恩塞芬汀(Ensifentrine) - 药物靶点：PDE3 x PDE4_在研适应症：慢性阻塞性肺疾病，非囊性支气管扩张，哮喘_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Ensifentrine (USAN/INN)、恩司芬群、RPL 554

+ [4]

靶点

PDE3 x PDE4

作用方式

抑制剂

作用机制

PDE3抑制剂(磷酸二酯酶3抑制剂)、PDE4抑制剂(磷酸二酯酶4抑制剂)

治疗领域

呼吸系统疾病免疫系统疾病遗传病与畸形+ [2]

在研适应症

慢性阻塞性肺疾病非囊性支气管扩张哮喘+ [1]

非在研适应症

慢性哮喘新型冠状病毒感染炎症+ [2]

原研机构

Verona Pharma Plc

在研机构

优锐医药科技（上海）有限公司

Ligand UK Ltd.Verona Pharma, Inc.

+ [1]

非在研机构-

权益机构

Rhinopharma Ltd.

Verona Pharma Plc

Ligand Pharmaceuticals, Inc.

+ [2]

最高研发阶段批准上市

首次获批日期

美国 (2024-06-26),

慢性阻塞性肺疾病

最高研发阶段(中国)临床3期

特殊审评-

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结构/序列

分子式C26H31N5O4

InChIKeyCSOBIBXVIYAXFM-UHFFFAOYSA-N

CAS号298680-25-8

关联

20

项与恩塞芬汀相关的临床试验

NCT07016412

/ Not yet recruiting临床2期

A Phase IIb, Randomized, Double-blind, Placebo- Controlled, Parallel Group Study to Assess the Efficacy and Safety of Ensifentrine-glycopyrrolate Fixed-dose Combination at Two Dose Levels Compared to Glycopyrrolate or Ensifentrine Monotherapy in Subjects With COPD

This study will assess the safety and efficacy of fixed dose combinations of ensifentrine with two different glycopyrrolate dose levels compared to placebo and to the individual components of the fixed dose combinations, each administered twice a day via standard jet nebulizer, in adult subjects with chronic obstructive pulmonary disease (COPD).

开始日期2025-07-31

申办/合作机构

Verona Pharma Plc

NCT06559150

/ Recruiting临床2期

A Phase II, Randomized, Double-Blind, Placebo- Controlled Study of Ensifentrine in Subjects With Non-Cystic Fibrosis Bronchiectasis

This study is a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of ensifentrine inhalation suspension (3 mg) delivered twice daily via standard jet nebulizer over at least 24 weeks, compared to placebo, in subjects with non-cystic fibrosis bronchiectasis (NCFBE).

开始日期2024-09-11

申办/合作机构

Verona Pharma Plc

NCT06460493

/ Completed临床3期

A Study Assessing the Effect of Ensifentrine on CAT™ Scores Over 12 Weeks in Subjects With Moderate to Severe COPD

The purpose of this open-label, single center trial is to assess the effect of twice daily nebulized ensifentrine (3 mg) on COPD symptoms measured by the COPD Assessment Test (CAT™) scores over 12 weeks in subjects with symptomatic, moderate to severe COPD, taking maintenance LAMA/LABA or LAMA/LABA/ICS therapy. Subjects will continue the maintenance treatment during study participation.

开始日期2024-06-11

申办/合作机构

Verona Pharma Plc

[+1]

100 项与恩塞芬汀相关的临床结果

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100 项与恩塞芬汀相关的转化医学

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100 项与恩塞芬汀相关的专利（医药）

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67

项与恩塞芬汀相关的文献（医药）

2025-12-01·Chronic Respiratory Disease

Ensifentrine in COPD patients taking long-acting bronchodilators: A pooled post-hoc analysis of the ENHANCE-1/2 studies

Article

作者: Rickard, Kathleen Ann ; Dransfield, Mark ; Anzueto, Antonio ; Marchetti, Nathaniel ; Dixon, Amy L ; Reyner, Daniel ; Rheault, Tara ; Kalhan, Ravi

Background:

The efficacy and safety of ensifentrine, a novel PDE3/PDE4 inhibitor, were previously evaluated in the ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) trials. Here, we present a pooled post-hoc subgroup analysis of patients according to background chronic obstructive pulmonary disease (COPD) maintenance medication regimens.

