Real-life effectiveness of Indacaterol/Glycopyrronium/Mometasone for symptomatic relief of cough after switching from ICS/LABA therapy in patients with asthma

开始日期2022-10-12

申办/合作机构

Novartis Pharma KK

CTRI/2021/12/038978

/ Not yet recruitingN/A

An International, Open, Randomized, Comparative study of the efficacy and safety of the medicinal products Glycopyrronium bromide plus Indacaterol 50 plus 110 Î¼g inhalation powder capsules (PSK Pharma LLC, Russia) and Ultibro Breezhaler 50 plus 110Î¼g inhalation powder capsules(Novartis Pharma AG, Switzerland) in subjects with COPD

开始日期2021-12-31

申办/合作机构-

CTRI/2021/10/037155

/ Completed临床3期

A prospective, randomized, double blind, parallel, multicentre, phase III clinical trial to assess the efficacy and safety of Indacaterol and Budesonide Inhalation as compared to Formoterol Fumarate and Budesonide Inhalation in patients with Chronic Obstructive Pulmonary Disease.

开始日期2021-10-18

申办/合作机构

Zydus Healthcare Ltd.

100 项与醋酸茚达特罗相关的临床结果

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100 项与醋酸茚达特罗相关的转化医学

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100 项与醋酸茚达特罗相关的专利（医药）

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项与醋酸茚达特罗相关的文献（医药）

2025-11-01·The journal of allergy and clinical immunology. Global

Effectiveness of indacaterol/glycopyrronium/mometasone for refractory asthmatic cough after switching from inhaled corticosteroid/long-acting β2-agonist therapy

Article

作者: Saito, Junpei ; Miyao, Naoki ; Kamei, Tadashi ; Ohbayashi, Hiroyuki ; Tochigi, Takao ; Yamagata, Eiji ; Matsuoka, Hirofumi ; Tajiri, Tomoko ; Kiyosue, Arihiro ; Mikami, Toshiaki ; Tsuji, Toshinaga ; Fukushima, Yasushi ; Kanemitsu, Yoshihiro ; Niimi, Akio ; Asamoto, Hitoshi ; Hara, Johsuke

Background:

Cough is a major symptom in poorly or partially controlled asthma, which persists despite treatment, thus impairing quality of life.

Objectives:

The primary objective was to demonstrate the superiority of medium-dose indacaterol, glycopyrronium, and mometasone furoate (IND/GLY/MF) over high-dose inhaled corticosteroids (ICS)/long-acting β₂-agonists (LABA) in adult asthma patients with cough refractory to medium-dose ICS/LABA.

Methods:

In this multicenter, randomized, open-label, parallel-group study, 118 patients were randomized to receive either IND/GLY/MF or high-dose ICS/LABA (fluticasone/vilanterol [FF/VI] or budesonide/formoterol [BUD/FM]) for 8 weeks. Efficacy was measured by the Japanese version of the Leicester Cough Questionnaire at week 8. Additional analyses included a visual analog scale, the 6-item Asthma Control Questionnaire, respiratory function, fractional exhaled nitric oxide, and blood eosinophil/neutrophil measurements. Registration: Public clinical trials registry as study jRCTs04122000.

Results:

The change from baseline to week 8 in the total questionnaire score was 1.99 ± 3.48 in the IND/GLY/MF group and 2.50 ± 4.28 in the high-dose ICS/LABA group, with no statistically significant difference between the two groups (P = .5037). However, the change in the total questionnaire score from baseline to week 8 was statistically significant in each treatment group (P < .0001 in the IND/GLY/MF group, P = .0242 in the FF/VI comparator group, and P = .0012 in the BUD/FM comparator group). Fractional exhaled nitric oxide and eosinophil counts significantly decreased in the high-dose ICS/LABA group, while neutrophil counts significantly fell in the IND/GLY/MF group at week 8, by between-group comparison.

Conclusion:

Symptoms improved comparably between medium-dose IND/GLY/MF and high-dose ICS/LABA combinations, although no superiority could be demonstrated. Medium-dose IND/GLY/MF may be an alternative to high-dose ICS/LABA.

2025-10-21·MINI-REVIEWS IN MEDICINAL CHEMISTRY

COPD Treatment with Beta 2-Adrenoreceptor Agonists: Medicinal Perspectives and Recent Advances

Article

作者: Singh, Hridayanand ; Rastogi, Sameer ; Sharma, Shalini ; Rana, Neha

Abstract::

Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition defined by persistent bronchitis, emphysema, and structural remodelling. The number of cases has risen globally; however, limited viable remedies exist. It is linked to airway blockage, oxidative stress, chronic conditions, inflammation, excessive mucus production, and increased autophagy and cellular senescence. Beta-2 adrenergic receptors (β2-ARs) play a significant role in both the aetiology and management of COPD. Beta-2 agonists (particularly long-acting beta-agonists, or LABAs) are preferable in COPD therapy due to their powerful bronchodilation, rapid onset, prolonged duration, and potential synergistic effects with other medications. They are well-tolerated and effective in improving the quality of life and reducing exacerbations, making them an essential component of COPD treatment. Currently, there are fewer bronchodilators that have been found to be effective. This leads to an exploration of novel, long-acting, and ultra-long-acting drugs for the management of COPD. This article provides an extensive overview of natural β2 agonists. The current study emphasizes the rational development of lead candidates, including trantinterol, isopropyl, tert-butyl, and heterocyclic ring 2-amino-2-phenylethanol derivatives, 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4- benzoxazine-3(4H)-one derivatives (non-substituted, methyl-substituted, dimethyl-substituted), 5- (2-amino-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one analogues, indacaterol analogues, saligenin antedrugs, and saligenin alkoxyalkylphenyl sulfonamide derivatives, accompanied by molecular docking studies.This paper also highlights numerous structure-activity relationship investigations and various novel β2 agonists currently in clinical trials and patents. The present review will significantly aid in fostering the research of COPD.

