多奈单抗(Donanemab-AZBT) - 药物靶点：pGlu3Aβ_在研适应症：阿尔茨海默病引起的痴呆症，轻度认知障碍，阿尔茨海默症_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Donanemab、Donanemab (USAN)、N3pG-AB-monoclonal-antibody-Eli-Lilly

+ [12]

靶点

pGlu3Aβ

作用机制

焦谷氨酸 (3pE) 修饰型β-淀粉样蛋白抑制剂

治疗领域

神经系统疾病其他疾病

在研适应症

阿尔茨海默病引起的痴呆症轻度认知障碍阿尔茨海默症+ [4]

非在研适应症-

原研机构

Eli Lilly & Co.

在研机构

Eli Lilly & Co.Eli Lilly Nederland BVEli Lilly Canada, Inc.

+ [1]

非在研机构-

最高研发阶段批准上市

首次获批日期

美国 (2024-07-02),

阿尔茨海默症

最高研发阶段(中国)批准上市

特殊审评突破性疗法 (美国)、优先审评 (中国)、突破性疗法 (中国)、优先审评 (美国)

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序列信息

Sequence Code 190619L

来源: *****

Sequence Code 190621H

来源: *****

关联

18

项与多奈单抗相关的临床试验

NCT06566170 / RecruitingN/A

Long-Term Real-World Comparative Effectiveness of Donanemab Plus Usual Care Versus Usual Care Alone in US Patients With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-REAL US)

The main purpose of this study is to evaluate the long-term effectiveness of donanemab plus usual care versus usual care alone in participants with early symptomatic AD. The study will employ a prospective, observational cohort design with participant management resembling real-world practice to the greatest extent possible via prospective assessments and linkage to historical and prospective electronic health records. The study will last about 273 weeks and may include up to 28 visits.

开始日期2024-10-07

申办/合作机构

Eli Lilly & Co.

NCT05738486 / Active, not recruiting临床3期

Investigating the Effect of Different Donanemab Dosing Regimens on ARIA-E and Amyloid Lowering in Adults With Early Symptomatic Alzheimer's Disease

This study will investigate different donanemab dosing regimens and their effect on the frequency and severity of ARIA-E in adults with early symptomatic Alzheimer's disease (AD) and explore participant characteristics that might predict risk of ARIA.

开始日期2023-02-28

申办/合作机构

Eli Lilly & Co.

NCT05508789 / Recruiting临床3期

Global Study to Investigate Safety and Efficacy of Donanemab in Early Symptomatic Alzheimer's Disease

The reason for this study is to assess the safety and efficacy of donanemab in participants with early Alzheimer's disease. The study duration including screening and follow-up is up to 93 weeks.

开始日期2022-10-10

申办/合作机构

Eli Lilly & Co.

100 项与多奈单抗相关的临床结果

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100 项与多奈单抗相关的转化医学

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100 项与多奈单抗相关的专利（医药）

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134

项与多奈单抗相关的文献（医药）

2025-01-01·NEUROSCIENCE

Comparison of the efficacy of updated drugs for the treatment on the improvement of cognitive function in patients with Alzheimer ’s disease: A systematic review and network meta- analysis

Review

作者: Guo, Kun ; Li, Rong ; Liu, Zhiqin ; Xi, Jing ; Sun, Fanya ; Di, Zhengli ; Zhao, Hongwei ; Gu, Naibing ; Cao, Weili ; Jia, Xiaotao ; Chang, Hongye ; Zhu, Bo ; Shen, Jia ; Ding, Le

BACKGROUND:

The recent emergence of updated drugs for the treatment of Alzheimer's disease (AD) has produced encouraging cognitive and clinical results in clinical trials, but there is still controversy over how to choose effective treatment options among these numerous drugs. The purpose of this network meta-analysis (NMA) is to compare and rank these drugs based on their efficacy.

METHODS:

We systematically searched in PubMed, Web of Science databases and Cochrane LIbrary, gov for randomized controlled trials for data from 2020 to 2024, and then performed a random-effect network meta-analysis.

