A randomized placebo-controlled double-blind phase III two-arm study to investigate the reduction of Monthly Migraine Days (MMDs) over 12 weeks of treatment with combination of CGRP mAbs and onabotulinumtoxin A intramuscularly compared with CGRP mAbs and placebo in male and female participants with chronic migraine aged 18-70 years.

开始日期2025-06-06

申办/合作机构-

NCT06237062

/ TerminatedN/A

Real-world Experience of Patients Newly Started on Erenumab in the Gulf Region: a Longitudinal Prospective Observational Study

The objective of this study was to evaluate the effect of erenumab on medication-specific treatment satisfaction in patients who newly started on erenumab over 12 weeks

开始日期2024-06-05

申办/合作机构

Novartis Pharmaceuticals Canada, Inc.

NCT06212661

/ Enrolling by invitationN/AIIT

Migraine Medication Effects on Urinary Symptoms

A prospective observational cohort trial to study the effects of CGRP inhibitors (CGRPi) on lower urinary tract symptoms (LUTS) and bladder/pelvic pain. Candidates for either CGRPi or an alternative therapy for refractory migraines (OnabotulinumtoxinA (BoNTA) extracranial muscle injections) with baseline LUTS will be recruited. The investigators will assess LUTS and pelvic pain using validated symptom and quality-of-life questionnaires, pretreatment and at 3 months post-treatment follow-up, comparing change in symptoms based on treatment received.

开始日期2024-04-05

申办/合作机构

The Cleveland Clinic Foundation

100 项与依瑞奈尤单抗相关的临床结果

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100 项与依瑞奈尤单抗相关的转化医学

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100 项与依瑞奈尤单抗相关的专利（医药）

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575

项与依瑞奈尤单抗相关的文献（医药）

2026-06-01·SLEEP MEDICINE REVIEWS

Sleep and anti-calcitonin gene related peptide (CGRP) drugs: current evidence and perspectives

Review

作者: Romozzi, Marina ; Boccalini, Alberto ; Vernieri, Fabrizio ; Geppetti, Pierangelo ; Sebastianelli, Gabriele ; Ray, Sucharita ; Vigani, Giulia ; Altamura, Claudia ; Iannone, Luigi Francesco ; Viticchi, Giovanna

Migraine and sleep share a bidirectional relationship: sleep disruption can trigger migraine attacks, while migraine impairs sleep continuity and quality. Calcitonin gene-related peptide (CGRP), central to migraine pathophysiology, also contributes to sleep regulation through hypothalamic and brainstem circuits that control arousal and circadian rhythms. This overlap raises the question of whether pharmacological inhibition of CGRP with monoclonal antibodies (mAbs) or gepants could affect sleep. This scoping review summarizes evidence on anti-CGRP therapies and their impact on sleep quality, efficacy, and tolerability. Although results are inconsistent across instruments, emerging data suggest that anti-CGRP mAbs and gepants, particularly erenumab, galcanezumab, and atogepant, can improve subjective sleep quality and objective measures such as sleep efficiency in some cases. Evidence for fremanezumab and eptinezumab remains scarce, whereas large-scale pharmacovigilance datasets indicate low rates of insomnia, somnolence, or abnormal dreams. Overall, current findings suggest that CGRP inhibition impacts the sleep system, but the mechanisms of this interaction remain partly understood, representing a promising area for mechanistic exploration and clinical application. Future studies with standardized sleep endpoints are needed to distinguish direct neuropharmacological effects from indirect benefits mediated by improvement in migraine burden.

2026-04-01·Neurology-Clinical Practice

Effect of Erenumab on Patient-Reported Outcomes in Episodic Migraine in Asia, the Middle East, and Latin America

Article

作者: Tai, Mei-Ling Sharon ; Zhao, Yi Jing ; Wen, Shihua ; Roxas, Artemio A. ; Saravia, Bibiana ; Su, Wendy ; Kim, Byung Kun ; Tran, Tai Ngoc ; Chowdhury, Debashish ; Mondal, Subhayan ; Riachi, Naji J. ; Tanprawate, Surat ; Arkuszewski, Michal ; Ecochard, Laurent ; Wang, Shuu-Jiun

Background and Objectives:

Migraine is a significant disabling neurologic headache disorder globally. Evaluating patient-related outcomes (PROs) is necessary to assess the impact of therapeutic interventions in preventive therapy. An exploratory analysis of data from the EMPOwER study examined the effect of erenumab on PROs in patients with episodic migraine (EM) in regions underrepresented in the pivotal Phase 3 trials of erenumab, specifically Asia, the Middle East, and Latin America.

Methods:

Patients (N = 900) were randomized (2:3:3) to receive monthly subcutaneous injections of erenumab 140 mg, erenumab 70 mg, or placebo. Adjusted mean changes from baseline in the Headache Impact Test (HIT-6), Migraine Physical Function Impact Diary (MPFID), modified Migraine Disability Assessment (mMIDAS), and EuroQoL 5-dimension 5-level scale (EQ-5D-5L) scores were assessed during the double-blind treatment phase of 3 months.

Results:

A statistically significant reduction from baseline in the HIT-6 total score was observed for erenumab 140 mg (-9.34, p < 0.001) and 70 mg (-8.39, p = 0.004) vs placebo (-6.62) at Month 3. Improvement in MPFID scores was also greater in the erenumab groups vs the placebo group (Everyday Activity: 140 mg, -5.61 [p = 0.002]; 70 mg, -4.94 [p = 0.011]; placebo, -3.19; Physical Impairment: 140 mg, -4.27 [p = 0.014]; 70 mg, -3.95 [p = 0.021]; placebo, -2.31) at Month 3. Similar findings were observed for mMIDAS scores (140 mg -8.99 [p < 0.001], 70 mg -8.11 [p = 0.011] vs placebo [-6.59]) and the EQ-5D-5L quality-of-life visual analog scale scores (140 mg 8.13 [p = 0.017], 70 mg 7.08 [p = 0.088] vs placebo [5.22]), although no meaningful between-group difference was noted for index values.

