is better to switch to another anti-TNF or to swap to another category of biologic. Thus, we aim to summarize evidence regarding the best treatment of cNIU refractory to the first anti-TNF.

Methods:

A systematic literature review and meta-analysis, according to PRISMA Guidelines, was performed(Jan2000-Aug2023). Studies investigating the efficacy of treatment in cNIU refractory to the first anti-TNF were considered for inclusion. The primary outcome was the improvement of intraocular inflammation according to SUN. A combined estimation of the proportion of children responding to switch or swap and for each drug was performed.

Results:

23 articles were eligible, reporting 150 children of whom 109 switched anti-TNF (45 adalimumab, 49 infliximab, 9 golimumab) and 41 swapped to another biologics (31 abatacept, 8 tocilizumab and 1 rituximab). The proportion of responding children was 46 %(95 % CI 23-70) for switch and 38 %(95 % CI 8-73) for swap (χ²0.02, p = 0.86). Instead analysing for each drug, the proportion of responding children was the 24 %(95 % CI 2-55) for adalimumab, 43 %(95 % CI 2-80) for abatacept, 79 %(95 % CI 61-93) for infliximab, 56 %(95 % CI 14-95) for golimumab and 96 %(95 % CI 58-100) for tocilizumab. We evaluated a superiority of tocilizumab and infliximab compared to the other drugs(χ² 27.5 p < 0.0001).

Conclusion:

Although non-conclusive, this meta-analysis suggests that, after the first anti-TNF failure, tocilizumab and infliximab are the best available treatment for the management of cNIU.

2024-12-01·TRANSPLANT IMMUNOLOGY

Smooth muscle cells clonally expand in a murine carotid allograft model complicated by immune reactions to reporter transgenes

Article

作者: Bentzon, Jacob Fog ; Sørensen, Charlotte Brandt ; Pløen, Gro Grunnet

BACKGROUND AND AIMS:

Most experimental studies of allograft vasculopathy (AV) have relied on transplantation between major histocompatibility complex-mismatched inbred mouse strains, but this leads to the complete eradication of donor smooth muscle cells (SMCs) and lesions formed by recipient cells. This is unlike human AV which is thought to form mainly by donor SMCs. Here, we studied sources of neointimal cells in a minor histocompatibility antigen-mismatched AV model by combining male-to-female orthotopic carotid transplantations and lineage tracing by SMC-specific expression of fluorescent proteins.

METHODS:

To track SMC-derived cells in allograft vasculopathy, we used male donor mice with SMC-restricted Cre recombination of the mT/mG reporter transgene, which switches expression of membrane-bound red fluorescent protein (RFP) to green fluorescent protein (GFP), or the stochastically recombining Confetti reporter transgene, which yields a mosaic expression of four fluorescent proteins. Donor carotid segments were harvested and orthotopically allografted to female recipients that were wildtype or had non-recombined reporter transgenes. Inhibition of T cell responses by CTLA4Ig was used in some experiments. Sections of lesions harvested after 4 weeks were analyzed by fluorescence microscopy.

RESULTS:

Donor-derived SMCs survived and gave rise to part of the neointimal cells in experiments where carotid segments from recombined mT/mG male mice were transplanted into wild-type or non-recombined mT/mG female mice. Sex-mismatched transplants developed significant lesions, increasing the intimal and medial area 4.6-fold (p = 0.038) and 2.0-fold (p = 0.024) compared to sex- and fluorescence-matched controls, respectively. Interestingly, sex-matched fluorescence-positive transplants developed intimal lesions in 50% of fluorescence-naïve recipient controls. To study the clonal structure of the neointimal donor-derived SMC lineage cells, we then transplanted male carotids with heterozygous or homozygous recombined Confetti transgenes into female recipients. These transplants developed lesions with few surviving donor SMCs, indicating that expression of the Confetti reporter increased rejection and donor-specific SMC death. Some of the few remaining donor SMCs underwent clonal expansion. CTLA4Ig administration at the time of surgery did not improve SMC survival in mT/mG or Confetti transplants.

CONCLUSION:

Male-to-female transplant models feature donor-derived SMCs, some of which undergo clonal expansion, but immune rejection to fluorescence reporters appears to bias results in lineage tracing models. Overcoming these challenges with alternative reporter transgenes or tolerant recipients is necessary to study the mechanisms by which donor SMCs contribute to allograft vasculopathy.

2024-12-01·TRANSPLANT IMMUNOLOGY

Regulation of cardiac allograft immune responses by microRNA-155

Article

作者: Bremner, Ross M. ; Guerrero-Alba, Alexa ; Smith, Michael A ; Mohanakumar, T ; Itabashi, Yoshihiro ; Mohanakumar, T. ; Bremner, Ross M ; Bansal, Sandhya ; Smith, Michael A. ; Fleming, Timothy

INTRODUCTION:

A better understanding of the immune mechanisms involved in allograft rejection after transplantation is urgently needed to improve patient outcomes. As microRNA-155 (miR155) plays a critical role in inflammation, we postulated that a deficiency of miR155 will improve cardiac allograft survival and enhance tolerance induction after heart transplantation.