2025-10-01·Journal of Thoracic Disease

Efficacy, pharmacokinetics, and safety of nebulized HL231 inhalation solution in patients with chronic obstructive pulmonary disease: a randomized trial

Article

作者: Bian, Tao ; Xiong, Hao ; Li, Fangqiong ; Yue, Yun ; Xie, Lihua ; Li, Yaming ; Xiao, Zuke ; Hu, Qingyuan ; Yang, Guoping ; Zhao, Li ; Chen, Feng ; Wen, Fuqiang ; Luo, Zhu ; He, Qing ; Luo, Lin

Background:

Long-acting beta-agonist (LABA) plus long-acting muscarinic antagonist (LAMA) is superior to monotherapy or corticosteroid/LABA in terms of improving lung function, alleviating symptoms and educe chronic obstructive pulmonary disease (COPD) exacerbations. This study aimed to establish optimal dosage of nebulized HL231 inhalation solution (HL231), comparable to Ultibro^® (110 µg indacaterol maleate/50 µg glycopyrronium bromide), for bronchodilatation, pharmacokinetics, and safety in COPD.

Methods:

This study employed a multicenter, randomized, single-dose, single-blind, crossover design and featured two parts. The randomization schedule was generated by the statistical team using the block randomization procedure in SAS software. Chinese adults aged 40 years or older who were diagnosed with moderate-to-severe COPD using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria were eligible for the study. Blinding was implemented for the personnel conducting pulmonary function tests. In Part A, patients were randomized to receive a single dose of HL231 (132 µg/72 µg, 261 µg/141 µg, or 516 µg/279 µg), Ultibro^®, or placebo in a randomized sequence with a washout period of at least 14 days between two visits. The primary efficacy endpoint was the change in the area under the curve (AUC) of FEV₁ from baseline to 12 h after administration (ΔFEV₁ AUC_0-12h). In Part B, patients were randomized to receive a single dose of HL231 (261 µg/120 µg and 261 µg/141 µg), or Ultibro^® in a randomized sequence. The primary endpoints were pharmacokinetic parameters, including the AUC from time 0 to the last detectable time point (AUC_0-t), AUC from time 0 to infinity (AUC_0-∞), and peak concentration (C_max). Safety was evaluated in both parts.

Results:

The study was initiated and completed between December 2021 and May 2023, with 173 and 29 patients screened in Part A and Part B respectively, resulting in 84 and 18 randomized patients, of whom 83 and 18 completed at least one treatment cycle. In Part A, the least squares (LS) mean differences in ΔFEV₁ AUC_0-12h for HL231 doses (132 µg/72 µg, 261 µg/141 µg, and 516 µg/279 µg) and Ultibro^® versus placebo were 2.30, 2.58, 2.68, and 2.33 L·h (all P<0.001), respectively, while compared to Ultibro^®, differences were -0.04 (P=0.83), 0.24 (P=0.14), and 0.35 L·h (P=0.04), respectively. Moreover, the LS means of ΔFEV₁ AUC0-12h for these doses were 2.30, 2.58, and 2.69 L·h, indicating a dose-response relationship. In Part B, HL231 261 µg/141 µg demonstrated peak concentration (C_max) of indacaterol and glycopyrronium at 86% and 54% of Ultibro^®, with comparable AUC_0-t. Safety was acceptable, with most treatment-emergent adverse events (TEAEs) being grade 1-2.

Conclusions:

HL231 (261 µg/141 µg) is highly comparable to Ultibro^® in bronchodilatation, pharmacokinetics, and safety, making it a potential alternative for COPD patients.

Trial Registration:

This study was registered at Chinese Clinical Trials Registration (ChiCTR2300068316) and clinicaltrials.gov (NCT06619210, retrospectively registered).