Discussion:

Erenumab showed favorable effects on PROs when compared with placebo in patients with EM. These results enhance the evidence for erenumab as an effective preventive therapy for patients with EM.

Trial Registration Information:

Clinicaltrials.gov/study/NCT03333109.

2026-03-01·HEADACHE

Comprehensive assessment of erenumab efficacy in participants with high‐frequency episodic migraine with at least one previously failed preventive treatment: The EMBRACE study

Article

作者: Dodick, David W. ; Paiva da Silva Lima, Gabriel ; Chehrenama, Mahan ; Chou, Denise E. ; Zhu, Yineng ; Khodavirdi, Ani C. ; Szklener, Sebastian ; Rao, Renata ; Nastaj, Marcin ; Bhatia, Ajay K. ; Tassorelli, Cristina ; Szabó, Gyöngyi

Abstract:

Objective:

To evaluate the effect of erenumab treatment beyond monthly migraine days in patients with high‐frequency episodic migraine who did not respond to at least one previous migraine preventive treatment.

Background:

Reduction in monthly migraine days has been the efficacy standard for migraine preventive treatments; however, it does not fully capture the holistic benefit of the therapy. Erenumab, a monoclonal antibody targeting the calcitonin gene–related peptide pathway, has demonstrated reduction in monthly migraine days and improvement in function in patients with episodic and chronic migraine.

Methods:

In this phase 4, interventional, double‐blind, randomized, placebo‐controlled, multicenter, global study, treatment with erenumab was assessed over 4 months in adults with high‐frequency episodic migraine. The study was conducted at 61 sites located across North America and Europe between September 2020 and October 2023. Patients with ≥1 qualifying oral triptan‐treated migraine attack at baseline were randomized to receive erenumab 140 mg or placebo subcutaneously once monthly. The primary endpoint was change from baseline in mean monthly hours of at least moderate headache pain intensity over months 1, 2, and 3; secondary endpoints included change from baseline in mean monthly function, mean monthly duration of at least moderate pain intensity in migraine attacks, and mean monthly peak migraine pain intensity. Safety outcomes were also assessed.

Results:

Of 512 randomized patients, 510 received erenumab 140 mg ( n = 254) or placebo ( n = 256) once monthly. Demographics and baseline characteristics were balanced between the two treatment arms. Erenumab 140 mg was superior to placebo in reducing duration of moderate or severe headache pain intensity over months 1, 2, and 3 (least squares mean [95% confidence interval {CI}] difference, −7.95 [−11.45, −4.46]; p < 0.001). Compared with placebo, erenumab significantly reduced migraine functional impact as assessed by the four domains of the Migraine Functional Impact Questionnaire, with a least squares mean (95% CI) difference of −7.36 (−10.80, −3.92) for physical functioning, −7.10 (−10.34, −3.87) for usual activities, −6.82 (−10.37, −3.27) for social functioning, and − 7.05 (−10.76, −3.34) for emotional functioning ( p < 0.001 for all domains). Significant reductions with erenumab compared with placebo were also observed in duration of at least moderate pain intensity in residual or break‐through migraine attacks (least squares mean [95% CI] difference, −1.07 [−1.92, −0.22]; p = 0.013) and peak migraine pain intensity (−0.48 [−0.85, −0.11]; p = 0.011). Incidence of grade 3 adverse events was 1.6% with erenumab and 1.2% with placebo; no grade 4 or fatal adverse events were reported in either treatment arm.

Conclusion:

Findings from the EMBRACE study demonstrated that treatment with erenumab in patients with high‐frequency episodic migraine can provide positive therapeutic effects on ictal burden and pain, with residual migraine attacks tending to be shorter and less painful, with less overall impact.