METHODS:

We developed an acute rejection mouse model through heterotopic BALB/c cardiac transplantation to C57BL/6 (wild-type) and C57BL/6 miR155 knock-out (miR155KO) mice. Further, we induced tolerance in both groups through a costimulatory blockade with CTLA4-Ig (200 μg; post-transplant day 2) and MRI antibodies (250 μg; post-transplant day 0), targeting CD28/B7 and CD40/CD154 signals, respectively. Finally, we examined the effects of injecting 100 μg of small extracellular vesicles (sEVs) isolated from wild-type mice undergoing rejection into tolerant miR155KO mice.

RESULTS:

Mean survival time (MST) of the cardiac allografts in wild-type and miR155KO mice was 7 and 15 days, respectively (p < 0.0001). Costimulatory blockade increased MST to 65 days and > 100 days in the wild-type and miR155KO recipients, respectively (p < 0.001). Injection of sEVs isolated from wild-type mice undergoing rejection into tolerant miR155KO mice decreased the allograft survival to 9 days, significantly lower than the tolerant miR155KO mice without injection of sEVs (>100 days; p < 0.0001).

CONCLUSION:

miR155KO mice have improved cardiac allograft survival and enhanced induction of tolerance after heterotopic cardiac transplantation. Injection of sEVs from wild-type mice undergoing rejection into the miR155KO mice reversed these benefits.

164

项与阿巴西普相关的新闻（医药）

2024-09-24

·Business Wire

Coya Therapeutics to Participate in Fireside Chat at the Chardan 8th Annual Genetic Medicines Conference

HOUSTON--( BUSINESS WIRE )-- Coya Therapeutics, Inc. (NASDAQ: COYA) (“Coya” or the “Company”), a clinical-stage biotechnology company developing biologics intended to enhance regulatory T cell (Treg) function, announces that CEO Howard Berman, Ph.D. and Chief Business Officer and incoming Chief Executive Officer Arun Swaminathan, Ph.D, will participate in a fireside chat at the Chardan 8 th Annual Genetic Medicines Conference on Tuesday, October 1, 2024 at 2:00pm ET. The fireside chat will be moderated by Keay Nakae, Senior Research Analyst at Chardan Capital Markets. The conference is being held on September 30 – October 1, 2024 at the Westin Grand Central in New York City. Drs. Berman and Swaminathan will be available for one-on-one meetings throughout the conference. About Coya Therapeutics, Inc. Headquartered in Houston, TX, Coya Therapeutics, Inc. (Nasdaq: COYA) is a clinical-stage biotechnology company developing proprietary treatments focused on the biology and potential therapeutic advantages of regulatory T cells (“Tregs”) to target systemic inflammation and neuroinflammation. Dysfunctional Tregs underlie numerous conditions, including neurodegenerative, metabolic, and autoimmune diseases, and this cellular dysfunction may lead to sustained inflammation and oxidative stress resulting in lack of homeostasis of the immune system. Coya’s investigational product candidate pipeline leverages multiple therapeutic modalities aimed at restoring the anti-inflammatory and immunomodulatory functions of Tregs. Coya’s therapeutic platforms include Treg-enhancing biologics, Treg-derived exosomes, and autologous Treg cell therapy. COYA 302 – the Company’s lead biologic investigational product or “Pipeline in a Product” – is a proprietary combination of COYA 301 (Coya’s proprietary LD IL-2) and CTLA4-Ig for subcutaneous administration with a unique dual mechanism of action that is now being developed for the treatment of Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson’s Disease, and Alzheimer’s Disease. Its multi-targeted approach enhances the number and anti-inflammatory function of Tregs and simultaneously lowers the expression of activated microglia and the secretion of pro-inflammatory mediators. This synergistic mechanism may lead to the re-establishment of immune balance and amelioration of inflammation in a sustained and durable manner that may not be achieved by either low-dose IL-2 or CTLA4-Ig alone. For more information about Coya, please visit www.coyatherapeutics.com Forward-Looking Statements This press release contains “forward-looking” statements that are based on our management’s beliefs and assumptions and on information currently available to management. Forward-looking statements include all statements other than statements of historical fact contained in this presentation, including information concerning our current and future financial performance, business plans and objectives, current and future clinical and preclinical development activities, timing and success of our ongoing and planned clinical trials and related data, the timing of announcements, updates and results of our clinical trials and related data, our ability to obtain and maintain regulatory approval, the potential therapeutic benefits and economic value of our product candidates, competitive position, industry environment and potential market opportunities. The words “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” and similar expressions are intended to identify forward-looking statements. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors including, but not limited to, those related to risks associated with the impact of COVID-19; the success, cost and timing of our product candidate development activities and ongoing and planned clinical trials; our plans to develop and commercialize targeted therapeutics; the progress of patient enrollment and dosing in our preclinical or clinical trials; the ability of our product candidates to achieve applicable endpoints in the clinical trials; the safety profile of our product candidates; the potential for data from our clinical trials to support a marketing application, as well as the timing of these events; our ability to obtain funding for our operations; development and commercialization of our product candidates; the timing of and our ability to obtain and maintain regulatory approvals; the rate and degree of market acceptance and clinical utility of our product candidates; the size and growth potential of the markets for our product candidates, and our ability to serve those markets; our commercialization, marketing and manufacturing capabilities and strategy; future agreements with third parties in connection with the commercialization of our product candidates; our expectations regarding our ability to obtain and maintain intellectual property protection; our dependence on third party manufacturers; the success of competing therapies or products that are or may become available; our ability to attract and retain key scientific or management personnel; our ability to identify additional product candidates with significant commercial potential consistent with our commercial objectives; ; and our estimates regarding expenses, future revenue, capital requirements and needs for additional financing. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy, short-term and long-term business operations and objectives, and financial needs. Moreover, we operate in a very competitive and rapidly changing environment, and new risks may emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed herein may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Although our management believes that the expectations reflected in our forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances described in the forward-looking statements will be achieved or occur. We undertake no obligation to publicly update any forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