项与醋酸茚达特罗相关的新闻（医药）

2025-10-23

·有驾

慢性阻塞性肺疾病新型吸入制剂的研发进展：聚焦用药依从性改善与治疗效果提升

慢性阻塞性肺疾病（COPD）是全球第三大死亡原因，吸入制剂因 “直接作用于靶器官、全身副作用少” 成为一线治疗手段，但传统吸入制剂（如短效单一制剂、复杂装置干粉吸入剂）存在用药依从性差（全球平均依从率＜50%）、肺部沉积率低（仅 10%-20%）、急性加重控制不足等局限，导致临床疗效未达预期。近年新型吸入制剂通过 “制剂设计革新 + 装置技术升级”，从 “长效化、复方化、智能化、靶向化” 四大方向突破，显著改善患者依从性与治疗结局。本文系统综述 COPD 新型吸入制剂的核心研发方向：①长效复方吸入制剂（LABA/LAMA、LABA/LAMA/ICS 三联制剂）通过减少给药频率、整合多靶点治疗提升依从性；②超细颗粒吸入制剂通过优化粒径（1-3 μm）提高肺部沉积率，增强疗效并降低全身副作用；③智能吸入装置结合传感器与 APP 实现用药监测与提醒，解决 “遗忘用药”“操作错误” 问题；④干粉吸入剂（DPI）改良与靶向递送制剂（如黏液溶解型、细胞靶向型）适配特殊人群（老年、重度 COPD 患者）并提升病变区域药物浓度。基于近年 Ⅲ 期临床试验数据（如 IMPACT、ETHOS 试验），从肺功能（FEV₁）、急性加重率、CAT 评分、用药依从率等维度评估疗效与依从性改善效果；最后指出当前研发存在的生产成本高、装置适配性不足、长期安全性数据缺乏等挑战，并展望 “个性化制剂”“生物制剂吸入化”“可降解装置” 等未来方向，为 COPD 吸入治疗的临床转化与规范应用提供循证依据。引言 COPD 以 “持续气流受限、气道慢性炎症、肺功能进行性下降” 为核心特征，2025 年全球患病人数预计超 3.8 亿，每年因急性加重导致的住院率达 15%-20%，死亡风险较稳定期升高 3-5 倍。吸入给药是 COPD 治疗的 “金标准”，其优势在于：药物直接作用于气道和肺部靶器官，局部药物浓度高（是口服制剂的 5-10 倍），全身暴露量低（全身副作用发生率＜5%），但传统吸入制剂的临床应用面临三大核心痛点：用药依从性极差：COPD 患者多为老年人群（≥60 岁），合并认知功能下降、手部协调能力减弱，传统装置（如压力定量气雾剂 pMDI 需同步按压与吸气，干粉吸入剂 DPI 需快速深吸气）的操作错误率达 40%-60%；且传统制剂多为 “短效单一成分”（如沙丁胺醇 pMDI，每日给药 3-4 次），患者遗忘用药率超 50%，最终导致规范治疗率不足 30%。肺部沉积效率低：传统吸入制剂的药物颗粒粒径多为 5-10 μm，仅 10%-20% 能沉积于小气道（直径＜2 mm）和肺泡区域，其余颗粒因惯性撞击沉积于口咽部（易引发声音嘶哑、口腔念珠菌感染）或随呼气排出，导致 “有效剂量不足”，FEV₁改善幅度仅为预期的 60%-70%。急性加重控制不足：COPD 急性加重（AECOPD）的核心诱因是气道炎症加剧与黏液高分泌，传统单一制剂（如仅含支气管扩张剂的 LABA）无法同时抗炎与改善黏液清除，导致患者每年急性加重次数达 1.5-2.5 次，严重影响生活质量与生存期。新型吸入制剂的研发以 “解决上述痛点” 为核心，通过制剂配方优化与装置技术创新，实现 “减少给药频率、提升肺部沉积、智能监测用药”，为 COPD 患者提供更高效、便捷的治疗方案。本文聚焦这些新型制剂的研发逻辑、临床证据与应用前景，为医学专业人士提供参考。一、COPD 新型吸入制剂的核心研发方向与技术突破（一）长效复方吸入制剂：从 “单药多次” 到 “多药一次”，提升依从性与疗效协同 COPD 的治疗需同时覆盖 “支气管扩张（缓解气流受限）、抗炎（控制气道炎症）、黏液调节（改善排痰）” 三大靶点，传统单药或短效复方制剂需多次给药，而长效复方制剂通过 “多靶点药物整合 + 延长作用时间”，实现 “每日 1 次给药”，显著降低用药负担，是当前研发的主流方向。 1. 双联长效复方制剂（LABA/LAMA）研发逻辑：LABA（长效 β₂受体激动剂，如茚达特罗、维兰特罗）通过激动 β₂受体舒张气道平滑肌，作用持续 12-24 小时；LAMA（长效抗胆碱能药物，如格隆溴铵、乌美溴铵）通过阻断 M₃受体抑制气道收缩，两者协同增强支气管扩张效果，且无明显副作用叠加。技术突破：采用 “共悬浮技术” 或 “脂质体包埋” 实现药物同步释放，避免单一成分提前失效。例如，茚达特罗 / 格隆溴铵干粉吸入剂（Ultibro® Breezhaler）通过 “超细颗粒共混”，使两种药物的肺部沉积率均达 25%-30%（传统单药 DPI 沉积率 15%-20%），且作用持续 24 小时，支持每日 1 次给药。临床证据：Ⅲ 期试验（TONADO 1/2）显示，COPD 患者使用茚达特罗 / 格隆溴铵（110/50 μg qd）治疗 24 周，FEV₁谷值较基线提升 156-187 mL，显著高于单药 LABA（102 mL）或 LAMA（98 mL）；急性加重率较安慰剂降低 31%，用药依从率达 72%（传统短效复方制剂依从率 45%）。 2. 三联长效复方制剂（LABA/LAMA/ICS）研发逻辑：在 LABA/LAMA 基础上加入 ICS（吸入性糖皮质激素，如糠酸氟替卡松、布地奈德），针对 COPD 患者的气道慢性炎症（嗜酸性粒细胞浸润），尤其适合 “频繁急性加重（每年≥2 次）、血嗜酸性粒细胞≥300/μL” 的患者，实现 “扩张气道 + 抗炎” 双重作用，减少急性加重风险。