RESULTS:

Our NMA results showed that in several main indicators ADAS-cog, CDR-SB and ADCS-ADL. GV-971 (MD -2.36, 95 % CI -5.08, 0.35), Lecanemab (MD -2.00, 95 % CI -5.25, 1.26), Donanemab (MD -1.45, 95 % CI -4.70, 1.81), Masupirdine (MD -0.83, 95 % CI -3.49, 1.84) were more effective than placebo in improving ADAS-cog. In terms of CDR-SB, Lecanemab (MD -3.11,95 % CI -5.23, -0.99) was more effective. Compared with placebo, Donanemab was more effective in ADCS-ADL (MD 3.26,95 % CI 1.48,5.05). SUCRA values showed that GV-971 (76.1 % and 68.7 %) could achieve better therapeutic effects in ADAS-cog) and NPI, and Lecanema (98.1 %) was more effective in improving CDR-SB scores than other drugs. Donanemab (99.8 %) may be the most promising way to slow down the decline in ADCS-ADL scores. The effect of Masupirdine (80.7 %) on MMSE was significantly better than that of several other drugs.

CONCLUSION:

Donanemab and Lecanemab showed good efficacy in ADCS-ADL and CDR-SB, respectively. GV-971 is the best choice to improve ADAS cogs and NPI.

2025-01-01·AGEING RESEARCH REVIEWS

Disease-modifying therapies for Alzheimer’s disease: Clinical trial progress and opportunity

Review

作者: Zhang, Yujie ; Luo, Shilin ; Jiao, Bin ; Chen, Jie ; Li, Yanru

The U.S. Food and Drug Administration (FDA) recently approved lecanemab and donanemab for the treatment of early symptomatic Alzheimer's disease (AD) after their phase III trials reached endpoints. These two anti-amyloid β monoclonal antibodies represent the latest promise of disease-modifying therapy (DMT) for AD, which undoubtedly reignites new hope for DMTs to combat the staggering financial and human costs of AD. However, in addition to these two successful antibodies, there have been enormous efforts to develop DMTs in various aspects to meet the therapeutic requirement of AD. In this review, we delineate the core principles and methodologies of diverse DMTs, covering the advances in clinical trials of drug candidates that either have been discontinued, completed, or are ongoing, as well as brain stimulation and lifestyle interventions. In addition, by overseeing the fate of various candidate molecules, we hope to provide references and ideas for prospective approaches and promising applications of DTMs for AD, particularly in terms of universality and clinical application economics, to optimize efficacy and maximize AD patient benefits in the future.

2024-12-31·mAbs

Single domain antibody-scFv conjugate targeting amyloid β and TfR penetrates the blood–brain barrier and interacts with amyloid β

Article

作者: Eriksson, Jonas ; Sjöström, Elisabet O. ; Sehlin, Dag ; Dallas, Tiffany ; Berglund, Magnus M. ; Syvänen, Stina ; Faresjö, Rebecca

Neurodegenerative diseases such as Alzheimer's disease (AD) pose substantial challenges to patients and health-care systems, particularly in countries with aging populations. Immunotherapies, including the marketed antibodies lecanemab (Leqembi®) and donanemab (Kisunla^TM), offer promise but face hurdles due to limited delivery across the blood-brain barrier (BBB). This limitation necessitates high doses, resulting in increased costs and a higher risk of side effects. This study explores transferrin receptor (TfR)-binding camelid single-domain antibodies (VHHs) for facilitated brain delivery. We developed and evaluated fusion proteins (FPs) combining VHHs with human IgG Fc domains or single-chain variable fragments (scFvs) of the anti-amyloid-beta (Aβ) antibody 3D6. In vitro assessments showed varying affinities of the FPs for TfR. In vivo evaluations indicated that specific VHH-Fc and VHH-scFv fusions reached significant brain concentrations, emphasizing the importance of optimal TfR binding affinities. The VHH-scFv fusions were further investigated in mouse models with Aβ pathology, showing higher retention compared to wild-type mice without Aβ pathology. Our findings suggest that these novel VHH-based FPs hold potential for therapeutic and diagnostic applications in AD, providing a strategy to overcome BBB limitations and enhance brain targeting of antibody-based treatments. Furthermore, our results suggest that a given bispecific TfR-binding fusion format has a window of "optimal" affinity where parenchymal delivery is adequate, while blood pharmacokinetics aligns with the desired application of the fusion protein.