细胞疗法免疫疗法

2024-09-17

·药渡

单季度突破10亿美金的免疫治疗大分子

最近两年，自身免疫疾病药物的开发炙手可热，而其背后真正的原因还是要归咎于自免足够大的市场，根据沙利文报告显示，全球各类自免疾病患者规模近5亿人，2022年该领域药物市场规模约达1323亿美元，预计到2030年将达到1760亿美元。而且在该领域，爆款药品不断出现，先是Humira，后有Dupixent。随着2024年第二季度的财报披露，该领域单季度销售超过10亿美金的药物也先后出现，根据统计，该领域目前有10款药物单季度销售额超过或者接近10亿，其中9款是大分子，一款小分子。艾伯维占据3款，强生两款，诺华两款。 1 Dupixent (IL4/IL13 mAb) Dupixent是由赛诺菲和再生元联合开发的靶向白细胞介素-4（IL-4）和白细胞介素-13（IL-13）共享的受体亚基α（IL-4Rα）的单克隆抗体，自2017年3月28日获得美国FDA批准上市以来，Dupixent已经在全球多个国家获批用于治疗：1）中至重度特应性皮炎（AD）：适用于6个月及以上的患者，尤其是当外用药物无法有效控制症状或不适用时；2)中度至重度结节性痒疹（PN）：适用于成人患者，特别是那些需要系统治疗的情况;3)哮喘：适用于12岁及以上的青少年和成人，特别是那些使用中到高剂量吸入性糖皮质激素（ICS）和其他哮喘控制药物后仍然控制不佳的患者，以及那些依赖口服糖皮质激素的哮喘患者。 Dupixent2023年的销售额到达115.7亿美元，而且2024年预计将达到130亿欧元（约合140亿美元），根据赛诺菲第二季度的财报公布，Dupixent 2024Q2的销售额为33亿欧元，与2023三年同期相比，增加了29%，而对于前两个季度的销售，2024的已经达到了61亿欧元，与去年同期相比增加了约26%。从目前的销售额来看，Dupixent很有可能到达130亿欧元。除了已经获批的适应症，COPD适应症在今年已经在欧盟获批，而且预计今年9月份也将会在US会批，这是十多年来欧盟首个针对COPD批准的新治疗方法，也是首个针对COPD患者获批的靶向治疗药物。根据Frost & Sullivan 统计，2019 年全球COPD 患者基数约4.57亿人，预计2024 年约5.28亿人，2019-2024 CAGR 约3.0%；2019 年国内COPD 患者数量约1.04亿人，预计2024 年患者基数约1.08 亿人。关于其它适应症，青少年鼻息肉慢性鼻窦炎已经在美国申报；儿童嗜酸性粒细胞性食管炎适应症已经在欧盟申报；大疱性类天疱疮和慢性自发性荨麻疹已经位于临床三期。 2 Stelara（ustekinumab/喜达诺） Stelara（通用名：ustekinumab，中文商品名：喜达诺）是一种由强生公司（JNJ）旗下的杨森制药开发并生产的生物制剂，用于治疗多种免疫介导的炎症性疾病。它是一种选择性靶向IL-12和IL-23的生物制剂，通过与这两种细胞因子共有的p40亚基结合，阻止它们与细胞表面受体IL-12 β1结合，从而抑制炎症反应。2009年9月上市以来Stelara已经获批用于治疗以下疾病：1）中度至重度斑块型银屑病（PsO）的儿科患者（6-11岁）和青少年及成人患者（≥12岁）；2）成人活动性银屑病关节炎；3）成人中重度克罗恩病（CD）；4）成人中重度活动性溃疡性结肠炎（UC）。 Stelara的给药方式是通过皮下注射，起始剂量后，通常每年给药4次。在中国，Stelara（喜达诺®）于2019年6月上市，用于治疗对其他系统治疗不应答、有禁忌或无法耐受的成年中重度斑块状银屑病患者。根据强生Q2财报披露，Stelara第二季度销售额为28.9亿美元，但是其美国专利已于2023年9月到期，后续肯定会面临生物类似药的激烈竞争。 3 曾经的药王Humira Humira（阿达木单抗）是由艾伯维（AbbVie）开发的治疗多种炎症性疾病的单克隆抗体。它在全球范围内获批用于治疗包括类风湿性关节炎、强直性脊柱炎、银屑病、克罗恩病等在内的多种疾病。 Humira作为全球最畅销的药物之一，其销售额在2022年达到了212.4亿美元的最高峰，成为当之无愧的“药王”。然而，随着2023年其在美国的专利保护到期，Humira将面临生物类似药的竞争。在欧洲，Humira已经开始与生物类似药竞争，这对其销售额产生了一定影响。根据艾伯维Q2的财报披露，Humira Q2的销售额为28.1亿美元，与2023年同期相比，销售额下降了29.8%。在看前两个季度，其总销售额为50.8亿美元，同比下降32.7%，按照这个趋势，2024年Humira的销售额可能勉强能够站上100亿美元，看来类似药对其冲击还是比较大的。 4 Skyrizi（Risankizumab） Skyrizi同样是由艾伯维开发的单抗药物，该抗体靶向IL-23的p19亚基，从而选择性阻断体内免疫炎性介质白细胞介素-23（IL-23）介导的相关炎症。IL-23是一种参与炎症过程的细胞因子，被认为与多种慢性免疫介导的疾病有关。该药物自从2019年获批后，已经先后有多个适应症获批：1）中度至重度斑块状银屑病（Psoriasis）；2）活动性银屑病关节炎（Psoriatic Arthritis, PsA）；3）中度至重度克罗恩病（Crohn's Disease, CD）；4）中度至重度溃疡性结肠炎（Ulcerative Colitis, UC）。根据艾伯维Q2财报披露， Skyrizi第二季度的销售额接近27.3亿美元，与2023年同期相比，增加44.8%，而且其前半年销售额为47.35亿美元，直追Humira，与去年前半年相比，增幅达到46%。根据相关机构预处，Skyrizi2024年的销售额将会接近100亿美元，该药物将有力的补充Humira专利到期带来的冲击。 5 Cosentyx（secukinumab/可善挺） Cosentyx是由诺华开发的靶向IL-17A的单克隆抗体，其主要是通过抑制白细胞介素-17A（IL-17A）的活性来减少炎症和相关症状。