技术突破：采用 “压力定量气雾剂（pMDI）超细颗粒配方” 或 “干粉吸入剂多室储药设计”，确保三种药物同步均匀释放，肺部沉积率均达 20%-25%，且 ICS 的全身吸收量降低（血药浓度＜100 pg/mL），减少骨质疏松、血糖升高风险。临床证据：关键 Ⅲ 期试验（IMPACT）纳入 10355 例中重度 COPD 患者，对比糠酸氟替卡松 / 乌美溴铵 / 维兰特罗（FF/UMEC/VI，100/62.5/25 μg qd）与双联制剂（FF/VI、UMEC/VI）的疗效：FF/UMEC/VI 组 FEV₁谷值提升 181 mL，显著高于双联组（143-150 mL）；急性加重率较 FF/VI 组降低 15%，较 UMEC/VI 组降低 26%；用药依从率达 78%，因副作用停药率仅 5.2%（传统三联制剂停药率 8.5%）。（二）超细颗粒吸入制剂：提升肺部沉积率，增强疗效并减少副作用传统吸入制剂的药物颗粒粒径多为 5-10 μm，易沉积于口咽部，而超细颗粒制剂（粒径 1-3 μm）可随气流深入小气道（直径＜2 mm）和肺泡区域，肺部沉积率提升至 30%-40%，同时减少口咽部沉积导致的局部副作用（如声音嘶哑、口腔念珠菌感染发生率从 10%-15% 降至 3%-5%）。 1. 超细颗粒干粉吸入剂（DPI）技术突破：采用 “喷雾干燥 - 气流粉碎联用技术” 制备超细颗粒，同时添加 “载体表面改性剂”（如硬脂酸镁、卵磷脂），避免颗粒团聚，确保吸入时颗粒均匀分散。例如，超细颗粒茚达特罗 DPI（粒径 2.5 μm）通过 “多孔载体吸附” 技术，肺部沉积率达 38%，是传统茚达特罗 DPI（粒径 6 μm，沉积率 18%）的 2 倍以上。临床优势：针对 “小气道功能障碍为主” 的 COPD 患者（FEV₁/FVC＜70% 且小气道阻力＞2.5 kPa・s/L），超细颗粒制剂可显著改善小气道通气功能 ——Ⅲ 期试验显示，超细颗粒格隆溴铵 DPI 治疗 12 周，患者小气道阻力较基线降低 32%，显著高于传统颗粒组（18%）；CAT 评分（生活质量评估）降低 4.2 分，传统组降低 2.8 分。 2. 超细颗粒压力定量气雾剂（pMDI）技术突破：采用 “氢氟烷烃（HFA）作为抛射剂” 替代传统氟利昂，配合 “微喷嘴设计”（孔径 5-10 μm），使药物颗粒粒径控制在 1-2 μm，且喷射速度降低（＜10 m/s），减少颗粒在咽喉部的惯性撞击。例如，超细颗粒沙丁胺醇 pMDI（ProAir® Digihaler）的肺部沉积率达 35%，是传统沙丁胺醇 pMDI（沉积率 12%）的 2.9 倍。临床优势：适用于 “急性加重期快速缓解”，超细颗粒可快速到达小气道，缓解气流受限 ——Ⅱ 期试验显示，急性加重期患者使用超细颗粒沙丁胺醇 pMDI（100 μg）后，FEV₁在 5 分钟内提升 120 mL，显著快于传统 pMDI（10 分钟提升 90 mL）；且因全身吸收量减少，心悸发生率从 12% 降至 4%。（三）智能吸入装置：解决 “遗忘用药” 与 “操作错误”，提升用药依从性 COPD 患者的用药依从性差，70% 源于 “遗忘用药”（老年患者认知功能下降）和 “操作错误”（装置使用复杂），智能吸入装置通过 “传感器 + 无线通信 + APP” 实现用药监测、提醒与操作指导，是改善依从性的关键技术。 1. 智能干粉吸入装置（DPI）技术配置：内置蓝牙传感器、压力传感器与加速度传感器，可记录 “用药时间、吸入流速、吸入深度”，数据实时同步至患者 / 医护 APP；当患者遗忘用药时，APP 推送提醒（铃声 + 弹窗）；当吸入流速不足（＜30 L/min）或吸入时间过短（＜1 秒）时，装置灯光提示操作错误，并通过 APP 指导正确操作。代表产品：糠酸氟替卡松 / 乌美溴铵 / 维兰特罗智能 DPI（Ellipta® Smart）、茚达特罗 / 格隆溴铵智能 DPI（Breezhaler® Connect）。临床证据：一项多中心研究纳入 520 例老年 COPD 患者（≥65 岁），使用智能 DPI 治疗 6 个月：用药依从率从基线 42% 提升至 81%，操作错误率从 45% 降至 8%；急性加重率较传统 DPI 组降低 28%，CAT 评分降低 5.3 分（传统组降低 3.1 分）。 2. 智能压力定量气雾剂（pMDI）技术配置：在传统 pMDI 基础上加装 “剂量计数器 + 倾斜传感器”，记录每次按压是否与吸气同步（避免 “早按 / 晚按” 导致的药物浪费）；APP 可生成 “用药日历”，医护人员通过后台查看患者用药数据，及时干预不依从行为（如电话提醒、门诊指导）。临床优势：针对 “手部协调能力差” 的患者（如合并类风湿关节炎、脑卒中后遗症），智能 pMDI 的 “吸气 - 按压同步提示” 可使操作成功率从 55% 提升至 92%；一项队列研究显示，使用智能 pMDI 的患者，药物浪费率从 35% 降至 12%，每支药物的实际使用天数从 20 天延长至 28 天。（四）特殊人群适配制剂：针对老年、重度 COPD 患者的剂型改良 1. 易操作干粉吸入剂（DPI）研发逻辑：老年 COPD 患者（≥70 岁）多存在吸气力量不足（吸入流速＜60 L/min），传统 DPI 需高流速（≥60 L/min）才能有效释放药物，而改良型 DPI 通过 “低阻力气道设计”（气道阻力＜0.5 kPa・s/L），使患者在低流速（30-40 L/min）下仍能达到有效肺部沉积率（25%-30%）。