172

项与依瑞奈尤单抗相关的新闻（医药）

2026-03-30

·周超医生

头痛文献追踪：偏头痛生物制剂长期用药安全吗？最新研究给出答案

在偏头痛治疗领域，抗CGRP（降钙素基因相关肽）单克隆抗体的问世无疑是一场革命。作为神经内科医生，我们既欣喜于这类药物为患者带来的显著疗效，也必须审慎关注其长期安全性。这篇文献带来的系统评价为我们提供了重要参考。研究背景：从临床需求到证据缺口偏头痛作为全球致残性最高的神经系统疾病之一，其预防治疗始终面临挑战。约40%的患者需要长期预防性治疗，而传统口服药物常因耐受性问题导致治疗中断。自2018年首个抗CGRP受体单抗erenumab上市以来，这类靶向药物显著改变了临床实践格局。然而，随着临床应用时间的延长，一个重要问题日益凸显：长期使用（超过12个月）的安全性证据是否充分？研究方法：严谨的科学态度这项由欧洲头痛联合会主导的研究采用了系统评价和Meta分析方法，检索了2013年至2025年4月期间的主要医学数据库。研究团队制定了严格的纳入标准：• 治疗持续时间必须≥12个月• 包含随机对照试验、开放标签扩展研究及观察性研究• 明确报告安全性终点指标最终从1499条记录中筛选出14篇符合要求的文献，对应11项独立研究，共涉及4379名患者，最长观察时间达5年。这张PRISMA流程图展现了系统性文献筛选的全过程，其价值不仅在于展示最终纳入的14篇文献，更揭示了循证医学研究的严谨性。从初始检索的1499条记录到最终符合标准的14篇文献，这个层层筛选的过程体现了高质量Meta分析的标准操作流程。特别值得注意的是，研究团队专门检索了ClinicalTrials.gov数据库，这一做法确保了未发表研究的纳入，有效避免了发表偏倚。作为临床研究者，我深刻理解这种全面检索策略对保证证据完整性的重要意义。流程图底部的"14 studies included in qualitative synthesis"提示我们，虽然最终纳入研究数量有限，但这正反映了目前抗CGRP单抗长期安全性证据仍处于积累阶段。核心发现：数据说话治疗持续性分析汇总分析显示，抗CGRP单抗的全因停药率为23%，这一数据在慢性疾病预防治疗中处于可接受范围。更重要的是，因不良事件导致的停药率仅为3%，显著低于传统口服预防药物。这幅森林图直观展示了各研究中全因停药率的分布情况。每个水平线段代表单个研究的95%置信区间，菱形符号表示汇总效应量。最引人注目的是研究间巨大的异质性（I²=97.3%），这反映了真实世界中停药原因的多样性。从临床实践角度，23%的汇总停药率需要结合具体背景理解。停药原因包括疗效不足、患者个人决策、保险报销问题等多项因素。值得注意的是，不同研究的置信区间宽度差异显著，这与样本量大小直接相关。样本量较大的研究（如Gaul 2024）其估计精度明显更高。这种异质性提醒我们，在向患者解释治疗预期时，需要个体化考量各种可能影响治疗持续性的因素。安全性特征随时间演变研究观察到，不良事件相关停药率在治疗第一年后保持稳定（<5%），未随治疗时间延长而增加。任何不良事件的发生率在基线时较高（>70%），但长期随访中未见进一步上升趋势。这张时间趋势图包含两个重要信息：AE相关停药率的时间变化和报告AE数量的时间分布。上图显示AE相关停药率在治疗第一年后保持稳定，未随治疗时间延长而增加，这一发现对长期治疗的安全性评估至关重要。下图显示报告AE数量在早期较高，随后趋于平稳。这种现象可能反映：早期AE包含了一过性反应，长期治疗中未出现新的安全信号；患者对治疗的适应性逐渐形成；临床医生对AE的管理经验不断积累。从临床管理角度，这一趋势提示我们需要在治疗初期加强AE监测和患者教育，而随着治疗时间延长，关注重点可以适当调整。不良事件谱系分析最常见的不良事件为上呼吸道感染（20.4%），其次为疼痛相关症状（3.8%）和胃肠道症状（2.5%）。大多数不良事件类别发生率低于3%，且严重不良事件罕见。值得注意的是，大多数AE类别的发生率低于3%，且严重AE罕见。各AE类型的置信区间普遍较宽，反映了不同研究间AE定义的差异和发生率的不确定性。这种不确定性在临床实践中需要转化为个体化监测策略。作为临床医生，我们应当重点关注那些可能导致治疗中断的AE，如持续性便秘、注射部位反应等，同时也要认识到大多数AE是轻微且可管理的。临床启示：从证据到实践风险偏倚的客观评估所有纳入研究均存在一定偏倚风险，主要源于研究设计局限性。开放标签扩展研究存在"应答者选择偏倚"，而真实世界研究则难以避免混杂因素影响。研究者使用ROBINS-I工具进行了系统评估，为结果解读提供了重要参考。各类单抗的特异性分析研究对不同单抗进行了亚组分析，发现erenumab、eptinezumab、fremanezumab和galcanezumab的安全性特征基本相似，但个别不良事件（如便秘）的发生率存在差异。这种差异既可能反映药物特性，也可能与研究设计和人群特征相关。局限性与展望需要指出的是，当前证据存在不均衡性——多数研究聚焦于erenumab，其他单抗的长期数据相对有限。此外，COVID-19大流行可能对呼吸道感染相关不良事件的报告产生干扰。未来需要更多针对不同单抗的长期研究，以及标准化的不良事件报告体系。真实世界监测和登记研究将继续发挥重要作用，特别是对罕见不良事件的识别。临床实践建议基于现有证据，抗CGRP单抗在偏头痛长期预防中展现出良好的风险-获益特征。作为临床医生，我们建议：1. 个体化治疗决策：结合患者具体情况和药物特性选择合适单抗2. 长期监测：建立规范的随访计划，重点关注常见不良事件3. 患者教育：如实告知药物安全性特征，管理治疗期望这项研究为抗CGRP单抗的长期安全性提供了重要证据支持，增强了我们在临床实践中信心。随着更多长期数据的积累，我们有望进一步优化偏头痛的长期管理策略。文献出处：105.Decoding the long-term safety of anti-CGRP (receptor) mAbs: a meta-analysis and systematic review. J Headache Pain. 2026 Jan 3;27(1):10. doi: 10.1186/s10194-025-02256-0. PMID: 41484941; PMCID: PMC12776973.（AI辅助编译）