Cosentyx已经有多个适应症获批：1）中度至重度斑块状银屑病（Psoriasis）；2）银屑病关节炎（Psoriatic Arthritis, PsA）；3）强直性脊柱炎（Ankylosing Spondylitis, AS）；4）放射学阴性中轴型脊柱关节炎（Non-radiographic axial spondyloarthritis, nr-axSpA）；5）化脓性汗腺炎（Hidradenitis Suppurativa, HS）；6）幼年特发性关节炎（Juvenile Idiopathic Arthritis, JIA）。根据诺华财报显示，Cosentyx第二季度的销售额达到15.26亿美元，该药物无论在美国还是美国之外的市场都表现出强劲的增长势头，与2023年同期相比，增加了22%。 6 Entyvio（vedolizumab/安吉优） Entyvio（通用名：vedolizumab，商品名：安吉优）是由武田开发的靶向整合素α4β7单抗，被批准用于治疗对传统治疗手段或抗肿瘤坏死因子治疗疗效不足或已经耐受的成人中度至重度活动性溃疡性结肠炎(UC)和克罗恩病(CD)等适应症。其通过特异性拮抗α4β7整合素，抑制其与肠道黏膜细胞粘附分子MAdCAM-1的结合，从而减少炎症细胞向肠道炎症部位的迁移。在国内，Entyvio已获得国家药品监督管理局（NMPA）的批准，用于治疗对传统治疗或TNFα抑制剂应答不充分、失应答或不耐受的中重度活动性UC和CD成人患者。虽然武田第二季度财报还美元披露，但是根据相关机构预处，Entyvio第二季度的销售额接近15亿美元左右，而且根据其第一季度披露，Entyvio同比增长了7.6%。 7 Xolair（奥马珠单抗） Xolair（奥马珠单抗）是一种靶向免疫球蛋白E（IgE）的重组人源化单克隆抗体，由罗氏（Roche）和诺华（Novartis）共同开发和销售。它主要用于治疗中度至重度持续性过敏性哮喘、慢性特发性荨麻疹（CIU）和慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）等过敏性疾病。 IgE是一种在过敏反应中起关键作用的抗体，它能够与体内的肥大细胞和嗜碱性粒细胞表面的高亲和力IgE受体（FcεRI）结合，当IgE与过敏原结合后，会导致这些细胞释放包括组胺在内的炎症介质，从而引发过敏症状。Xolair通过与IgE结合，阻止其与FcεRI的结合，从而减少过敏反应的发生。Xolair能够降低游离IgE的水平，减少FcεRI受体的数量，从而减少过敏原触发的炎症级联反应。根据罗氏第二季度财报披露，Xolair在第二季度的销售额为11.1亿瑞士法郎，同比增加10%。Xolair在美国和欧盟的专利已经过期，但目前市场上尚未有其生物类似药竞争产品上市。尽管面临专利到期的挑战，Xolair依然保持了稳定的销售额增长，这得益于其在多个适应症中的疗效和安全性，以及在新适应症上的不断拓展. 8 Orencia (Abatacept） Orencia（通用名：Abatacept，虽然单季度销售额没有超过10亿美元，但是也接近10亿美元，其在第二季度的销售额为9.48亿美元，Orencia是一种用于治疗类风湿性关节炎（RA）和其他自身免疫性疾病的生物制剂。它是首个通过靶向T细胞治疗RA的生物制剂，通过结合抗原呈递细胞（APCs）表面的CD80和CD86，阻断其与T细胞表面CD28的结合，从而抑制T细胞的激活。Orencia的这种作用机制有助于减少炎症和关节损伤，改善RA患者的症状。 Orencia由百时美施贵宝公司（Bristol-Myers Squibb）开发，最初于2005年在美国获得批准，用于治疗成人中度至重度活动性RA。此后，Orencia也被批准用于治疗幼年特发性关节炎（JIA）和成人银屑病关节炎（PsA）。在中国，Orencia（商品名：恩瑞舒®）由先声药业与百时美施贵宝合作开发，并已于2020年获得国家药品监督管理局（NMPA）的批准上市 9 Tremfya（guselkumab/特诺雅） Tremfya（guselkumab，商品名：特诺雅）和Orencia类似，单季度销售额虽然也没有过10亿美元，但是达到了9.1亿美元，其是由强生公司开发的一种选择性白细胞介素-23（IL-23）抑制剂，用于治疗中度至重度斑块状银屑病（PsO）和活动性银屑病关节炎（PsA）成人患者。Tremfya的作用机制是阻断IL-23的p19亚基，从而抑制其与IL-23受体的相互作用，减少炎症反应。在中国，Tremfya于2019年12月获得国家药监局（NMPA）批准上市，用于治疗适合系统性治疗的中重度斑块状银屑病成人患者。此外，Tremfya还被列入了NMPA药品审评中心（CDE）发布的《第一批临床急需境外新药名单》，治疗适应症包括红皮型银屑病、斑块型银屑病、脓疱型银屑病、银屑病关节炎、寻常型银屑病。 10 Rinvoq Rinvoq（Upadacitinib）虽然不是大分子，但是其是免疫治疗药物中唯一一个超过10亿美元的小分子，是由艾伯维（AbbVie）开发的一种Janus激酶（JAK）抑制剂，用于治疗多种炎症性疾病。自从2019年获得美国FDA批准以来，Rinvoq的销售额一直在稳步增长。 Rinvoq的销售额增长得益于其在多个适应症中的成功，包括类风湿性关节炎、银屑病关节炎、强直性脊柱炎、特应性皮炎、溃疡性结肠炎、非放射学中轴型脊柱关节炎和克罗恩病。随着Rinvoq在更多适应症中的应用和市场扩张，预计其销售额将继续增长。此外，Rinvoq被视为艾伯维的“药王”修美乐（Humira）的潜在继任者，随着修美乐专利到期和生物类似药的竞争，Rinvoq和Skyrizi（利生奇珠单抗）被艾伯维寄予厚望，以填补修美乐销售收入的减少。根据2024年上半年的业绩，其第二季度的销售额达到了14.3亿美元，前两个季度销售额为25.2亿美元，Rinvoq前两个季度的销售额同比增长60.4%，表现出强劲的增长势头。 11 总结感觉没啥好总结的，我们的制药道路任重而道远，别人很多药单季度都突破10亿美元了，我们好像还没有整年销售额超过10亿美元的药吧。药渡媒体商务合作媒体公关 | 新闻&会议发稿张经理：18600036371（微信同号）点击下方“药渡“，关注更多精彩内容免责声明 “药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！👇👇👇