938

项与多奈单抗相关的新闻（医药）

2024-12-19

·Endpoints

Bristol Myers pays $100M upfront to collaborate with Leqembi originator in Alzheimer's

Bristol Myers Squibb is partnering with the original developer of Leqembi in a new Alzheimer’s disease deal. The large drugmaker said Thursday that it’s giving BioArctic $100 million upfront to license two programs called BAN1503 and BAN2803. The Stockholm-based biotech can earn up to $1.25 billion in milestones. The deal fits into Bristol Myers’ emerging neuroscience strategy in the wake of its recently approved schizophrenia drug Cobenfy, which it acquired in a $14 billion buyout of Karuna Therapeutics. BMS has two other Alzheimer’s drugs in its pipeline, and it’s also testing Cobenfy in Alzheimer’s-related psychosis. Both experimental drugs from the BioArctic partnership target “a specific truncated, pyroglutamate modified form of amyloid-beta,” according to a press release. It’s a similar method to attempt to treat Alzheimer’s as Eli Lilly’s Kisunla and a program from Aliada Therapeutics, which AbbVie acquired for $1.4 billion in October. Additionally, BAN2803 is designed to use one of BioArctic’s newer technologies called “BrainTransporter,” aiming for better drug penetration across the blood-brain barrier. These kinds of therapies for Alzheimer’s have become a buzzy topic in recent years; Lilly, AbbVie and Eisai all have licenses for such tech, while Roche developed its own in-house . The Roche program, called trontinemab, read out early-stage results in October. It has not yet outlined next steps.

并购

2024-12-19

·echemi

Eli Lilly's Donanemab Injection Approved for Market, New Breakthrough in Alzheimer's Treatment

On December 18, Eli Lilly announced that its developed Donanemab injection has received approval from the drug regulatory authority and is officially on the market. This medication is approved for treating adults with mild cognitive impairment and mild dementia due to Alzheimer's disease. Eli Lilly revealed on its official Weibo account that Donanemab injection is currently the only clinically supported targeted amyloid therapy that can cease medication after clearing amyloid plaques. This therapy helps alleviate the treatment burden on patients by reducing the frequency of infusions and lowering treatment costs. The approval from the drug regulatory authority is primarily based on data from the Phase III TRAILBLAZER-ALZ 2 clinical study (NCT04437511). This study aimed to evaluate the safety and efficacy of Donanemab injection in patients with early symptomatic Alzheimer's disease, particularly those with confirmed Alzheimer's neuropathological changes. The trial combined cognitive assessments with pathological evidence of Alzheimer's and enrolled 1,736 subjects from eight countries. Results from the TRAILBLAZER-ALZ 2 study indicated that the effects of Donanemab injection are more pronounced in patients at earlier stages of the disease. During the 18-month trial period, subjects were divided into two groups for analysis: one group consisted of patients in the earlier stages of the disease (with low to moderate levels of tau protein), while the other group included the overall population, comprising subjects with low, moderate, and high tau levels. The study demonstrated that treatment with Donanemab injection significantly slows clinical decline in both groups. In the population with earlier disease progression, patients treated with Donanemab injection experienced a 35% slower decline in memory, thinking, and daily functioning, as measured by the Integrated Alzheimer's Disease Rating Scale (iADRS), compared to those receiving a placebo. In the overall population, treatment significantly slowed clinical decline by 22%. Among both groups, subjects treated with Donanemab injection exhibited up to a 39% reduced risk of progressing to the next clinical stage compared to those receiving a placebo.

