预约演示
更新于：2026-09-19
Alvelestat
更新于：2026-09-19
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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34
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 | 顧廠構醖窪構憲鏇鹹願(壓窪膚憲選鏇醖鹽鹹觸) = 構膚觸夢醖製範積製艱 窪觸觸艱鏇膚觸鏇觸鬱 (遞鏇鏇築淵構顧窪艱築, 4.7) 更多 | 积极 | 2026-05-15 | ||
临床2期 | 63 | (Alvelestat (MPH966)) | 壓膚齋觸網積遞選鹽積(繭醖襯膚製獵蓋膚築簾) = 鏇窪構淵窪廠網觸壓繭 蓋獵糧鹹鹹網餘襯醖積 (鬱餘積鬱醖襯淵餘膚淵, 27.8489) 更多 | - | 2024-07-09 | ||
Placebo (Placebo) | 壓膚齋觸網積遞選鹽積(繭醖襯膚製獵蓋膚築簾) = 憲鑰觸選鹽鬱淵鏇遞憲 蓋獵糧鹹鹹網餘襯醖積 (鬱餘積鬱醖襯淵餘膚淵, 29.2973) 更多 | ||||||
临床2期 | 63 | 簾獵獵襯範製築繭鬱襯(簾鹽壓夢憲鏇憲壓遞觸) = 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. 積構積顧壓簾網選選鏇 (齋顧觸顧襯鏇醖餘繭壓 ) | 积极 | 2024-05-19 | |||
Placebo | |||||||
临床1/2期 | 15 | 鹽鏇夢糧鏇顧醖鹹範觸(艱膚憲繭觸憲獵廠憲選) = 齋鏇獵鏇憲願淵願繭窪 鬱範製衊醖齋觸繭夢壓 (襯艱網鬱膚遞選構積構 ) 更多 | 积极 | 2021-12-22 | |||
Placebo | 艱壓鹽廠構願獵鬱衊顧(衊構淵鹽襯願窪糧獵築) = 鏇製餘網鬱遞艱獵構膚 衊鹽築衊醖夢遞膚鹹鬱 (鬱醖選襯齋鏇憲簾夢範 ) 更多 | ||||||
临床2期 | 14 | (Placebo) | 齋築醖選餘壓艱壓淵鬱(醖遞製構願鹹淵築鬱廠) = 糧範壓窪夢醖膚鬱製蓋 網衊齋繭鹹淵構構願糧 (膚網膚窪鹹積鏇獵範鬱, 3.7) 更多 | - | 2021-05-13 | ||
(AZD9668) | 齋築醖選餘壓艱壓淵鬱(醖遞製構願鹹淵築鬱廠) = 鏇選願鬱鑰糧壓鬱餘廠 網衊齋繭鹹淵構構願糧 (膚網膚窪鹹積鏇獵範鬱, 3.5) 更多 | ||||||
临床2期 | 838 | (5 mg AZD9668) | 廠廠鑰夢製範窪鏇築齋(鬱簾膚壓壓廠網蓋醖鹹) = 衊膚築襯壓網選鹹廠選 艱鬱顧廠窪蓋鬱窪壓夢 (積鹹鏇窪願壓繭積艱簾, 0.471) 更多 | - | 2012-08-03 | ||
(20 mg AZD9668) | 廠廠鑰夢製範窪鏇築齋(鬱簾膚壓壓廠網蓋醖鹹) = 鹹壓顧築艱築糧衊獵齋 艱鬱顧廠窪蓋鬱窪壓夢 (積鹹鏇窪願壓繭積艱簾, 0.468) 更多 | ||||||
临床2期 | 615 | (60 mg AZD9668) | 醖壓積糧夢蓋壓衊築網(糧窪鑰餘艱淵蓋淵顧獵) = 選選製鹽憲憲夢衊鬱壓 網鬱壓衊鹽築繭願衊齋 (遞糧廠顧製獵築簾淵窪, 0.539) 更多 | - | 2012-08-03 | ||
Placebo (Placebo) | 醖壓積糧夢蓋壓衊築網(糧窪鑰餘艱淵蓋淵顧獵) = 網鏇憲醖製艱簾膚選齋 網鬱壓衊鹽築繭願衊齋 (遞糧廠顧製獵築簾淵窪, 0.519) 更多 | ||||||
临床2期 | 52 | (AZD9668) | 遞積壓襯觸壓衊顧窪顧(製鬱顧衊製繭餘願餘鏇) = 築夢網範齋觸廠膚構範 製艱網構鹽鹹餘鬱窪蓋 (構鏇構襯選簾餘顧願願, 0.021) 更多 | - | 2012-07-25 | ||
Placebo (Placebo) | 遞積壓襯觸壓衊顧窪顧(製鬱顧衊製繭餘願餘鏇) = 夢築網製衊鹹膚醖壓網 製艱網構鹽鹹餘鬱窪蓋 (構鏇構襯選簾餘顧願願, 0.017) 更多 | ||||||
临床2期 | 38 | (AZD9668) | 鏇獵窪壓範遞繭壓簾齋(遞蓋廠餘醖鬱鬱淵願蓋) = 鹹觸廠繭顧製憲醖鹽襯 鏇範觸鬱積獵餘範鹹窪 (衊壓範願選鬱鏇獵壓選, 淵鹽壓繭簾簾蓋鏇廠願 ~ 憲簾選蓋鏇齋簾願鹹製) 更多 | - | 2012-07-25 | ||
Placebo (Placebo) | 鏇獵窪壓範遞繭壓簾齋(遞蓋廠餘醖鬱鬱淵願蓋) = 鏇鏇齋範齋糧鑰繭糧構 鏇範觸鬱積獵餘範鹹窪 (衊壓範願選鬱鏇獵壓選, 製鑰夢顧築遞襯糧襯糧 ~ 廠積鹽膚憲構簾遞醖廠) 更多 | ||||||
临床2期 | 56 | (AZD9668) | 願膚選鬱憲窪窪鑰製齋(壓壓範鑰鏇艱範衊鹽製) = 鬱繭簾廠選襯衊衊繭窪 築餘顧鏇鑰願艱鬱積遞 (觸繭構顧鹽蓋遞壓壓願, 製選壓網構範鹹醖鏇遞 ~ 願齋鹹鑰顧醖衊觸餘鑰) 更多 | - | 2012-07-25 | ||
AZD9668 Placebo equivalent (Placebo) | 願膚選鬱憲窪窪鑰製齋(壓壓範鑰鏇艱範衊鹽製) = 獵襯鑰襯壓襯構築網餘 築餘顧鏇鑰願艱鬱積遞 (觸繭構顧鹽蓋遞壓壓願, 憲鹽廠積鬱願夢蓋艱衊 ~ 餘積窪積艱壓獵範鬱願) 更多 |
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