Objective:

This analysis aimed to explore the efficacy and safety of ensifentrine in patients receiving long-acting muscarinic antagonists (LAMA) or long-acting beta-agonists with inhaled corticosteroids (LABA + ICS).

Methods:

Eligible patients had moderate to severe COPD, were aged 40–80 years, and were symptomatic at randomization. Patients were randomized 5:3, receiving twice-daily ensifentrine 3 mg or placebo via standard jet nebulizer over 24 weeks.

Results:

The pooled post-hoc analysis included 485 LAMA patients and 272 LABA + ICS patients. Ensifentrine showed lung function improvement over placebo at week 12, including average FEV1 AUC0–12 h in the LAMA (placebo-corrected least squares mean change from baseline [LSMC], 92 mL; 95% CI, 54, 131; p < 0.001) and LABA + ICS subgroups (LSMC, 74 mL; 95% CI, 27, 121; p = 0.002). Ensifentrine reduced the rate and risk of exacerbations in both LAMA (48% and 50%, respectively) and LABA + ICS (51% and 56%, respectively) subgroups. Ensifentrine-treated patients reported improvement in symptoms and quality of life over 24 weeks. The safety profile of ensifentrine in each subgroup was similar to the profile in the pooled modified intention-to-treat population.

Conclusions:

Nebulized ensifentrine offers a novel non-steroidal anti-inflammatory and bronchodilator treatment added to existing LAMA or LABA + ICS treatment options in patients with moderate to severe, symptomatic COPD.

2025-06-03·Expert Review of Respiratory Medicine

Ensifentrine vs placebo for chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized clinical trials

Review

作者: Peralta-Jiménez, Gonzalo Alberto ; Roca Mora, Maria Meritxell ; Carvalhal, Giulia ; Barrera, Vivian ; Ayasa, Laith ; Aljazeeri, Jafar ; Advani, Kavita ; Anzueto, Antonio

INTRODUCTION:

To evaluate the efficacy and safety of ensifentrine in chronic obstructive pulmonary disease (COPD).

METHODS:

We searched electronic databases and registries until 25 January 2025, for randomized clinical trials (RCTs) comparing ensifentrine vs placebo in patients with COPD. Primary outcomes include forced expiratory volume in one second (FEV₁) area under the curve (AUC), peak FEV₁, and morning trough FEV₁.

RESULTS:

Ten RCTs involving 2,589 patients were included. Compared with placebo, ensifentrine improved FEV₁ AUC by 104.24 ml (95% CI, 74.03 to 133.44; moderate certainty) on day 1 and by 90.37 ml (95% CI, 54.94 to 125.81; moderate certainty) at study end. Ensifentrine increased peak FEV₁ by 140.99 ml on day 1 (95% CI, 107.48 to 174.5; moderate certainty) and by 118.98 ml at the final assessment (95% CI, 86.49 to 151.47; moderate certainty). Ensifentrine improved morning trough FEV₁ by 42.15 ml (95% CI, 19.87 to 64.43; high certainty). Dose-response analysis showed a bell-shaped curve for all outcomes. Ensifentrine did not significantly differ from placebo in adverse events or improvements in COPD symptoms and quality of life.

CONCLUSIONS:

Compared with placebo, ensifentrine improved lung function in COPD. Larger RCTs are needed to integrate this bronchodilator benefit with patient-centered outcomes.

PROSPERO REGISTRATION:

CRD42024571928.

2025-05-03·EXPERT OPINION ON PHARMACOTHERAPY

Ensifentrine: a novel approach to redefining COPD management and implications for additional respiratory diseases

Review

作者: Jia, Shijing ; Subramanian, Shyam ; Sciurba, Frank C.