临床结果临床3期上市批准临床2期

2024-12-18

·摩熵医药

礼来重磅阿尔默兹海默症1类新药在中国获批上市！

注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需要得到授权。 12月18日，礼来宣布，该公司1类新药donanemab注射液上市申请已获得NMPA批准，用于治疗成人因阿尔茨海默病（AD）引起的轻度认知功能障碍和阿尔茨海默病轻度痴呆。截图来源：礼来 Donanemab是一种用于静脉输注的药物，每四周注射一次。该产品已经于2024年7月获美国FDA率先批准，用于治疗出现早期症状的阿尔茨海默病成年人（商品名：Kisunla）。在美上市仅 5 个月后，全球第二款 AD 新药登陆中国，同时它也是第一款且唯一一款有证据支持，在清除淀粉样蛋白斑块后可停药的靶向淀粉样蛋白的疗法。截图来源：摩熵医药全球药物研发数据库该药此前入选了行业媒体Evaluate选出的“2024年十大潜在重磅研发管线”榜单。此外，礼来此前新闻稿表示，donanemab是首个有证据表明在淀粉样斑块清除后可停止治疗的淀粉样斑块靶向疗法，因此预计该疗法可以降低治疗成本并减少输液次数。 2023年7月，礼来公司正式揭晓了其III期研究的全面数据，这些数据表明，针对早期症状性阿尔茨海默病（AD）患者，该公司研发的药物能明显延缓其认知及功能上的衰退速度。 clinicaltrials.gov 截图 2024年10月，礼来再次传来喜讯，其TRAILBLAZER-ALZ 6临床3b期研究已成功达到主要试验目标。在为期24周的试验中，采用优化后的donanemab给药方案，早期症状性AD成年患者发生水肿/渗出相关的淀粉样蛋白相关成像异常（ARIA-E）的风险显著降低，相较于标准给药方案，风险降低幅度达到了41%。值得注意的是，在携带载脂蛋白E（APOE4）纯合子——这一已知的阿尔茨海默病高风险遗传因子——的患者中，优化方案的效果更为显著，ARIA-E的相对风险降低了67%。同时，优化后的给药方案在清除患者脑内的淀粉样蛋白斑块和降低血浆P-tau217水平方面，与标准方案的效果相当。礼来公司计划将这些重要数据提交至全球各大监管机构，以期对donanemab的药物标签进行更新。 clinicaltrials.gov 截图在中国市场，礼来也在积极推进donanemab的研发进程。此前，该公司已完成了一项针对中国健康受试者的donanemab1期研究，评估了其安全性、耐药性和药代动力学特性。2022年9月，礼来又启动了TRAILBLAZER-ALZ 5国际多中心、随机、双盲、安慰剂对照3期研究，这是一项在中国和韩国进行的针对早期症状性阿尔茨海默病的注册试验，旨在评估donanemab在存在脑tau蛋白病理的早期症状性阿尔茨海默病患者中的安全性和有效性。目前，该研究正在进行中，并计划在中国招募400名受试者。据公开资料显示，除了礼来的donanemab注射液外，还有多款针对阿尔茨海默病的新药正在中国进行临床研究，这些药物的作用机制各不相同，包括乙酰胆碱酯酶抑制剂、M1/M4毒蕈碱乙酰胆碱受体激动剂、抗β淀粉样蛋白（Aβ）抗体、靶向Aβ的小分子新药以及TAAR1/5-HT2CR双靶点激动剂等。 END 近期热门资源获取后台回复关键词“深度报告”，获取价值18600元，报告大礼包后台回复关键词“2023首仿”，获取2023年首仿药物获批名单后台回复“GLP-1深度报告”，获取完整《GLP-1产业现状与未来发展》PDF版。后台回复“中国 I 类新药”，获取完整《中国 I 类新药靶点》PDF版。后台回复“NAFLD/NASH”，获取完整《NAFLD/NASH报告》PDF版。后台回复“AI+制药”，获取完整《中国AI制药企业白皮书》PDF版。后台回复“XXG”，获取完整《中国心血管系统药物分析报告》PDF版。后台回复“FZZJ”，获取完整《基于剂型改良的复杂注射剂分析》PDF版。后台回复“药品进出口”，获取完整《中国药品进出口白皮书》深度报告-PDF版。联系我们，体验摩熵医药更多专业服务会议合作园区服务数据库咨询定制服务媒体合作 👆👆👆点击上方图片，即可开启摩熵化学数据查询点击阅读原文，申请摩熵医药企业版免费试用！