2026-03-27

·小药说药

GPCR药物发现：新药、新靶点与新适应症

-01- 引言 G蛋白偶联受体（GPCR）构成了最大的药物靶标家族之一，反映了它们在众多病理生理过程中的参与度。本文综述了GPCR超家族的药物发现趋势，涵盖了已获得监管批准或正在临床试验中研究的化合物、靶点和适应症。分析发现，目前有516种获批药物靶向GPCR，占所有获批药物的36%。这些药物作用于121个GPCR靶点，占所有非感官GPCR的三分之一。此外，针对133个GPCR（包括30个新靶点）的337种药物正处于临床试验阶段，这表明未来获批药物的数量将持续增长。 -02- 一、历史背景 GPCR形成一个包含约800种膜蛋白的超家族，它们被细胞外刺激激活，共享典型的七螺旋跨膜结构域，并主要与细胞内转导蛋白（如G蛋白和抑制蛋白）偶联。大多数GPCR具有共同的进化起源，共同参与复杂的信号系统，调节无数的生理和病理生理过程。因此，GPCR一直是所有主要治疗领域的常用靶标，超过30%的获批药物靶向GPCR。 GPCR相关药物开发的历史可以追溯到“GPCR”一词被创造之前。最早有文献记载的GPCR作用制剂研究可追溯到19世纪，描述了1805年吗啡和1875年毛果芸香碱的分离及医疗应用。20世纪中叶，发现了由被称为“肾上腺素能受体”的实体介导的肾上腺素分子功能。1980年代末和1990年代，药物-靶标相互作用理解的进步揭示了配体不仅可以选择性激活特定受体，还可以选择性触发不同的细胞内转导蛋白，这为“偏向信号”这一新范式铺平了道路。此外，研究显示配体可以结合在生理配体结合位点（“正构”位点）之外的远处“变构”位点，这些机制为设计副作用更少的药物提供了机会。 2000年牛视紫红质和2007年β2 -肾上腺素能受体的首批X射线晶体结构的报道，揭示了其整体高分辨率架构，提供了机制见解并使基于结构的药物设计成为可能。近年来，随着冷冻电子显微镜和核磁共振技术的进步，针对GPCR的生物制剂（如单克隆抗体）研发也获得了动力，2018年FDA批准了首个靶向GPCR的单抗Erenumab用于预防偏头痛。 -03- 二、获批药物与靶点概览 1. 获批药物统计目前在北美、欧洲、亚洲和澳大利亚市场上有516种不同的药物靶向GPCR用于治疗。这些靶向GPCR的药物约占所有获批药物的36%，略高于此前报道的30-33%。在过去5年（自2019年以来），有37种靶向GPCR的新药获得批准，其中包括7个首次获批的受体：胃抑制多肽（GIP）受体（GIPR）、GPRC5D、C5A、神经激肽-3（NK3）以及黑素皮质素受体3、4和5（MC3/4/5）。最近批准的是KarXT（Cobenfy），这是一种xanomeline（M4毒蕈碱乙酰胆碱受体选择性激动剂）和trospium（外周毒蕈碱拮抗剂）的组合，是首个治疗精神分裂症的同类药物。 2. 临床试验中的药物基于ClinicalTrials.gov的数据，目前有337种药物正处于临床试验阶段，其中172种为新药，165种为老药新用药物。在新药中，分别有51、76和45种药物进入了I期、II期和III期临床试验。 3. 靶点分布总体而言，已有121个GPCR被“成药化”，即成为获批药物的靶点，占所有362个非感官人类GPCR的三分之一。此外，目前有133个GPCR正被临床试验中的药物靶向，其中30个尚未有获批药物靶向它们。值得注意的是，共有151个临床GPCR靶点，主要属于A类（130个），其次是B1类（13个）、C类（7个）和F类（1个）。目前尚无靶向B2类/粘附GPCR的药物进入临床试验。 -04- 三、畅销药物与主要靶点 1. 畅销药物在2023年销量前50的药物中，有5种靶向GPCR的产品。其中Entresto（沙库巴曲/缬沙坦）用于心力衰竭和高血压。另外四种产品（含三种独特化合物）的适应症为代谢疾病领域：2型糖尿病和肥胖症，包括Ozempic（司美格鲁肽）、Trulicity（度拉糖肽）、Mounjaro（替尔泊肽）和Wegovy（司美格鲁肽）。值得注意的是，这三种化合物均靶向GLP-1受体，而替尔泊肽还作用于GIP受体。2023年，靶向GPCR的糖尿病和肥胖症药物销售额接近300亿美元。 2. 主要靶点为了确定哪些GPCR被“成药”最多，研究识别了获批药物数量最多的靶点。排名前十的GPCR均有41至65种获批药物，且均属于胺能受体亚家族，由多巴胺、组胺、肾上腺素、血清素或乙酰胆碱激活。这些靶点的获批药物众多，反映了它们是最早被发现、获得药理学分析并进行结构表征的受体之一。 -05- 四、新药与新靶点的趋势 1. 新型药物的特性通过对临床试验中药物的分析，发现了一些显著趋势：靶点选择性：与2017年的分析相比，新药进入临床试验显示出更强的选择性趋势。惊人的是，77%的新药只有一个靶点，20%有两个靶点，仅3%有三个或更多靶点。变构调节剂比例增加：在新药中，变构调节剂的比例（8%）显著高于所有获批药物（1%）。变构调节提供了增加亚型选择性的优势，因为变构结合位点比正构位点保守性更低。目前有14种变构调节剂正在针对A类和C类GPCR进行研究，覆盖精神分裂症、阿尔茨海默病、肥胖症等多种适应症。抗体和蛋白/肽类比例增长：与获批药物相比，新药中抗体的比例更高（10%对1%），蛋白/肽类的比例也更高（19%对12%），相应的小分子比例较少（71%对87%）。激动性抗体和纳米抗体有望特异性激活GPCR，提供比传统小分子更高的选择性和更长的半衰期。 2. 新型靶点目前有30个尚未有任何获批药物的GPCR正被临床试验中的药物靶向，其中最大的一组是A类GPCR，包含9个趋化因子受体。其他新型A类GPCR靶点包括胆囊收缩素受体CCK2 、白三烯受体BTL1−2 、血管紧张素受体AT2 、Apelin受体、铃蟾肽受体BB2等。此外，还包括孤儿受体GPR6、GPR52、GPR84、MAS1、MRGPRX2和MRGPRX4。例如，CVN424靶向GPR6用于帕金森病，EP262靶向MRGPRX2用于荨麻疹治疗。 -06- 五、药物再利用与GPCR重靶向 1. 药物再利用药物再利用定义为已获批药物用于新适应症，可能因利用现有的安全性概况而降低开发时间、成本和风险。目前，在516种获批的GPCR靶向药物中，有165种正在I期、II期或III期试验中测试新适应症。再利用药物占临床试验所有化合物的近一半（49%），表明再利用是GPCR靶向药物开发的主要驱动力。例如，大麻二酚是研究最广泛的再利用药物，有29种适应症正在研究中；催产素正在研究用于精神分裂症和PTSD；普萘洛尔则被研究用于癌症和罕见病。 2. GPCR重靶向目前临床试验中的337种GPCR靶向药物作用于133个不同的GPCR，其中103个（77%）已是获批药物的靶点。这反映了从胺能受体向肽/蛋白受体的转移。在获批药物数量最多的前十大靶点中，只有5-HT2A 受体和β2-肾上腺素能受体也出现在当前临床试验药物数量最多的前15个靶点中。这种转移可能归因于胺能受体的饱和，以及肽/蛋白配体的GPCR数量多于小分子配体的GPCR。 3. 关键受体家族 GLP-1R, GLP-2R, GIPR和GCGR：针对这些受体的药物（如司美格鲁肽、替尔泊肽）是顶级畅销药。替尔泊肽是首个获批的GLP-1R/GIPR双重激动剂，目前还有11种双重GLP-1R/GCGR激动剂处于I至III期试验中，以及两种三重激动剂正在评估中。食欲素受体：食欲素受体OX1和OX2参与多种神经和精神疾病的病理生理学。已获批的药物（如Suvorexant）是双重OX1和OX2拮抗剂，用于治疗失眠。目前，选择性OX1拮抗剂正在研究用于阿片类药物使用障碍，选择性OX2拮抗剂正在研究用于失眠和抑郁症。 -07- 六、适应症格局 1. 主要适应症根据解剖学治疗化学（ATC）代码分类，获批药物数量最多的主要适应症包括精神抑制药（58种）、眼科用药（44种）、全身用抗组胺药（43种）、镇痛药（42种）和阻塞性气道疾病药物（38种）。根据ICD11分类，获批药物数量最多的疾病领域是症状/体征（132种）、循环系统疾病（86种）、精神/行为/神经发育障碍（81种）和神经系统疾病（72种）。 2. 适应症趋势过去20年获批的药物在糖尿病、便秘、免疫抑制剂和抗肿瘤药物等适应症中占相当大比例。这反映了GPCR在癌症中作用的认知加深，以及GLP-1R激动剂等药物在代谢领域的成功。 3. 疾病领域的临床试验分布在某些疾病领域，临床试验中的药物比例相对于获批药物较高，例如发育异常、肌肉骨骼系统疾病、内分泌/营养/代谢疾病、肿瘤等，这些领域超过50%的化合物处于试验阶段。相反，在循环系统疾病和免疫系统疾病中，获批药物的比例远高于试验中的药物。临床试验中药物数量最多的领域是精神/行为/神经发育障碍（71种）、神经系统疾病（66种）、内分泌/营养/代谢疾病（52种）和肿瘤（50种）。 4. 特定疾病领域的突破糖尿病药物：靶向GPCR的糖尿病药物虽然数量不多（8种），但影响巨大，如司美格鲁肽和替尔泊肽。免疫调节剂：已有5种GPCR药物获批作为免疫调节剂，如Fingolimod及其后续药物靶向S1P受体用于多发性硬化症。抗肿瘤药物：首个GPCR在癌症中作用的描述可追溯到1986年MAS癌基因的发现。近期，靶向SMO受体的药物获批用于急性髓系白血病和基底细胞癌，靶向CCR4的抗体Mogamulizumab获批用于蕈样肉芽肿或Sézary综合征。Talquetamab作为一种双特异性GPRC5D-CD3 T细胞接合剂，于2023年获批用于多发性骨髓瘤。 -08- 七、未开发的靶点与偏向信号 1. 未开发靶点的潜力尽管GPCR是最重要的药物靶标家族之一，但其非感官受体中仅有三分之一被临床靶向。通过关联文献数据、配体数据和结构数据，研究人员评估了不同靶点的开发状态。分析显示，一些未靶向受体（如CCR7、MCH1、Neuropeptide S受体）拥有丰富的公共数据，可能是潜在的新兴靶点。例如，CCR7有超过300篇出版物，可能在癌症中作为靶点。 2. 未靶向的GPCR-疾病对通过整合Open Targets平台的疾病关联评分，研究发现有50个非感官GPCR与84种疾病相关。其中，发育异常（26种疾病）和内分泌/营养/代谢疾病（18种疾病）领域的疾病数量最多。钙敏感受体具有最多的未靶向疾病关联（6种），TSH受体则关联5种未靶向疾病。此外，整个粘附受体类（B2类）和Frizzled受体类的大多数成员仍处于未靶向状态。 3. 偏向信号 “偏向配体”能够差异性地激活GPCR信号传导的细胞内转导蛋白（如G蛋白和β-抑制蛋白）。偏向信号在设计具有更好疗效和安全性的药物方面具有巨大潜力，因为它可以优先激活治疗有益的信号通路，同时避免引起不良反应的通路。例如，BnOCPA通过腺苷A1受体产生偏向性激活，在不引起心肺抑制的情况下发挥镇痛作用。首个被设计为偏向激动剂的获批药物是Oliceridine，一种μ-阿片受体配体。然而，偏向信号的临床转化仍面临挑战，如体外结果向临床概况改善的转化有限，以及参考配体的选择问题。 -09- 结语 GPCR作为药物靶标家族的重要性毋庸置疑。分析表明，GPCR在未来的药物开发中将继续发挥重要作用，这得益于临床试验中大量的药物、不断增长的适应症格局、未开发的疾病关联以及近期公布的公司合作伙伴关系。考虑到临床试验中生物制剂比例的翻倍（从13%增至29%）和变构调节剂比例的八倍增长（从1%增至8%），这些新型药物形式将为下一代GPCR靶向药物做出重要贡献。同时，药物再利用也占据了临床试验药物的近一半，表明这也是未来GPCR疗法的重要来源。参考文献： GPCR drug discovery: new agents, targets and indications. Nat Rev Drug Discov. 2025 Jun;24(6):458-479. 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。