财报临床3期免疫疗法上市批准

2024-09-16

·PipelineReview

Coya Therapeutics Announces Subcutaneously Administered COYA 302 Elicits Direct Anti-Inflammatory Effect in Brain in a Preclinical Inflammatory Mouse Model of Parkinson’s Disease

A key aspect of Parkinson’s disease (PD) pathophysiology is decreased systemic regulatory T cell (Treg) function with associated neuroinflammation in the nigrostriatal pathway of the brain, including the presence of reactive astrocytes and microglia that have an initiating and progressing role in PD; Subcutaneous injection of COYA 302, an anti-inflammatory, Treg-enhancing combination biologic (comprising low dose interleukin-2 and CTLA-4 Ig fusion protein), in an inflammatory mouse model of PD resulted in significant reductions in microglia and astrocyte activation in the nigrostriatal pathway in the brain; Importantly, study illustrates that peripheral administration of COYA 302 is directly immunomodulatory in the brain and associated with significant downregulation of neuroinflammation HOUSTON, TX, USA I September 16, 2024 I Coya Therapeutics, Inc. (NASDAQ: COYA) (“Coya” or the “Company”), a clinical-stage biotechnology company developing biologics intended to enhance regulatory T cell (Treg) function, announces the direct CNS anti-inflammatory effect of subcutaneously administered COYA 302 in a preclinical inflammatory associated mouse model of Parkinson’s Disease (PD). Coya’s Chief Business Officer and incoming Chief Executive Officer Arun Swaminathan, Ph.D. stated: “We believe that the ability of peripherally administered biologics (COYA 302) that potently and directly ameliorate the inflammatory milieu in the brain translates to strategies to suppress CNS neuro-inflammation beyond PD, including other inflammatory mediated neurodegenerative diseases such as Alzheimer’s disease (AD) and Frontotemporal Dementia (FTD).” Parkinson’s disease is characterized by the selective loss of dopaminergic neurons in brain regions responsible for motor control (nigrostriatal pathway), while inflammation and immune dysfunction from the associated loss of systemic Treg function are currently recognized as critical mediators of disease and subsequent progression of PD. Targeting the sustained proinflammatory mechanisms that progress the disease and enhance immunosuppressive cells, such as Tregs, may have the potential to provide disease-modifying benefits in patients with PD. In an inflammatory mouse model of PD, subcutaneous injections of COYA 302 significantly reduced inflammation and microglial activation in nigrostriatal brain regions responsible for motor control (dorsal striatum and substantia nigra). Microglial activation is an important mediator of PD and plays an important role in PD pathology and neurodegeneration. Microglial inhibition may hold promise as a therapeutic strategy to delay the progression of PD.Additionally, subcutaneous injections of COYA 302 resulted in reductions in astrocyte numbers and their activation (astrogliosis) in the nigrostriatal pathway. It is known that pathogenic astrocyte activation leads to neurodegeneration in PD, and mitigating its damage may be another therapeutic target. COYA 302’s direct effect in reducing neuroinflammatory constituents known to drive neurodegeneration is promising and warrants clinical translation into additional preclinical models and, ultimately, into patients. The Company anticipates presenting and/or publishing these data in a peer reviewing setting. About Parkinson’s Disease Parkinson’s disease (PD) is the most common movement disorder and the second most common neurodegenerative disease, affecting approximately 1% of individuals over the age of 60. Its prevalence increases significantly with age, and as the global population continues to age, the incidence of PD is expected to rise further. The hallmark of PD is the progressive degeneration of dopaminergic neurons, particularly in the substantia nigra, a region of the brain integral to the nigrostriatal pathway, which plays a crucial role in coordinating motor control. This neuronal loss leads to the characteristic motor symptoms of PD, such as bradykinesia, rigidity, and tremors, while patients also exhibit non-motor manifestations, such as cognitive decline, mood disturbances, and sleep disorders. While the exact cause of the dopaminergic neuron loss is not fully understood, growing evidence highlights chronic neuroinflammation and immune dysfunction as central drivers of PD pathogenesis and progression. A key aspect of PD pathophysiology is neuroinflammation in the nigrostriatal pathway, including the presence of reactive astrocytes. This neuroinflammation has long been considered a downstream response to the death of dopaminergic neurons. However, increased evidence suggests that astrocytes have an initiating role in PD pathophysiology. Regulatory T cells (Tregs), a subset of T cells responsible for maintaining immune homeostasis and preventing excessive immune responses, are decreased and impaired in PD patients and preclinical models. Subsequently, chronic pro-inflammatory immune cell activation, oxidative stress, and mitochondrial dysfunction all contribute to neuronal damage. The combination of targeting the chronic, proinflammatory activation and enhancing the Treg immunosuppressive function offers promising therapeutic potential for