临床3期临床结果上市批准

100 项与多奈单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11500	多奈单抗	-	-

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
阿尔茨海默病引起的痴呆症	英国	Eli Lilly Nederland BV	2024-10-23
阿尔茨海默病引起的痴呆症	英国	Eli Lilly & Co.	2024-10-23
轻度认知障碍	英国	Eli Lilly Nederland BV	2024-10-23
轻度认知障碍	英国	Eli Lilly & Co.	2024-10-23
阿尔茨海默症	美国	Eli Lilly & Co.	2024-07-02

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
精神障碍	申请上市	加拿大	Eli Lilly Canada, Inc.	-
行为障碍	临床3期	美国	Eli Lilly & Co.	2023-02-28
行为障碍	临床3期	英国	Eli Lilly & Co.	2023-02-28
神经认知障碍	临床3期	阿根廷	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	澳大利亚	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	比利时	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	捷克	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	法国	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	德国	Eli Lilly & Co.	2022-10-10
神经认知障碍	临床3期	荷兰	Eli Lilly & Co.	2022-10-10

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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


NCT05738486 (TRAILBLAZER-ALZ 6, Company_Website) 人工标引	临床3期	阿尔茨海默症	843	received two vials (700 mg) of donanemab for the first three infusions, then four vials (1400 mg) thereafter (Standard Dosing Regimen)	顧襯築鹽鹽製選蓋繭鑰(構鹽願壓壓壓製網糧鹽) = 醖鬱壓淵顧築繭艱艱鬱獵醖膚夢膚鏇膚襯鏇鏇 (網積衊範網壓艱窪廠觸 ) 更多	积极	2024-10-29
				received 1 vial (350 mg) of donanemab for the first infusion, two vials (700 mg) for the second infusion, three vials (1,050 mg) for the third infusion, and four vials (1400 mg) per infusion thereafter (Modified Titration)	顧襯築鹽鹽製選蓋繭鑰(構鹽願壓壓壓製網糧鹽) = 積衊繭願範積願顧鬱製獵醖膚夢膚鏇膚襯鏇鏇 (網積衊範網壓艱窪廠觸 ) 更多
NCT05567159 (CTgov)	临床1期	-	42	Donanemab	鏇製鏇壓遞鑰膚廠積鹹(襯鬱鏇獵願鏇齋鹽願願) = 遞醖淵製簾積廠觸衊鹽鑰鬱鬱築鏇齋壓願鑰蓋 (窪夢窪鑰蓋鬱網夢製遞, 糧鬱窪觸鏇築鹹遞醖壓 ~ 夢鬱鑰遞簾餘壓積夢鏇) 更多	-	2024-10-04