INTRODUCTION:

Ensifentrine, recently approved by the FDA for chronic obstructive pulmonary disease (COPD) maintenance treatment, is a novel inhaled therapy with a dual mechanism of action targeting phosphodiesterase (PDE)3 and PDE4. While long-acting bronchodilators and inhaled corticosteroids remain initial guideline-based COPD treatments, persistent symptoms and disease exacerbations highlight an existing unmet need. Ensifentrine offers both bronchodilator and anti-inflammatory benefits, offering the potential to address this treatment gap.

AREAS COVERED:

This article reviews the mechanism of action of ensifentrine, details supporting preclinical evidence, and summarizes key clinical studies. It further explores ensifentrine's potential impact on the COPD treatment landscape and its potential applicability in other pulmonary diseases.

EXPERT OPINION:

Ensifentrine's dual bronchodilator and anti-inflammatory action offer a promising adjunct to standard COPD treatments, particularly for patients with persistent symptoms despite conventional therapy. It improves lung function, meaningfully reduces exacerbation frequency, reduces symptoms, and enhances quality of life. Its inhaled delivery minimizes systemic exposure and side effects commonly observed with oral PDE inhibitors. Furthermore, its anti-inflammatory properties suggest potential applications in other chronic respiratory diseases, such as asthma and non-cystic fibrosis bronchiectasis.

260

项与恩塞芬汀相关的新闻（医药）

2025-06-10

·药智网

正大天晴COPD新药启动Ⅲ期临床

近日，正大天晴宣布，其吸入性PDE3/4双重抑制剂TQC3721混悬液获得国家药监局药品审评中心（CDE）批准开展Ⅲ期注册临床研究，用于慢性阻塞性肺疾病（COPD）的维持治疗。慢性阻塞性肺疾病（COPD，慢阻肺），是一种严重的慢性呼吸系统疾病，是全球第三大致死原因，每年导致超过300万人死亡，有“沉默的杀手”之称。在中国，COPD是国家高度关注的慢性呼吸道疾病之一，流调数据显示，中国约有1亿COPD患者。当前，COPD的治疗药物主要有吸入性糖皮质激素、支气管扩张剂、磷酸二酯酶-4抑制剂、抗生素、黏液溶解剂及抗氧化剂。但这些药物都存在一定的临床局限性：长效支气管扩张剂虽可一定程度减轻症状，但缺乏抗炎效应阻止疾病进展；吸入糖皮质激素（ICS）虽为抗炎药物，但在患者使用上有一定局限性，适用人群在GOLD指南中逐渐受到限制。2024年，Verona Pharma公司的恩司芬群（Ensifentrine，Ohtuvayre）获美国FDA批准上市，成为COPD治疗领域近20年以来首个获批上市的新机制吸入制剂。Ensifentrine是一款全球首创的磷酸二酯酶3/4（PDE3/4）抑制剂，其对PDE3和PDE4的双重抑制可产生叠加或协同效应，从而增强对支气管扩张、气道炎症和黏膜纤毛清除的作用。该药上市8个月累计销售额已达到1.14亿美元。目前该药在中国的三期临床试验ENHANCE-CHINA已取得积极顶线结果，预计很快将提交上市申请。而正大天晴的TQC3721是仅次于ensifentrine、全球进度第二的PDE3/4抑制剂。去年，TQC3721吸入混悬液两项研究成果登上欧洲呼吸学会国际大会（2024 ERS）。临床研究结果显示，TQC3721在单支扩剂和双支扩剂背景治疗的COPD患者中，肺功能和症状评分有显著改善，具有同类最优的潜力。相较于已上市PDE3/4产品，TQC3721的Ⅲ期临床研究将额外纳入双支扩剂背景治疗患者，覆盖更为广泛的COPD患者人群。此外，除吸入用混悬液外，TQC3721吸入粉雾剂正处在临床I期开发阶段，干粉剂型有望进一步提升患者的依从性。呼吸领域一直是正大天晴的重点研发领域，除了PDE3/4抑制剂，正大天晴还布局了P2X3、ROCK2及TSLP等多个创新靶点的产品管线，瞄准COPD、哮喘、慢性咳嗽和特发性肺纤维化（IPF）等存在重大未满足临床需求的疾病领域。此外，正大天晴不断拓展混悬液、干粉等多种吸入剂型技术平台的开发，以期进一步满足适合全年龄段、各类复杂病情的用药需求。此外，药智数据显示，国内在研PDE3/4抑制剂中，海思科的HSK39004和恒瑞医药的HRS-9821也已进入临床阶段。参考资料：https://mp.weixin.qq.com/s/0m7MTdQRdTHTmc1nASfZTQ声明：本内容仅用作医药行业信息传播，不代表药智网立场。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 小月石合作、投稿 | 马老师 18323856316（同微信）阅读原文，是受欢迎的文章哦