2026-03-26

·GlobeNewswire-Health Care

Tonix Pharmaceuticals Announces First Participant Dosed in Phase 1 Investigator-Initiated Pharmacodynamic Study of TNX-1900 (Intranasal Potentiated Oxytocin) to Assess Potential for Treating Migraine and Craniofacial Pain

Intranasal oxytocin blocks the release of calcitonin gene-related peptide (CGRP) in animal models and is the core technology of TNX-1900 for craniofacial pain conditions, including migraine and trigeminal neuralgia TNX-1900 will be studied in the trigeminal neurovascular reactivity model, by measuring the forehead skin blood flow response to capsaicin and electrical stimulation by Laser Speckle Contrast Imaging (LSCI) Oxytocin treatment affects a pathway distinct from the recently available CGRP migraine treatment drug class BERKELEY HEIGHTS, N.J., March 26, 2026 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a fully integrated, commercial biotechnology company, today announced that the first participant has been dosed in a Phase 1 investigator-initiated study to evaluate the effect of TNX-1900 (intranasal potentiated oxytocin) on trigeminal nerve-mediated vasodilation of the forehead using capsaicin as well as electrical stimulation, a model for trigeminal neurovascular reactivity, in healthy female human volunteers. Dr. Antoinette Maassen van den Brink, Professor of Neurovascular Pharmacology, Erasmus University Medical Center, is serving as principal investigator and sponsor for the study in a collaborative research agreement with Tonix. In animal studies, intranasal oxytocin has been shown to bind to oxytocin receptors in the trigeminal ganglion, blocking the release of calcitonin gene-related peptide (CGRP), a potent vasodilator critically involved in the pathogenesis of migraine.1 Dr. Maassen van den Brink has previously found a CGRP inhibitor and a triptan to inhibit the forehead dermal blood flow response to capsaicin in migraineurs and healthy volunteers, respectively.2,3 “We are excited to collaborate with Professor Maassen van den Brink on this proof-of-concept study investigating the potential for TNX-1900 for treating migraine, craniofacial pain, and other related conditions,” said Seth Lederman, MD, Chief Executive Officer of Tonix Pharmaceuticals. “While there are several CGRP inhibitors approved for the treatment of migraine, TNX-1900’s oxytocin treatment affects a distinct pathway that could address unmet needs. The results of the new study will guide future development of this potential non-opioid treatment for migraine and other craniofacial pain conditions.” As part of the preliminary work in support of this study, Dr. Maassen van den Brink’s team recently validated a newer detection method for dermal blood flow known as Laser Speckle Contrast Imaging (LSCI) in the trigeminal neurovascular reactivity model.4 “We are excited to be using LSCI in this study of TNX-1900, which adds to our established model by providing real-time and higher resolution dermal blood flow measurements, compared to Laser Doppler Perfusion Imaging used in earlier studies,” said Dr. Maassen van den Brink. “Oxytocin represents a potential new therapeutic option, targeting a pathway in migraine and craniofacial pain that is distinct from both the triptan and CGRP inhibitor migraine treatment drug classes.” About Migraine Migraine is a neurovascular condition that typically manifests in a throbbing moderate to severe headache which lasts at least four hours, often on one side of the head and aggravated by routine physical activity. It can also be accompanied by nausea, vomiting, visual disturbances, and sensitivity to bright light and loud noises.5 Epidemiological studies indicate that globally, approximately 1.2 billion individuals suffer from migraines annually.6 In the U.S., approximately 39 million Americans suffer from migraines, and among these individuals, approximately four million experience chronic migraines (15 or more headache days per month, at least eight of which are migraines).6 About TNX-1900 TNX-1900 (intranasal potentiated oxytocin) is a proprietary formulation of oxytocin in development as a candidate for the treatment of migraine and craniofacial pain. TNX-1900 is a drug-device combination product, based on an intranasal actuator device that delivers oxytocin into the nasal cavity. Oxytocin is a naturally occurring human peptide hormone that also acts as a neurotransmitter in the brain. Oxytocin has no recognized addiction potential. Oxytocin when delivered via the nasal route, concentrates in the trigeminal system7 resulting in binding of oxytocin to receptors on neurons in the trigeminal system, inhibiting the release of CGRP and transmission of pain signals returning from the site of CGRP release.1 Blocking CGRP release is a distinct mechanism compared with CGRP receptor antagonist and anti-CGRP antibody drugs, which block the binding of CGRP to its receptor, or bind to the peptide CGRP. The addition of magnesium to the oxytocin formulation in TNX-1900 enhances oxytocin receptor binding8 as well as having an inhibitory effect on trigeminal neurons and resultant craniofacial analgesic effects, as demonstrated in animal models.9 Intranasal oxytocin has been shown to be well tolerated in several clinical trials in both adults and children.10 Targeted nasal delivery results in low systemic exposure and lower risk of non-nervous system, off-target effects, which could