a disease-modifying therapy that could effectively alter the course of the disease, reduce neuronal loss, and improve patient outcomes. References 1. Kouli, Torsney, and Kuanl. Chapter 1 – Parkinson’s Disease: Etiology, Neuropathology, and Pathogenesis; Parkinson’s Disease: Pathogenesis and Clinical Aspects, Codon Publications, 2018 2. Booth, Hirst, and Wade-Martins. The Role of Astrocyte Dysfunction in Parkinson’s Disease Pathogenesis; Trends in Neuroscience , 2017 June, 40(6): 358-370 About COYA 302 COYA 302 is an investigational and proprietary biologic combination therapy with a dual immunomodulatory mechanism of action intended to enhance the anti-inflammatory function of regulatory T cells (Tregs) and suppress the inflammation produced by activated monocytes and macrophages. COYA 302 is comprised of proprietary low dose interleukin-2 (LD IL-2) and CTLA4-Ig fusion protein and is being developed for subcutaneous administration for the treatment of patients with ALS, AD, FTD, and PD. These mechanisms may have additive or synergistic effects. In February of 2023, Coya announced results from a proof-of-concept, open-label clinical study evaluating commercially available LD IL-2 and CTLA4-Ig fusion protein in a small cohort of patients with ALS conducted at the Houston Methodist Research Institute (Houston, Texas) by Stanley Appel, M.D., Jason Thonhoff, M.D., Ph.D., and David Beers, Ph.D. This study was the first-of-its-kind evaluating this dual-mechanism immunotherapy for the treatment of ALS. Patients in the study received investigational treatment for 48 consecutive weeks and were evaluated for safety and tolerability, Treg function, serum biomarkers of oxidative stress and inflammation, and clinical functioning as measured by the ALSFRS-R scale. During the 48-week treatment period, the therapy was well tolerated. The most common adverse event was mild injection-site reactions. No patient discontinued the study, and no deaths or other serious adverse events were reported. Patients’ disease progression was measured using the ALSFRS-R scale, a validated rating tool for monitoring the progression of disability in patients with ALS. The mean (±SD) ALSFRS-R scores at week 24 (33.75 ±3.3) and week 48 (32 ±7.8) after initiation of treatment were not statistically different compared to the ALSFRS-R score at baseline (33.5 ±5.9), suggesting significant amelioration in the progression of the disease over the 48-week treatment period. Treg suppressive function, expressed as percentage of inhibition of proinflammatory T cell proliferation, showed a statistically significant increase over the course of the treatment period and was significantly reduced at the end of the 8-week washout post-treatment period. Treg suppressive function at 24 weeks (79.9 ±9.6) and 48 weeks (89.5 ±4.1) were significantly higher compared to baseline (62.1 ±8.1) (p<0.01), suggesting enhanced and durable Treg suppressive function over the course of treatment. In contrast, Treg suppressive function (mean ±SD) was significantly decreased at the end of the 8-week washout period compared to end-of-treatment at week 48 (70.3 ±8.1 vs. 89.5 ±4.1, p <0.05). The study also evaluated serum biomarkers of inflammation, oxidative stress, and lipid peroxides. The available data up to 16 weeks after initiation of treatment suggest a decrease in these biomarker levels, which is consistent with the observed enhancement of Treg function. The evaluation of the full biomarker data is ongoing. COYA 302 is an investigational product not yet approved by the FDA or any other regulatory agency. About Coya Therapeutics, Inc. Headquartered in Houston, TX, Coya Therapeutics, Inc. (Nasdaq: COYA) is a clinical-stage biotechnology company developing proprietary treatments focused on the biology and potential therapeutic advantages of regulatory T cells (“Tregs”) to target systemic inflammation and neuroinflammation. Dysfunctional Tregs underlie numerous conditions, including neurodegenerative, metabolic, and autoimmune diseases, and this cellular dysfunction may lead to sustained inflammation and oxidative stress resulting in lack of homeostasis of the immune system. Coya’s investigational product candidate pipeline leverages multiple therapeutic modalities aimed at restoring the anti-inflammatory and immunomodulatory functions of Tregs. Coya’s therapeutic platforms include Treg-enhancing biologics, Treg-derived exosomes, and autologous Treg cell therapy. COYA 302 – the Company’s lead biologic investigational product or “Pipeline in a Product” – is a proprietary combination of COYA 301 (Coya’s proprietary LD IL-2) and CTLA4-Ig for subcutaneous administration with a unique dual mechanism of action that is now being developed for the treatment of Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson’s Disease, and Alzheimer’s Disease. Its multi-targeted approach enhances the number and anti-inflammatory function of Tregs and simultaneously lowers the expression of activated microglia and the secretion of pro-inflammatory mediators. This synergistic mechanism may lead to the re-establishment of immune balance and amelioration of inflammation in a sustained and durable manner that may not be achieved by either low-dose IL-2 or CTLA4-Ig alone. For more information about Coya, please visit www.coyatherapeutics.com SOURCE: Coya Therapeutics