临床3期申请上市临床2期临床成功临床失败

2025-05-25

·新药前沿

第二款COPD生物药获批加入竞争

尽管未能摘得“首个COPD生物药”桂冠，葛兰素史克（GSK）对其IL-5抗体药物Nucala（美泊利珠单抗）在慢性阻塞性肺病（COPD）领域的潜力依然充满信心。经历本月初的意外延期后，这款药物新适应症终获FDA批准，成为美国FDA获批的第二个COPD生物制剂，也是近一年内第三个获批的COPD新疗法。5月22日，FDA批准Nucala作为附加维持疗法，用于治疗嗜酸性粒细胞表型且现有疗法控制不佳的成人COPD患者。此前，赛诺菲/再生元的Dupixent（度普利尤单抗）于2024年9月获批同类适应症，而Verona Pharma的Ohtuvayre（非生物制剂）则于2024年6月获批。尽管Dupixent与Ohtuvayre目标人群不同（前者针对频繁急性加重患者，后者针对持续性呼吸困难），但Nucala将与Dupixent在嗜酸性粒细胞水平升高的患者群体中展开直接竞争。GSK强调，Nucala的III期Matinee试验覆盖了更广泛的患者类型（包括单纯肺气肿、慢性支气管炎或两者兼具），而Dupixent试验未纳入单纯肺气肿患者，这将成为其差异化优势。GSK预计Nucala在COPD领域的年销售峰值将达5亿英镑（约6.69亿美元）。目前，Nucala在美国的单剂注射定价为3800美元（折扣前）。2024年，该药在原有四个适应症的全年销售额按固定汇率计算增长13%至33亿英镑（44亿美元），2025年第一季度销售额达4.44亿英镑（5.94亿美元），同比增长21%。随着Nucala的加入，COPD治疗领域竞争将更趋激烈。除GSK、赛诺菲外，阿斯利康也正在努力把其靶向于TSLP单抗Tezspire（tezepelumab）推进到COPD领域中。阿斯利康在今年3月底启动了2项Tezspire治疗COPD适应症的III期试验，计划2029年完成。此外，IL-33与其特异性受体ST2已有多款抗体药物进入到COPD的III期临床试验中了。延伸阅读：COPD晚期管线丰富，市场将大爆发本文由「新药前沿」微信公众号根据公开资料整理编辑，欢迎个人转发至朋友圈。媒体或机构转载授权请在「新药前沿」微信公众号留言公众号名称，审核通过后开通白名单获取转载授权，转载请标识来源。免责声明：本文仅作信息交流之目的，非投资建议或者治疗方案推荐，「新药前沿」微信公众号不对任何主体因使用本文内容而导致的任何损失承担责任。限于作者水平和专业知识所限，如有谬误，欢迎指正！

临床3期

2025-05-23

·ETPharma

GSK's asthma drug wins FDA approval to treat 'smoker's lung'