potentially occur with systemic CGRP receptor antagonists and anti-CGRP (receptor) antibodies.11 For example, CGRP has roles in dilating blood vessels in response to ischemia, including in the heart. The Company believes nasally targeted delivery of oxytocin could translate into selective blockade of CGRP release from neurons in the trigeminal ganglion and not throughout the body, which could be a potential safety advantage over systemic CGRP inhibition. This mechanism is being investigated in a Phase 1 study to evaluate the effect of TNX-1900 on trigeminal nerve-mediated vasodilation of the forehead model for craniofacial pain. In addition, daily dosing is more rapidly reversible, in contrast to monthly or quarterly dosing, as is the case with anti-CGRP antibodies, giving physicians and their patients greater control. In addition to craniofacial pain conditions, TNX-1900 is being developed for treatment of binge eating disorder, adolescent obesity, bone health in pediatric autism and arginine-vasopressin deficiency. Tonix also has a license with the University of Geneva to use TNX-1900 for the treatment of insulin resistance and related conditions. Citations 1Tzabazis A, et al. Oxytocin receptor: Expression in the trigeminal nociceptive system and potential role in the treatment of headache disorders. Cephalalgia. 2016. 36(10):943-50.2de Vries Lentsch S, et al. CGRP-mediated trigeminovascular reactivity in migraine patients treated with erenumab. J Neurol Neurosurg Psychiatry. 2022 Aug;93(8):911-912.3Ibrahimi K, et al. A human trigeminovascular biomarker for antimigraine drugs: A randomized double-blind, placebo-controlled, crossover trial with sumatriptan. Cephalalgia. 2017 Jan;37(1):94-98.4van Lohuizen et al. 2025. Trigeminovascular activity using a forehead dermal blood flow model: preliminary results of a validation study. J Headache and Pain 26 (Suppl 2): 138.5The International Classification of Headache Disorders, 3rd Edition. Cephalalgia. 2018. 38(1):1-211.6Burch et al. Migraine: Epidemiology, Burden, and Comorbidity. Neurol Clin 37 (2019):631–649.7Yeomans DC, et al. Nasal oxytocin for the treatment of psychiatric disorders and pain: achieving meaningful brain concentrations. Transl Psychiatry. 2021. 11(1):388.8Antoni FA and Chadio SE. Essential role of magnesium in oxytocin-receptor affinity and ligand specificity. Biochem J. 1989. 257(2):611-4.9Cai Q, et al. Systematic review and meta-analysis of reported adverse events of long-term intranasal oxytocin treatment for autism spectrum disorder. Psychiatry Clin Neurosci. 2018. 72(3):140-151.10Yeomans, DC et al. 2017. US patent US2017368095.11MaassenVanDenBrink A, et al. Wiping out CGRP: potential cardiovascular risks. Trends Pharmacol Sci. 2016. 37(9):779-788. Tonix Pharmaceuticals Holding Corp. Tonix Pharmaceuticals* is a fully-integrated, commercial-stage biotechnology company focused on central nervous system (CNS) and immunology treatments in areas of high unmet medical need. TONMYA® (cyclobenzaprine HCl sublingual tablets 2.8 mg), is the first new treatment for fibromyalgia in adults in more than 15 years. Tonix’s CNS commercial infrastructure supports its marketed products, including its acute migraine products, Zembrace® Symtouch® (sumatriptan injection 3 mg) and Tosymra® (sumatriptan nasal spray 10 mg). Tonix is investigating TONMYA® in Phase 2 clinical trials to evaluate its potential in major depressive disorder and acute stress disorder/acute stress reaction. In addition, the Company’s CNS portfolio includes TNX-2900 (intranasal oxytocin), which is Phase 2 ready for the treatment of Prader-Willi syndrome, a rare disease. Tonix is also advancing a pipeline of immunology programs, including long-acting human monoclonal antibody TNX-4800 for Lyme disease prophylaxis, and TNX-1500, a third-generation CD40 ligand inhibitor for the prevention of kidney transplant rejection. To learn more, visit www.tonixpharma.com and follow the Company on LinkedIn and X. *Tonix’s product development candidates are investigational new drugs or biologics; their efficacy and safety have not been established and have not been approved for any indication. Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. TONMYA is a registered trademark of Tonix Pharma Limited. All other marks are property of their respective owners. Forward Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995 including those relating to the completion of the offering, the satisfaction of customary closing conditions, the intended use of proceeds from the offering and other statements that are predictive in nature. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to successfully launch and commercialize TONMYA and any of our approved products; risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Company’s Annual Report on Form 10-K for the year ended December 31, 2025, as filed with the SEC on March 12, 2026, and periodic reports filed with the SEC on or after the date thereof. Tonix does not undertake an obligation to update or revise any forward-looking statement. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof. Investor ContactsJessica MorrisTonix Pharmaceuticalsinvestor.relations@tonixpharma.com (862) 799-8599 Brian Korbastr partners(917) 653-5122brian.korb@astrpartners.com Media ContactsDeborah ElsonTonix Pharmaceuticalsdeborah.elson@tonixpharmaceuticals.com Ray JordanPutnam Insightsray@putnaminsights.com