代表产品：噻托溴铵低阻力 DPI（Spiriva® Respimat®），采用 “软雾技术” 替代传统干粉，喷射速度慢（0.8 m/s）、雾滴粒径小（2.9 μm），患者无需快速深吸气，只需缓慢平稳吸气即可，操作成功率达 95%（传统 DPI 成功率 62%）。 2. 黏液溶解型吸入制剂研发逻辑：重度 COPD 患者（FEV₁＜50% 预计值）常合并黏液高分泌与气道黏液栓塞，传统吸入制剂难以穿透黏液层到达气道壁，而黏液溶解型制剂通过添加 “黏液溶解剂”（如 N - 乙酰半胱氨酸、氨溴索）或 “渗透促进剂”（如吐温 80），降低黏液黏度（黏度降低 40%-50%），促进药物穿透。临床证据：氨溴索 / 沙丁胺醇复方吸入剂（250/100 μg bid）治疗重度 COPD 患者 12 周，患者痰液排出量较基线增加 60%，FEV₁提升 130 mL，急性加重率较沙丁胺醇单药组降低 33%；且因黏液清除改善，肺部感染发生率从 22% 降至 10%。二、新型吸入制剂的临床疗效与用药依从性评估基于近年 15 项多中心 Ⅲ 期临床试验（累计纳入 38200 例 COPD 患者），从 “疗效指标”“依从性指标”“安全性指标” 三个维度，对比传统与新型吸入制剂的优势，核心数据如下：（一）疗效指标对比（二）用药依从性指标对比用药依从率：新型制剂（长效复方 + 智能装置）的依从率达 72%-81%，显著高于传统制剂（35%-45%，P＜0.001）；其中，智能装置的 “提醒功能” 可使遗忘用药率从 50% 降至 15%，“操作指导” 可使操作错误率从 40% 降至 8%。治疗持续性：新型制剂的 6 个月治疗持续率达 85%-90%，传统制剂为 55%-65%（P＜0.001）；主要原因是新型制剂的给药频率低（每日 1 次 vs 每日 3-4 次）、副作用少（全身副作用发生率 5%-8% vs 10%-15%）。（三）安全性指标局部副作用：超细颗粒制剂的口咽部沉积率低，声音嘶哑发生率 3%-5%（传统制剂 10%-15%），口腔念珠菌感染发生率 2%-4%（传统制剂 8%-12%）。全身副作用：长效复方制剂中 ICS 的剂量优化（如 FF 100 μg/qd），使骨质疏松发生率＜1%（传统 ICS 制剂 2%-3%），血糖升高发生率＜2%（传统制剂 4%-5%）。严重不良事件：新型制剂的严重不良事件发生率（5%-7%）与传统制剂（6%-8%）无显著差异（P＞0.05），主要不良事件为肺炎（发生率 3%-4%），但无证据显示新型制剂增加肺炎风险。三、当前研发挑战与未来展望（一）核心挑战生产成本与可及性：新型吸入制剂（尤其是智能装置与超细颗粒制剂）的生产成本较高（如智能 DPI 的单价是传统 DPI 的 2-3 倍），基层医院与低收入人群的可及性不足；且部分新型制剂依赖进口，国产化率低（仅 30%-40%），进一步推高用药成本。装置适配性与培训不足：虽智能装置简化了操作，但仍有 10%-15% 的老年患者（≥80 岁）因 “不会使用智能手机 APP” 无法享受智能功能；且临床医护人员对新型装置的培训不足，仅 40% 的医院开展系统的吸入装置操作培训，导致部分患者未能掌握正确使用方法。长期安全性数据缺乏：多数新型吸入制剂的临床试验随访周期为 6-12 个月，2 年以上的长期安全性数据（如超细颗粒制剂对肺组织的长期影响、智能装置的电池寿命与数据安全性）不足，限制了其在老年、合并多基础疾病患者中的广泛应用。特殊人群临床证据不足：针对 “极重度 COPD（FEV₁＜30% 预计值）”“合并支气管扩张症”“儿童 COPD” 的新型制剂临床试验较少，此类人群的用药方案仍依赖经验性调整，缺乏循证依据。（二）未来展望个性化吸入制剂研发：基于患者的 “肺功能分型（小气道障碍型 / 肺气肿型）”“炎症表型（嗜酸性粒细胞高 / 低）”“基因多态性（如 β₂受体基因型）”，开发 “定制化制剂”—— 例如，对 β₂受体 Arg16Gly 基因型患者，调整 LABA 剂量（增加 20%）以提升疗效；对小气道障碍型患者，优先使用超细颗粒制剂。生物制剂与吸入制剂的结合：将抗 IL-5、抗 IL-13 等生物制剂制成吸入制剂，直接作用于气道炎症部位，减少全身暴露量（如抗 IL-5 吸入制剂的血药浓度仅为静脉制剂的 1/10），当前临床前研究已显示抗 IL-5 吸入制剂可降低 COPD 患者的嗜酸性粒细胞计数（降低 60%），预计 5-8 年内进入 Ⅰ 期临床试验。可降解智能吸入装置：开发 “可降解聚合物材质” 的智能装置，避免传统塑料装置的环境污染；同时集成 “呼气末 CO₂监测” 功能，实时评估患者通气功能，动态调整用药方案（如通气功能恶化时，APP 提醒医生调整剂量）。真实世界研究与医保政策支持：开展大规模真实世界研究（样本量＞10 万例），评估新型吸入制剂在基层医院、老年人群中的疗效与安全性；推动新型制剂纳入国家医保目录，降低患者自付比例（从当前 50%-60% 降至 20%-30%），提升可及性。 COPD 新型吸入制剂通过 “长效复方化、超细颗粒化、智能装置化、特殊人群适配化” 的研发突破，显著解决了传统制剂 “依从性差、肺部沉积率低、急性加重控制不足” 的痛点 —— 长效复方制剂实现 “每日 1 次给药”，智能装置将依从率提升至 72%-81%，超细颗粒制剂使肺部沉积率达 30%-40%，临床数据显示 FEV₁改善幅度提升 50%-80%，急性加重率降低 26%-33%。当前需通过 “降低生产成本、加强医护培训、积累长期安全性数据” 推动临床转化，未来个性化制剂与生物制剂吸入化的发展，将进一步实现 COPD 的 “精准治疗”，为患者带来 “更好疗效、更低负担、更高生活质量” 的治疗结局。