Bengaluru: The U.S. Food and Drug Administration has approved British drugmaker GSK 's asthma drug to treat some patients with a chronic lung disease commonly known as " smoker's lung ", the company said on Thursday. The approval expands the use of the drug, Nucala , as an add-on treatment for patients with a type of chronic obstructive pulmonary disease . Sanofi and Regeneron's blockbuster drug Dupixent and Verona Pharma's inhaled therapy Ohtuvayre are also approved for the condition, which affects the lungs, causing restricted airflow and breathing problems. GSK's Nucala is a monoclonal antibody that inhibits interleukin-5 , which helps regulate eosinophils, a type of white blood cell that causes inflammation in the lungs when overproduced. The regulator had set a target action date of May 7 for its decision on the drug. The approval, however, came two weeks later. This is the latest instance where the drug regulator has missed its deadline after mass layoffs as part of a major overhaul of federal health agencies under Secretary of Health and Human Services Robert F. Kennedy Jr. The approval was based on a late-stage trial, in which patients treated with Nucala and an inhaled maintenance therapy for up to 104 weeks had significantly reduced exacerbations by 21% compared to placebo. "There's a very high burden when you have severe exacerbations and end up being hospitalized. The aim is to keep patients out of the hospital, keep them stable, and keep them at home," GSK's Chief Commercial Officer Luke Miels said ahead of the approval. Nucala recorded 1.78 billion pounds ($2.38 billion) in total sales last year. The disease commonly affects cigarette smokers but can also be caused by air pollution and related occupational hazards. It is the fourth leading cause of death worldwide, according to the World Health Organization. (Reporting by Siddhi Mahatole and Sriparna Roy in Bengaluru; Editing by Sriraj Kalluvila and Vijay Kishore)

上市批准

100 项与恩塞芬汀相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11743	恩塞芬汀	-	DB16157

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
慢性阻塞性肺疾病	美国	Verona Pharma Plc	2024-06-26
慢性阻塞性肺疾病	美国	Verona Pharma, Inc.	2024-06-26

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
非囊性支气管扩张	临床2期	美国	Verona Pharma Plc	2024-09-11
非囊性支气管扩张	临床2期	意大利	Verona Pharma Plc	2024-09-11
非囊性支气管扩张	临床2期	西班牙	Verona Pharma Plc	2024-09-11
非囊性支气管扩张	临床2期	英国	Verona Pharma Plc	2024-09-11
新型冠状病毒感染	临床2期	美国	Verona Pharma, Inc.	2020-09-04
囊性纤维化	临床2期	英国	Verona Pharma Plc	2017-02-08
中度慢性阻塞性肺疾病	临床2期	-	Verona Pharma Plc	2017-01-01
慢性哮喘	临床2期	瑞典	Verona Pharma Plc	2015-04-01
慢性哮喘	临床2期	英国	Verona Pharma Plc	2015-04-01
哮喘	临床2期	荷兰	Verona Pharma Plc	-

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临床结果

适应症

分期

评价

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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


