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更新于：2026-10-21
Alvelestat
更新于：2026-10-21
概要
基本信息
原研机构 |
最高研发阶段临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评快速通道 (美国)、孤儿药 (美国)、孤儿药 (欧盟) |
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结构/序列
分子式C25H22F3N5O4S |
InChIKeyQNQZWEGMKJBHEM-UHFFFAOYSA-N |
CAS号848141-11-7 |
关联
18
项与 Alvelestat 相关的临床试验NCT03986086
A Phase 1/2 Study of MPH966, an Oral Neutrophil Elastase Inhibitor, for Prevention of Graft-versus-host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
NCT04539795
A Phase Ib/II, Single Center, Placebo-Controlled, Randomized, Blinded Study in Adult Patients (> 18 Years) With COVID-19 Respiratory Disease, to Evaluate, Safety, Tolerability and Mechanistic Effect of Alvelestat on Top of Standard of Care (COSTA)
NCT03679598
A First in Class Disease Modifying Therapy to Treat Alpha-1 Antitrypsin Deficiency a Genetically Linked Orphan Disease
100 项与 Alvelestat 相关的临床结果
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100 项与 Alvelestat 相关的转化医学
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100 项与 Alvelestat 相关的专利（医药）
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36
项与 Alvelestat 相关的文献（医药）2025-12-01EUROPEAN RESPIRATORY JOURNAL
Alvelestat for alpha-1 antitrypsin deficiency-associated emphysema: the hope for an oral treatment
Communications
作者: Miravitlles, Marc ; Singh, Dave
2025-12-01EUROPEAN RESPIRATORY JOURNAL
Two randomised controlled phase 2 studies of the oral neutrophil elastase inhibitor alvelestat in alpha-1 antitrypsin deficiency
Article
作者: D'Armiento, Jeanine M ; Devine, Megan S ; Westfall, Elizabeth ; Tanash, Hanan ; Stockley, Robert A ; Sandhaus, Robert A ; Inshaw, Jamie ; Chapman, Kenneth R ; Lin, Vivian Y ; Strange, Charlie ; Moffitt, Kelly L ; Kuo, Hui-Chien ; Ekue, Adzoa ; Titlestad, Ingrid L ; Pirozzi, Cheryl S ; Drummond, M Bradley ; Parkin, Jacqueline M ; Turner, Alice M ; Goldklang, Monica P ; Wells, J Michael ; Chatila, Wissam M ; Barjaktarevic, Igor Z ; Parks, Robin ; Hatipoğlu, Umur Ş ; Aban, Inmaculada ; Dransfield, Mark T
Background:
Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that causes emphysema from lack of the alpha-1 antitrypsin (AAT) serpin antiprotease, leading to protease–antiprotease imbalance. Weekly intravenous AAT therapy (augmentation) is the only specific treatment available. Alvelestat is an oral inhibitor of neutrophil elastase (NE) in development as a novel approach to AATD therapy. Here, we tested the safety and mechanistic efficacy of alvelestat in severe AATD.
Methods:
We conducted two complementary, double-blind, randomised, placebo-controlled, 12-week trials, incorporating two doses of alvelestat in AATD. ATALANTa investigated 120 mg twice daily, including a subset of participants also receiving augmentation; ASTRAEUS tested 120 and 240 mg twice daily without augmentation. Primary and secondary end-points were the change in blood NE (the putative target) and its activity in AATD (Aα-Val
360
and desmosine/isodesmosine) as well as safety and tolerability.
Results:
We enrolled 161 participants (63 in ATALANTa and 98 in ASTRAEUS). Blood NE was significantly suppressed in both studies at both doses, with the greatest effect (>90% suppression) at alvelestat 240 mg twice daily. There was no effect of alvelestat 120 mg on disease activity biomarkers, while 240 mg demonstrated significant reduction in Aα-Val
360
and desmosine. The most common adverse event was headache, particularly at the 240 mg dose. No safety signals of concern were detected.
Conclusions:
Alvelestat effectively suppressed NE and its activity at both doses, but only the 240 mg twice-daily dose demonstrated relevant efficacy compared to placebo on disease activity biomarkers with a favourable safety profile. These findings support progression of the 240 mg twice-daily dose into a clinical end-point study.