临床3期临床结果

2025-10-07

·Business Wire

AeroRx Therapeutics Announces $21 Million Series A Financing to Advance Inhaled AERO-007, the First Nebulized LABA/LAMA for COPD, into Late-Stage Clinical Development

LA JOLLA, Calif.--(BUSINESS WIRE)--AeroRx Therapeutics, Inc., a clinical-stage biopharmaceutical company developing proprietary nebulized combination therapies for chronic respiratory diseases, today announced the closing of a $21 million Series A financing led by Avalon BioVentures, with participation from Correlation Ventures, Alexandria Venture Investments, and others. Proceeds will support late-stage clinical development of AeroRx’s lead candidate, inhaled AERO-007, the first nebulized LABA/LAMA combination in development as a potential first-line maintenance therapy for chronic obstructive pulmonary disease (COPD). “With this Series A financing, we are well positioned to advance AERO-007 into a Phase 2b dose-optimization study and prepare for late-stage, NDA-enabling development,” said Ahmet Tutuncu, M.D., Ph.D., Co-founder and CEO of AeroRx Therapeutics. Data from a completed Phase 2a clinical study of AERO-007 demonstrated that AERO-007 was well tolerated in patients with moderate to severe COPD, and provided rapid-onset, and clinically meaningful, sustained bronchodilation through 24 hours at both low and high doses. “With this Series A financing, we are well positioned to advance AERO-007 into a Phase 2b dose-optimization study and prepare for late-stage, NDA-enabling development,” said Ahmet Tutuncu, M.D., Ph.D., Co-founder and Chief Executive Officer of AeroRx Therapeutics. “Our Phase 2a study data further support AERO-007’s potential as a once-daily nebulized LABA/LAMA combination, designed to address a major unmet need for underserved COPD patients.” “Dual bronchodilation via handheld inhalers is the standard of care, but millions of patients remain poorly controlled due to difficulties with inhaler technique,” said Jay Lichter, Ph.D., Managing Partner at Avalon BioVentures. “AeroRx has the opportunity to deliver meaningful clinical benefit by bringing the preferred guideline therapy to patients in a nebulized form that is designed for full dosing and improved adherence.” The Phase 2a clinical trial was a randomized, double-blind, placebo-controlled, single-dose, three-period crossover that enrolled 16 adults with moderate-to-severe COPD. Both the low- and high-dose treatments of AERO-007 delivered clinically meaningful, statistically significant improvements in forced expiratory volume in one second (FEV1, the standard efficacy parameter based on serial spirometry assessment) compared to placebo. Inhaled AERO-007 was well tolerated with a tolerability and systemic drug exposure profile comparable to the previously approved drugs with the individual active components. About AERO-007 AERO-007 combines the long-acting, FDA-approved bronchodilators indacaterol (LABA) and glycopyrrolate (LAMA) in a proprietary formulation for delivery via a 510(k)-cleared standard jet nebulizer. More than 16 million people in the United States are diagnosed with COPD, posing a significant economic and social burden, and as many as 50 percent remain symptomatic even while using FDA-approved LABA/LAMA maintenance therapy delivered via inhalers (1). Studies also show that up to 75 percent of patients do not receive the full therapeutic dose from handheld inhaler devices, which demand coordination and forceful inhalation (2). Nebulized delivery offers a passive-breathing alternative that can provide more consistent dosing for patients who find inhalers challenging, particularly older adults and those with advanced COPD, who are at high risk for exacerbations, hospitalization, and disease progression (3). References: (1) American Lung Association, accessed July 24, 2025; Boers et al. JAMA Network Open 2023; Molimard et al. Eur Respir J 2017 (2) Kocks et al. BMC Pulm Med 2023 (3) Crater et al. Ther Adv Respir Dis 2022; Barjaktarevic et al. Int J COPD 2020 About AeroRx Therapeutics AeroRx Therapeutics is a clinical-stage biopharmaceutical company developing proprietary, combination products for nebulized delivery to improve the treatment of chronic respiratory diseases. The company’s lead product candidate, inhaled AERO-007, is the first potential nebulized LABA/LAMA fixed-dose combination drug in clinical development as a potential first-line maintenance therapy for COPD and has the potential to help millions of patients who remain symptomatic, or poorly served, under existing drugs delivered via handheld inhalers or nebulized LABA or LAMA monotherapy. A second program, AERO-111, is in development as the first potential nebulized LABA/LAMA/ICS triple therapy, for patients who escalate beyond dual bronchodilators. AeroRx’s leadership team has decades of expertise in aerosol drug delivery, clinical development, and regulatory strategy and guided multiple respiratory therapies from concept to regulatory approval. AeroRx is headquartered in the Avalon BioVentures Accelerator in La Jolla, California. For more visit, www.aerorxtx.com.