ENHANCE-1/2 (Pubmed \| Chron Respir Dis)	N/A	慢性阻塞性肺疾病维持	-	Ensifentrine 3 mg	選築襯鏇鬱遞鑰鹽鏇製(鹹餘鬱鬱蓋襯膚範鑰壓) = 鬱簾淵鏇鹽選獵膚網簾積築觸齋積繭繭築鏇繭 (遞衊願觸製鑰壓選廠製, 54 ~ 131)	积极	2025-12-01
				Ensifentrine (LAMA patients)	選築襯鏇鬱遞鑰鹽鏇製(鹹餘鬱鬱蓋襯膚範鑰壓) = 齋積觸製夢製蓋鏇蓋醖積築觸齋積繭繭築鏇繭 (遞衊願觸製鑰壓選廠製, 54 ~ 131) 更多
NCT05743075 (ENHANCE-CHINA, PRNewswire) 人工标引	临床3期	慢性阻塞性肺疾病	526	Ensifentrine	衊鹽鏇夢鹽築艱廠觸願(夢襯鬱餘糧蓋憲醖窪製) = 築淵壓憲壓襯蓋積築襯鏇簾憲餘網醖糧鹽選鑰 (簾鑰夢餘簾顧範齋願蓋 ) 达到更多	积极	2025-05-16
				Placebo	-
ENHANCE program (ATS2025)	临床3期	-	-	Ensifentrine 3 mg	構遞鬱鏇繭餘醖築衊鏇(齋糧積鏇淵膚夢鑰繭構) = 夢構鹹獵膚壓蓋鬱艱獵壓選顧齋廠繭繭鏇壓鑰 (膚艱鹽壓遞鏇觸簾夢顧, 0.2 ~ 2.6) 更多	积极	2025-05-16
				Placebo	構遞鬱鏇繭餘醖築衊鏇(齋糧積鏇淵膚夢鑰繭構) = 齋鹹觸願齋鏇廠鹽鹽淵壓選顧齋廠繭繭鏇壓鑰 (膚艱鹽壓遞鏇觸簾夢顧, -0.6 ~ 1.8) 更多
ENHANCE trials (ATS2025)	临床3期	慢性阻塞性肺疾病	-	Ensifentrine 3 mg	窪艱積積鏇衊製鏇艱選(願簾廠範艱製選鹽鬱鏇) = reduced (improved) with ensifentrine monotherapy vs placebo at Weeks 6, 12, and 24 鬱獵醖獵糧構構齋選淵 (壓顧壓衊窪築膚淵蓋淵 ) 更多	积极	2025-05-16
				Placebo
ATS2025	N/A	慢性阻塞性肺疾病维持	1,715	Ensifentrine 3 mg twice daily	範範繭築遞糧鏇獵鹽襯(簾窪醖衊糧衊廠鏇壓鹹) = 衊艱鑰蓋廠憲襯製築簾壓糧築憲夢餘襯獵觸衊 (構繭齋憲觸鬱願憲遞艱 ) 更多	积极	2025-05-16
ENHANCE program (ATS2025)	临床3期	慢性阻塞性肺疾病	-	Ensifentrine 3 mg	願網鬱鹹願築餘網淵糧(顧醖鹽鬱遞鏇築鏇鹽願) = 齋繭齋艱築網顧餘齋蓋製壓範範網淵廠蓋範構 (觸糧獵淵築願糧鬱糧餘 ) 更多	积极	2025-05-16
				Placebo	-
ENHANCE program (ATS2025)	临床3期	-	-	Ensifentrine 3 mg	顧繭觸範鏇膚簾醖選範(鑰願遞艱膚餘憲積窪獵) = 襯鬱廠糧鏇製構簾顧壓膚餘顧製簾鹹顧鹽簾憲 (壓糧網鬱壓鏇鹹齋遞淵 )	积极	2025-05-16
ATS2025	N/A	慢性阻塞性肺疾病	-	Ensifentrine	膚艱製糧鏇壓積觸簾醖(衊鹹願網遞醖觸鏇醖鏇) = 鹹餘選選壓糧憲選積顧糧衊獵鹹糧壓範鏇鏇築 (遞窪鬱憲糧獵網淵選餘, 19.87 ~ 64.43) 更多	积极	2025-05-16
ATS2025	N/A	慢性阻塞性肺疾病	-	Ensifentrine	構齋艱鏇遞願顧繭築醖(衊觸網壓鏇壓鑰壓選憲) = 廠鑰鏇襯憲顧餘餘夢範築觸餘鑰遞製蓋鹹鹹齋 (觸顧膚繭醖觸衊糧鏇鏇, 0.02 ~ 0.07) 更多	积极	2025-05-16
ATS2025	N/A	-	-	Ensifentrine (Male Rats)	醖鏇膚淵廠範選窪膚膚(鹽憲蓋選選壓夢積範蓋) = 鹽構餘構鬱憲範艱鑰鑰淵淵繭餘遞願構鏇觸鏇 (窪遞糧築顧觸顧蓋觸積 )	-	2025-05-16
				Ensifentrine (Female Rats)	醖鏇膚淵廠範選窪膚膚(鹽憲蓋選選壓夢積範蓋) = 襯積齋廠積糧鑰襯廠築淵淵繭餘遞願構鏇觸鏇 (窪遞糧築顧觸顧蓋觸積 )