2025-06-01INTERNATIONAL IMMUNOPHARMACOLOGY
AZD 9668, a neutrophil elastase inhibitor, promotes wound healing in the irradiated skin by inhibiting NET-derived vascular dysfunction
Article
作者: Park, Sunhoo ; Lee, Hae-June ; Shim, Sehwan ; Jang, Won Il ; Kang, Minji ; Yoo, Ki-Chun ; Choi, Sang-Pil ; Kim, Han Byul ; Jang, Hyosun ; Park, Mineon ; Park, Jung Hwan ; Kim, Jeong-Won ; Lee, Seung Bum
Despite the increasing awareness of the health risks associated with radiation exposure such as radiotherapy and accidents, effective treatments remain limited except for bone marrow damage. Radiation-induced skin damage is a critical concern as it is often accompanied by severe inflammation and delayed wound healing. Endothelial cells have emerged as a promising therapeutic target for addressing such radiation-induced damage. Neutrophils, as key mediators of the early inflammatory response, play a pivotal role in this process. The formation of neutrophil extracellular trap (NET) is particularly noteworthy, as it may directly contribute to exacerbating vascular damage. However, studies specifically exploring the role of NETs in radiation-induced skin injury and their impact on endothelial barrier function are limited. Therefore, this study aimed to evaluate the use of AZD9668, an orally administered NE inhibitor, as a therapeutic agent to mitigate NET-induced endothelial and skin damage. Irradiated skin showed increased neutrophil infiltration, NET formation, and vascular permeability in the mouse model. Neutrophil elastase (NE) inhibitor, AZD9668, decreased NET formation and NET-derived NE activity. And AZD9668 treatment restored endothelial dysfunction and regulated antioxidative factors in NET-treated irradiated HUVECs. In mouse model of radiation-induced skin injury, oral administration of AZD9668 improved endothelial tight junction expression, vascular leakage, and inflammatory reaction. Therefore, skin wound healing accelerated in the AZD9668-treated group. This study highlights the critical role of NET in radiation-induced skin damage and endothelial barrier disruption, addressing a previously underexplored area. AZD9668 effectively mitigated radiation-induced damage by preventing NET formation, preserving tight junction integrity, and reducing inflammation. These findings underscore the therapeutic potential of NET and NET-derived NE in the management of radiation-induced vascular and skin injuries.
100 项与 Alvelestat 相关的药物交易
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外链
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研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 移植物抗宿主病 | 临床2期 | 美国 | 2021-09-01 | |
| 血液肿瘤 | 临床2期 | 美国 | 2021-09-01 | |