临床结果免疫疗法细胞疗法

100 项与阿巴西普相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03203	阿巴西普	L04AA24	DB01281

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
急性移植物抗宿主病	美国	Bristol Myers Squibb Co.	2021-12-15
幼年特发性关节炎	美国	Bristol Myers Squibb Co.	2009-08-25
银屑病关节炎	欧盟	Bristol-Myers Squibb Pharma EEIG	2007-05-21
银屑病关节炎	冰岛	Bristol-Myers Squibb Pharma EEIG	2007-05-21
银屑病关节炎	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2007-05-21
银屑病关节炎	挪威	Bristol-Myers Squibb Pharma EEIG	2007-05-21
多关节型幼年特发性关节炎	欧盟	Bristol-Myers Squibb Pharma EEIG	2007-05-21
多关节型幼年特发性关节炎	冰岛	Bristol-Myers Squibb Pharma EEIG	2007-05-21
多关节型幼年特发性关节炎	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2007-05-21
多关节型幼年特发性关节炎	挪威	Bristol-Myers Squibb Pharma EEIG	2007-05-21
类风湿关节炎	美国	Bristol Myers Squibb Co.	2005-12-23

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
心肌炎	临床3期	美国	Bristol Myers Squibb Co.	2022-06-22
心肌炎	临床3期	加拿大	Bristol Myers Squibb Co.	2022-06-22
风湿性多肌痛	临床3期	法国	Bristol Myers Squibb Co.	2018-12-13
巨细胞动脉炎	临床3期	美国	Bristol Myers Squibb Co.	2017-07-15
巨细胞动脉炎	临床3期	澳大利亚	Bristol Myers Squibb Co.	2017-07-15
巨细胞动脉炎	临床3期	奥地利	Bristol Myers Squibb Co.	2017-07-15
巨细胞动脉炎	临床3期	比利时	Bristol Myers Squibb Co.	2017-07-15
巨细胞动脉炎	临床3期	保加利亚	Bristol Myers Squibb Co.	2017-07-15
巨细胞动脉炎	临床3期	加拿大	Bristol Myers Squibb Co.	2017-07-15
巨细胞动脉炎	临床3期	丹麦	Bristol Myers Squibb Co.	2017-07-15

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临床结果

适应症

分期

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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