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100 项与依瑞奈尤单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	依瑞奈尤单抗	N02CD01	DB14039

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
偏头痛	美国	Amgen, Inc.	2018-05-17

未上市

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适应症	最高研发状态	国家/地区	公司	日期
神经痛	临床2期	美国	Amgen, Inc.	2022-05-31
三叉神经疾病	临床2期	美国	Amgen, Inc.	2022-05-31
三叉神经损伤	临床2期	美国	Amgen, Inc.	2022-05-31
三叉神经痛	临床2期	美国	Amgen, Inc.	2022-05-31
颞下颌关节障碍	临床2期	美国	Amgen, Inc.	2021-11-15
皮肤潮红	临床2期	丹麦	Novartis Pharmaceuticals Corp.	2020-06-09
玫瑰痤疮	临床2期	丹麦	Novartis Pharmaceuticals Corp.	2020-06-09
头痛	临床2期	丹麦	Novartis AG	2019-04-05
头痛	临床2期	丹麦	Amgen, Inc.	2019-04-05
脑震荡后综合征	临床2期	丹麦	Amgen, Inc.	2019-04-05

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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


NCT03333109 (EMPOwER, Pubmed \| Neurol Clin Pract)	临床3期	偏头痛	900	Erenumab 140 mg	繭齋艱衊鑰蓋淵範憲顧(醖憲遞選糧觸構鹹糧襯) = 積選艱窪鹹鹹繭願襯醖齋衊艱壓衊憲構憲蓋窪 (簾遞廠糧鑰製觸壓衊膚 ) 更多	积极	2026-04-01
				Erenumab 70 mg	繭齋艱衊鑰蓋淵範憲顧(醖憲遞選糧觸構鹹糧襯) = 網鏇糧糧鏇鏇鹹選艱獵齋衊艱壓衊憲構憲蓋窪 (簾遞廠糧鑰製觸壓衊膚 ) 更多
NCT04098250 (CTgov)	临床2期	创伤后头痛	6	Erenumab (Erenumab)	齋膚製遞夢網淵網窪獵(遞製糧願網願範憲膚鑰) = 壓鬱鹽獵艱壓鹽簾壓繭範窪願廠壓鹹選醖構膚 (糧觸齋願衊壓簾齋廠網, 2.8) 更多	-	2025-10-23
				Placebo (Placebo)	齋膚製遞夢網淵網窪獵(遞製糧願網願範憲膚鑰) = 衊鑰鑰選獵鏇選壓構膚範窪願廠壓鹹選醖構膚 (糧觸齋願衊壓簾齋廠網, 6.0) 更多
NCT04884763 (CTgov)	临床2期	颞下颌关节障碍	30	Erenumab-aooe (Arm A)	廠繭築窪鏇窪艱窪餘簾(鹹夢願醖夢觸簾餘獵觸) = 遞遞觸憲餘構艱淵壓鹽築遞齋鬱願膚廠製憲遞 (醖選憲蓋簾鏇築壓壓簾, 醖窪鑰獵鹹糧襯艱繭簾 ~ 遞製鏇糧範膚範製糧範) 更多	-	2025-08-19
				Placebo (EREN-P) s.c. administered every four weeks for a total of five treatments (Arm B)	廠繭築窪鏇窪艱窪餘簾(鹹夢願醖夢觸簾餘獵觸) = 繭淵夢膚簾鏇糧網糧餘築遞齋鬱願膚廠製憲遞 (醖選憲蓋簾鏇築壓壓簾, 廠築簾淵鏇鬱夢壓遞廠 ~ 鏇醖衊遞鏇積衊鏇醖衊) 更多
NCT03971071 (Pubmed \| Eur J Neurol)	临床4期	继发性头痛症	552	Erenumab 70 mg	窪遞遞簾淵獵糧製艱顧(糧齋願廠繭鑰鑰築鹹願) = No new safety concerns were identified (grade ≥ 3, 35 [6.3%]; serious, 17 [3.1%]; adverse events leading to treatment discontinuation, 5 [0.9%]) 壓遞壓齋壓積願繭構壓 (窪夢醖網窪觸網膚廠觸 )	积极	2025-08-01
				Erenumab 140 mg
NCT04970355 (CHERUB01, Pubmed \| JAMA Netw Open)	临床2期	丛集性头痛 CGRP	81	Erenumab	範衊築廠齋鹽鬱顧網範(壓選廠窪醖艱憲醖鑰蓋) = 窪繭鑰襯蓋蓋餘蓋網簾簾構餘繭窪廠醖醖壓窪 (淵鹹網獵選網鬱鹹鏇衊 )	不佳	2025-06-17
				Placebo	範衊築廠齋鹽鬱顧網範(壓選廠窪醖艱憲醖鑰蓋) = 艱鬱醖積鬱範遞艱蓋鏇簾構餘繭窪廠醖醖壓窪 (淵鹹網獵選網鬱鹹鏇衊 )
NCT04674020 \| NCT04603976 (REFORM study, Pubmed \| J Headache Pain)	临床4期	偏头痛 soluble urokinase-plasminogen activator receptor (suPAR)	623	Erenumab 140 mg	窪顧壓廠衊醖艱淵衊餘(獵醖願簾憲糧淵衊積膚): P-Value = 0.005	不佳	2025-04-24
				erenumab (Healthy Controls)
NCT04084314 (APOLLON, Pubmed \| J Headache Pain) 人工标引	临床4期	偏头痛	701	Erenumab 70 mg	獵網鏇鹹鬱構築構窪鑰(鬱窪艱鬱願觸夢蓋願築) = 4.1% of total cohort discontinued erenumab treatment during open-label treatment phase. Out of these, 65.5% (N = 19) were considered treatment-related. 築繭糧鬱餘鏇膚窪廠鑰 (廠憲鑰窪繭選醖鹽襯鹹 )	积极	2024-09-25
				Erenumab 140 mg
NCT04825678 (CTgov)	临床4期	偏头痛	240	Erenumab (Erenumab QM: Continued SoC)	鏇觸願窪餘糧願鏇鹽淵(夢鬱獵構範積鏇簾積鏇) = 夢蓋蓋鏇築衊齋窪遞範蓋範衊網積艱憲糧醖願 (獵餘夢餘積製夢夢蓋鏇, 32.48) 更多	-	2024-09-19
				Erenumab (Erenumab QM: Discontinued SoC)	鏇觸願窪餘糧願鏇鹽淵(夢鬱獵構範積鏇簾積鏇) = 廠淵簾鹽餘繭齋鏇顧壓蓋範衊網積艱憲糧醖願 (獵餘夢餘積製夢夢蓋鏇, 57.66) 更多
NCT03971071 (Pubmed \| JAMA Neurol) 人工标引	临床4期	偏头痛	620	Erenumab 70 mg	廠築鏇衊憲願鹹膚築網(觸選壓餘鏇顧築鏇襯簾) = 糧鹹鑰衊構鬱醖餘範鏇糧觸築鏇窪選製艱鑰廠 (糧醖製鏇鏇齋繭廠網構 ) 更多	积极	2024-09-16
				Erenumab 140 mg	廠築鏇衊憲願鹹膚築網(觸選壓餘鏇顧築鏇襯簾) = 淵窪築鑰壓醖膚鏇繭鹹糧觸築鏇窪選製艱鑰廠 (糧醖製鏇鏇齋繭廠網構 ) 更多
NCT04252742 (EMBRACE, CTgov)	临床4期	偏头痛 \| 急性偏头痛 \| 无先兆偏头痛	512	Placebo	壓餘選膚鏇範夢衊醖膚(鏇齋鑰鹹餘淵艱獵網繭) = 獵憲簾繭齋積築艱築簾鏇選醖醖醖願繭選鹹壓 (鑰觸壓鑰獵廠觸築鹹願, 1.26) 更多	-	2024-08-30