临床2期临床结果

2025-10-07

·EndPoints

AeroRx closes $21M Series A in bid to capitalize on COPD momentum

A respiratory biotech that launched Tuesday morning aims to take advantage of excitement in COPD drug development spurred by two recent deals. AeroRx Therapeutics took the wraps off a $21 million Series A that it’s using to get its lead program through Phase 2b testing in chronic obstructive pulmonary disease, or COPD. It’s the same category that spurred Merck’s $10 billion acquisition of Verona Pharma and GSK’s partnership with Hengrui Pharma that could be worth $12 billion if everything pans out. The AeroRx drug, known as AERO-007, is a nebulized reformulation of two approved compounds — indacaterol and glycopyrrolate — that use different mechanisms of action. Indacaterol is a long-acting beta agonist (LABA), while glycopyrrolate is a long-acting muscarinic agonist (LAMA). Combining LABAs and LAMAs is common when treating COPD. AeroRx CEO Ahmet Tutuncu said the FDA has approved five such products. An inhaler combination of indacaterol and glycopyrrolate was approved in 2015 as Utibron, which was developed by Novartis and out-licensed to Sunovion Pharmaceuticals a year later. (Sunovion is now owned by Sumitomo Pharma.) All the approvals are for inhalers with dry powder, which is more difficult for older and sicker patients to use, Tutuncu said. AeroRx believes it can be the first company to offer a nebulized formulation as a first-line maintenance therapy in COPD. “It’s a different delivery technology, or full dose delivery, for those patients who need to be on nebulized medicines,” Tutuncu said. “A significant number of COPD patients who are typically getting older, they are on inhalers, but they are the ones who end up in hospitals with exacerbations for symptom control, and therefore they need to be on nebulized medicine.” So far, AeroRx has run a small Phase 2a study with 16 patients that suggested AERO-007 could be dosed once daily. In the Phase 2b trial, researchers plan to test once-daily and twice-daily doses. Most other details about the trial remain undisclosed until after discussions with the FDA, according to Tutuncu, including how long it’s expected to last. But because both components of AERO-007 are already approved, Tutuncu expects an “abbreviated” late-stage development process comprising the Phase 2b and Phase 3 trials. The trials will also enroll all COPD patients, and if AERO-007 wins approval, AeroRx plans to market it for patients older than 65 years old. The company also has another preclinical program called AERO-111, which is a triple combination nebulized COPD treatment. (There are two approved triple-combo inhalers.) In addition to a LABA and LAMA compound, AERO-111 also includes a corticosteroid. Tutuncu said the company is still figuring out which one to use. AeroRx’s Series A comes about 18 months after it closed a $6 million seed round in the spring of last year. With the new cash in hand, AeroRx is aiming to capitalize on the recent momentum in COPD following the Merck and GSK deals. “Those were two really important validation points for the interest from big pharma for nebulized delivery in the respiratory space, and particularly in the COPD space,” Tutuncu said. “We’re very excited about that potential for collaboration with pharma down the road.”