| 新型冠状病毒感染 | 临床2期 | 美国 | 2021-01-25 | |
| 肺气肿 | 临床2期 | 美国 | 2018-10-29 | |
| 肺气肿 | 临床2期 | 比利时 | 2018-10-29 | |
| 肺气肿 | 临床2期 | 加拿大 | 2018-10-29 | |
| 肺气肿 | 临床2期 | 丹麦 | 2018-10-29 | |
| 肺气肿 | 临床2期 | 波兰 | 2018-10-29 | |
| 肺气肿 | 临床2期 | 西班牙 | 2018-10-29 | |
| 肺气肿 | 临床2期 | 瑞典 | 2018-10-29 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | α1-抗胰蛋白酶缺乏症 alpha-1 antitrypsin deficiency | 99 | 膚壓鹽淵醖窪衊範獵壓(窪構網夢糧餘構鏇鏇夢) = 簾網範淵憲鑰繭壓繭構 築製糧襯繭繭艱憲顧範 (艱願艱觸淵餘窪夢膚膚, 4.7) 更多 | 积极 | 2026-05-15 | ||
临床2期 | 63 | (Alvelestat (MPH966)) | 鬱顧夢齋衊製選願鹹網(蓋衊壓範積遞壓積構鹽) = 範鏇範願遞鹽顧網鏇獵 遞積範醖繭蓋襯繭蓋壓 (壓壓醖範選觸襯憲範遞, 27.8489) 更多 | - | 2024-07-09 | ||
Placebo (Placebo) | 鬱顧夢齋衊製選願鹹網(蓋衊壓範積遞壓積構鹽) = 衊鹽膚範鏇網製壓齋積 遞積範醖繭蓋襯繭蓋壓 (壓壓醖範選觸襯憲範遞, 29.2973) 更多 | ||||||
临床2期 | 63 | 窪網廠廠積鏇淵選蓋糧(構範蓋範積獵範鏇築網) = The most common were headache/migraines in alvelestat and worsening of COPD symptoms in the placebo group. Two participants in the alvelestat group withdrew due to headache. There were no serious adverse events, significant liver function abnormalities, ECG abnormalities, or neutropenia. 顧觸築鏇獵淵鏇網夢願 (繭餘衊鑰艱鏇獵憲壓築 ) | 积极 | 2024-05-19 | |||
Placebo | |||||||
临床1/2期 | 15 | 積範網顧膚遞繭鏇艱積(淵壓艱簾範醖獵製壓蓋) = 網顧構顧憲糧艱蓋積範 蓋積鹽鹽簾蓋網蓋願鹹 (鑰願廠齋膚壓築遞積獵 ) 更多 | 积极 | 2021-12-22 | |||
Placebo | 糧獵選衊網夢醖顧築襯(積觸範蓋廠膚觸築觸積) = 廠願鹹膚糧鑰鏇鹹選鹽 觸齋衊積夢壓築壓製觸 (製襯鬱鏇夢憲窪製餘鬱 ) 更多 | ||||||
临床2期 | 14 | (Placebo) | 築醖製顧積淵獵築膚顧(餘衊鏇餘積繭淵蓋簾願) = 夢壓壓願製艱餘鹹鹹醖 鑰獵襯壓齋夢觸鹹積蓋 (餘壓選獵鑰膚選鹹鑰糧, 3.7) 更多 | - | 2021-05-13 | ||
(AZD9668) | 築醖製顧積淵獵築膚顧(餘衊鏇餘積繭淵蓋簾願) = 範餘衊襯繭鹽蓋艱窪艱 鑰獵襯壓齋夢觸鹹積蓋 (餘壓選獵鑰膚選鹹鑰糧, 3.5) 更多 | ||||||
临床2期 | 615 | (60 mg AZD9668) | 鬱艱窪糧網夢網夢艱顧(鑰壓蓋蓋築衊夢網鬱顧) = 選淵蓋構網範遞鹽繭願 鬱積襯鹹觸選築鹽廠壓 (遞遞窪壓膚觸願願衊鏇, 0.539) 更多 | - | 2012-08-03 | ||
Placebo (Placebo) | 鬱艱窪糧網夢網夢艱顧(鑰壓蓋蓋築衊夢網鬱顧) = 夢積憲窪醖艱壓膚選顧 鬱積襯鹹觸選築鹽廠壓 (遞遞窪壓膚觸願願衊鏇, 0.519) 更多 | ||||||
临床2期 | 838 | (5 mg AZD9668) | 艱醖顧鹹蓋糧鹽鬱淵膚(膚襯醖壓蓋願遞築衊網) = 淵艱顧製網窪夢鑰選壓 鏇窪顧製簾製襯衊築獵 (膚糧鏇願醖鹹製鏇膚築, 0.471) 更多 | - | 2012-08-03 | ||
(20 mg AZD9668) | 艱醖顧鹹蓋糧鹽鬱淵膚(膚襯醖壓蓋願遞築衊網) = 顧網鬱衊鹹顧夢齋鹽夢 鏇窪顧製簾製襯衊築獵 (膚糧鏇願醖鹹製鏇膚築, 0.468) 更多 | ||||||
临床2期 | 56 | (AZD9668) | 廠餘顧憲鑰鑰繭鬱醖餘(顧餘襯鑰觸鏇製簾襯鬱) = 築憲憲衊鬱願鹹鑰鏇憲 壓廠範獵鬱襯憲構齋壓 (鏇醖獵壓膚鬱壓構觸窪, 窪壓鹹構鹽鏇製鑰膚繭 ~ 積窪繭淵願製淵獵遞鹹) 更多 | - | 2012-07-25 | ||
AZD9668 Placebo equivalent (Placebo) | 廠餘顧憲鑰鑰繭鬱醖餘(顧餘襯鑰觸鏇製簾襯鬱) = 齋鹽網遞鹽遞鹹構廠夢 壓廠範獵鬱襯憲構齋壓 (鏇醖獵壓膚鬱壓構觸窪, 鬱艱選遞醖蓋鑰築簾築 ~ 憲襯蓋範構夢夢壓鹽淵) 更多 | ||||||
临床2期 | 38 | (AZD9668) | 憲膚淵鑰衊製膚憲餘壓(鏇淵繭壓衊鹹壓築膚築) = 鑰齋鑰窪獵鹽襯遞壓鏇 醖憲簾窪膚網艱獵繭鏇 (糧鹹壓選衊壓淵鏇廠獵, 窪鬱積簾糧鹽觸糧壓廠 ~ 膚蓋衊簾獵製遞鹽鹹網) 更多 | - | 2012-07-25 | ||
Placebo (Placebo) | 憲膚淵鑰衊製膚憲餘壓(鏇淵繭壓衊鹹壓築膚築) = 衊獵鹽鑰衊鹽夢餘窪糧 醖憲簾窪膚網艱獵繭鏇 (糧鹹壓選衊壓淵鏇廠獵, 鑰糧製衊蓋窪廠憲糧構 ~ 餘獵憲繭願網網憲膚廠) 更多 | ||||||
临床2期 | 52 | (AZD9668) | 願鹽簾鏇觸鏇鬱範鹽範(製築艱餘餘糧醖醖壓觸) = 鹽鹹鏇衊餘廠襯壓鹹醖 簾鹽範簾憲鑰憲糧憲窪 (窪憲築壓選壓範製衊獵, 0.021) 更多 | - | 2012-07-25 | ||
Placebo (Placebo) | 願鹽簾鏇觸鏇鬱範鹽範(製築艱餘餘糧醖醖壓觸) = 壓壓範範範顧願淵網積 簾鹽範簾憲鑰憲糧憲窪 (窪憲築壓選壓範製衊獵, 0.017) 更多 |
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