NCT03882008 (CTgov)	临床4期	类风湿关节炎	25	Abatacept	積鑰簾鏇蓋範鏇願窪觸(衊餘鹹淵獵夢廠齋衊糧) = 憲簾廠憲襯獵衊壓鹹鬱選顧鹹鏇鏇夢壓艱蓋蓋 (繭製餘製願鹽醖淵觸餘, 艱鑰願襯網艱壓壓衊顧 ~ 鬱簾願網餘範簾醖鹽夢) 更多	-	2024-07-30
NCT04909801 (AMPLIFIED, EULAR2024) 人工标引	临床3期	类风湿关节炎	338	Abatacept+Methotrexate	膚鏇鑰艱製襯顧鏇遞簾(壓艱襯憲衊鑰網遞鏇觸) = 鑰夢選廠鬱廠廠繭積繭觸鏇廠遞積糧糧鑰網憲 (觸顧鑰鹹艱壓餘選醖觸 ) 未达到更多	非优	2024-06-12
				Adalimumab+Methotrexate	膚鏇鑰艱製襯顧鏇遞簾(壓艱襯憲衊鑰網遞鏇觸) = 夢廠積憲憲鏇遞襯艱製觸鏇廠遞積糧糧鑰網憲 (觸顧鑰鹹艱壓餘選醖觸 ) 未达到更多
NCT04120831 \| EUCTR2018-003877-91-DE (TOLERA, EULAR2024) 人工标引	临床2期	类风湿关节炎 ACPA-positive	20	Rituximab+Abatacept+Methotrexate	構鏇淵膚繭鹹膚製鹽夢(鬱簾獵選網繭鏇鹹窪齋) = 壓鹹鑰膚構繭願鬱願艱廠壓簾範艱衊憲襯淵繭 (積廠窪顧積製選艱構淵, 441.64) 更多	不佳	2024-06-12
				Rituximab+Methotrexate	構鏇淵膚繭鹹膚製鹽夢(鬱簾獵選網繭鏇鹹窪齋) = 膚齋憲鏇壓鹹齋餘鏇選廠壓簾範艱衊憲襯淵繭 (積廠窪顧積製選艱構淵, 51.98) 更多
EULAR2024	N/A	癌症	-	Abatacept	觸膚淵醖淵糧衊廠艱蓋(鏇餘選鬱淵顧鑰蓋網製) = highlighted an increased risk of non-melanoma skin cancer (NMSC) with abatacept, compared with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) 鹽齋鹹艱醖襯窪壓壓糧 (鹹鹹窪鹽鹹醖遞夢鏇襯 )	-	2024-06-05
				Placebo
EULAR2024	N/A	ACPA-positive	92	ABT	鬱積願襯獵夢壓顧壓選(鏇鹹衊選壓遞範夢鹹夢) = 醖簾遞範網鏇選艱製鹽壓選願鏇觸淵壓齋醖餘 (積夢鹹觸壓構鹽網鬱鏇 ) 更多	积极	2024-06-05
EULAR2024	N/A	进行性肺纤维化	526	Abatacept	製觸製襯鹽襯窪鏇襯獵(襯齋襯衊獵繭餘鑰願窪) = 鬱膚鑰糧餘憲範餘製鹽鬱積襯襯遞鏇鹽願觸齋 (餘選壓積鹽構醖襯醖廠 )	积极	2024-06-05
EULAR2024	N/A	类风湿关节炎	-	Methotrexate + Abatacept	膚襯範壓願鏇餘淵繭觸(網鑰觸繭顧艱鬱積膚鹹) = 觸網繭鏇淵範築製壓繭鹽構憲築鹽鬱獵觸鬱獵 (廠獵醖襯淵鏇膚餘鹹顧, 346 ~ 1719) 更多	-	2024-06-05
EULAR2024	N/A	类风湿关节炎	-	Abatacept	鏇願醖繭獵繭獵製襯鹽(積選構齋衊窪選蓋鬱積) = 鏇齋襯艱醖糧醖願觸衊積窪網製繭膚夢膚觸齋 (鏇積鏇積願繭壓獵獵夢 ) 更多	积极	2024-06-05
				Methotrexate	鏇願醖繭獵繭獵製襯鹽(積選構齋衊窪選蓋鬱積) = 遞遞鹽構願鹹窪積遞遞積窪網製繭膚夢膚觸齋 (鏇積鏇積願繭壓獵獵夢 ) 更多
EULAR2024	N/A	类风湿关节炎	-	rituximab	憲觸範選淵廠襯選餘鏇(網衊糧顧齋糧襯鬱蓋遞) = 繭廠廠夢製膚遞鏇鬱醖網選繭醖構簾膚積廠糧 (夢糧醖簾壓遞壓範醖積, -4.5 ~ 6.7)	积极	2024-06-05
				abatacept	憲觸範選淵廠襯選餘鏇(網衊糧顧齋糧襯鬱蓋遞) = 鹹顧構鑰糧願窪憲窪選網選繭醖構簾膚積廠糧 (夢糧醖簾壓遞壓範醖積, -2.6 ~ 9.2)
NCT06307301 (Pubmed) 人工标引	临床1期	肌萎缩侧索硬化 4-Hydroxynonenal \| Neurofilament Light Chain	4	Abatacept + Interleukin-2	醖艱鬱製廠鑰鬱壓鏇觸(簾蓋鏇鹽衊醖獵簾蓋齋) = 鑰膚鑰糧艱齋顧夢膚壓鏇糧壓餘衊製鏇壓壓艱 (壓獵襯鬱鬱衊窪鏇醖壓 ) 更多	积极	2024-06-01