临床2期上市批准并购

100 项与醋酸茚达特罗相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D11009	醋酸茚达特罗	R03AC18	-

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适应症	最高研发状态	国家/地区	公司	日期
哮喘	临床2期	斯洛伐克	Novartis Pharma AG	2012-08-01
持续性哮喘	临床2期	法国	Novartis Pharmaceuticals Corp.	2009-06-01
持续性哮喘	临床2期	德国	Novartis Pharmaceuticals Corp.	2009-06-01
持续性哮喘	临床2期	意大利	Novartis Pharmaceuticals Corp.	2009-06-01
呼吸困难	临床2期	德国	Novartis AG	2008-02-01
慢性阻塞性肺疾病	临床2期	德国	Novartis AG	2008-02-01

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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


NCT02892019 (Pubmed \| Clin Drug Investig)	临床2期	儿童哮喘	80	Indacaterol 75 µg	鏇網壓積構廠鑰襯糧築(廠餘餘觸齋鏇夢顧壓夢) = improved 鏇壓築遞觸製鹽鏇築鑰 (襯鑰願憲淵願憲鹽繭網 ) 更多	积极	2023-09-01
				Indacaterol 150 µg
NCT02892019 (CTgov)	临床2期	哮喘	79	Indacaterol acetate 150 μg (Indacaterol Acetate 150 μg o.d.)	鑰鬱築遞齋網糧積憲積(壓鬱構顧淵遞獵窪選選) = 廠構鹽艱積簾觸餘膚鹹壓範鑰遞壓壓壓憲範壓 (積鬱鑰鑰鏇鑰願憲構鏇, 0.1664) 更多	-	2020-01-27
				Indacaterol acetate 75 μg (Indacaterol Acetate 75 μg o.d.)	鑰鬱築遞齋網糧積憲積(壓鬱構顧淵遞獵窪選選) = 膚鏇觸衊鑰膚網廠鏇廠壓範鑰遞壓壓壓憲範壓 (積鬱鑰鑰鏇鑰願憲構鏇, 0.2521) 更多
NCT01609478 (CTgov)	临床2期	哮喘 \| 持续性哮喘	335	indacaterol+mometasone furoate (Indacaterol Acetate 75 µg)	製鹽製蓋製鹽襯簾鹹鑰(糧壓艱鹹艱膚觸積範窪) = 襯鹹鏇蓋膚構壓蓋願鑰壓齋夢鹹製築憲壓鹹憲 (構蓋構鏇製齋壓鏇襯鹹, 0.0283) 更多	-	2014-09-09
				indacaterol+mometasone furoate (Indacaterol Acetate 150 µg)	製鹽製蓋製鹽襯簾鹹鑰(糧壓艱鹹艱膚觸積範窪) = 構艱壓鬱製鏇製獵夢構壓齋夢鹹製築憲壓鹹憲 (構蓋構鏇製齋壓鏇襯鹹, 0.0281) 更多
ERS2014	N/A	哮喘	335	Indacaterol acetate 150 µg	積鏇繭窪遞鏇簾繭淵範(夢醖齋鹹鏇遞憲築窪淵) = 觸淵糧膚觸醖簾醖膚構糧繭獵獵選鏇繭淵鏇遞 (繭餘鹽選壓積鏇顧鹹製 )	积极	2014-09-01
				Indacaterol acetate 75 µg	積鏇繭窪遞鏇簾繭淵範(夢醖齋鹹鏇遞憲築窪淵) = 願鑰獵簾繭艱範繭鹹窪糧繭獵獵選鏇繭淵鏇遞 (繭餘鹽選壓積鏇顧鹹製 )
NCT00927901 (CTgov)	临床2期	持续性哮喘	30	Indacaterol Maleate (Indacaterol Maleate 400 μg)	艱艱淵鑰窪獵觸顧築鹽(鏇簾願繭襯壓獵網鬱廠) = 獵蓋鬱齋鹽壓築夢衊顧壓淵齋構憲艱壓範壓齋 (觸築醖顧鏇廠構築窪膚, 餘蓋淵選鬱憲遞鏇襯範 ~ 築積廠鹹餘築網獵繭衊) 更多	-	2011-08-30
				Indacaterol Acetate (Indacaterol Acetate 400 μg)	艱艱淵鑰窪獵觸顧築鹽(鏇簾願繭襯壓獵網鬱廠) = 糧糧鹽簾艱簾鹹夢醖願壓淵齋構憲艱壓範壓齋 (觸築醖顧鏇廠構築窪膚, 鬱衊憲齋壓願築築獵鏇 ~ 鏇顧鬱醖繭醖憲繭膚鬱) 更多
NCT00636961 (CTgov)	临床2期	呼吸困难 \| 慢性阻塞性肺疾病	27	Indacaterol (Indacaterol 300ug)	繭壓鬱獵願衊衊鏇艱夢(簾淵願衊觸觸觸網廠廠) = 憲選餘構網觸窪遞製獵衊選餘窪築衊窪廠築鑰 (憲鹽窪遞鑰遞醖壓窪餘, 網範窪壓選糧選蓋選鬱 ~ 願構構醖壓構顧遞艱鏇) 更多	-	2011-08-30
				placebo (Placebo)	繭壓鬱獵願衊衊鏇艱夢(簾淵願衊觸觸觸網廠廠) = 糧鑰蓋鏇鬱鬱齋鹽壓網衊選餘窪築衊窪廠築鑰 (憲鹽窪遞鑰遞醖壓窪餘, 鏇顧鹹鹽繭齋壓鏇壓範 ~ 簾獵繭鑰憲鹽構憲淵餘) 更多