NCT05533411 (CTgov)	临床1期	-	36	Placebo (Placebo)	網膚鏇糧獵鹹遞構顧鹹(醖淵範壓膚蓋積壓繭觸) = 繭鏇顧襯觸鏇襯糧鏇醖夢淵艱窪醖鏇願艱選顧 (襯顧壓願憲遞淵鹹糧積, 製鬱廠鹽構觸鏇艱壓膚 ~ 艱願製構糧蓋淵製廠積) 更多	-	2024-10-04
				Donanemab (700 mg Donanemab)	網膚鏇糧獵鹹遞構顧鹹(醖淵範壓膚蓋積壓繭觸) = 餘壓簾積淵遞鹹窪網範夢淵艱窪醖鏇願艱選顧 (襯顧壓願憲遞淵鹹糧積, 憲鏇艱膚鬱醖蓋憲醖夢 ~ 繭積衊糧蓋鏇膚顧願憲) 更多
NCT01837641 (CTgov)	临床1期	阿尔茨海默症 \| 认知功能障碍	63	Placebo (Placebo IV)	構觸築願憲鑰憲鏇齋簾(簾鑰願積鏇築範鏇糧膚) = 窪願鑰鏇選鑰糧網鬱淵鹽糧網壓遞廠艱夢醖選 (鏇餘襯糧蓋網蓋獵齋糧, 選範蓋餘鹹鏇夢壓繭餘 ~ 壓顧鏇壓製願網獵壓獵) 更多	-	2024-10-04
				LY3002813 (0.1 mg/kg / 0.3 mg/kg LY3002813 IV)	構觸築願憲鑰憲鏇齋簾(簾鑰願積鏇築範鏇糧膚) = 壓範淵鑰獵蓋壓願鏇積鹽糧網壓遞廠艱夢醖選 (鏇餘襯糧蓋網蓋獵齋糧, 鏇願遞構積願廠顧鬱艱 ~ 廠築獵衊壓顧夢鏇鹹獵) 更多
NCT04437511 (FDA_CDER) 人工标引	临床3期	阿尔茨海默症	1,736	KISUNLA	夢簾醖蓋淵鏇窪齋艱膚(構醖顧窪鹽鹹醖築選鏇): Difference = 2.92, P-Value = <0.0001 更多	积极	2024-07-02
				Placebo
NCT04437511 \| NCT03367403 (TRAILBLAZER-ALZ \| TRAILBLAZER-ALZ2, AAN2024)	临床2/3期	number of microhemorrhages \| cortical superficial siderosis \| mean arterial pressure ... 更多	2,031	Donanemab	鏇積醖艱蓋製鑰遞夢願(窪餘獵糧淵簾鏇範憲憲) = 願艱蓋蓋繭範構構壓憲糧廠膚簾衊艱願構襯壓 (壓鑰網積築糧製範選憲 )	积极	2024-04-09
NCT04437511 (TRAILBLAZER-ALZ 2, Pubmed) 人工标引	临床3期	阿尔茨海默症	1,736	donanemab	願製壓觸糧窪獵鑰衊窪(艱醖膚壓壓餘壓蓋憲範) = 構製網顧觸顧構壓鏇製餘窪艱餘鏇衊網簾範鹽 (壓製範衊製積衊糧獵衊, -7.01 ~ to 5.03) 达到更多	积极	2023-07-17
				placebo	願製壓觸糧窪獵鑰衊窪(艱醖膚壓壓餘壓蓋憲範) = 積網遞範築餘齋顧鏇餘餘窪艱餘鏇衊網簾範鹽 (壓製範衊製積衊糧獵衊, -10.23 ~ to 8.31) 达到更多
TRAILBLAZER-ALZ-4 (AAN2023)	临床3期	阿尔茨海默症	148	Donanemab	遞範鬱艱膚齋膚艱鬱艱(艱襯鏇網積鏇簾襯鏇鹹) = 62.0% of donanemab-treated and 66.7% of aducanumab-treated participants reported an adverse event (AE), there were no serious AEs due to ARIA in donanemab arm and 1.4% serious AEs (one event) due to ARIA were reported in aducanumab arm. 觸網構鏇淵廠衊觸獵蓋 (鏇繭範衊膚鬱襯鬱網鹽 )	-	2023-04-25
				Aducanumab
NCT05108922 (TRAILBLAZER-ALZ 4, Corporate Publications) 人工标引	临床3期	阿尔茨海默症	130	Donanemab	夢觸蓋願積餘構觸醖齋(艱餘醖積鹹鹽窪夢膚選) = 廠蓋廠簾網醖憲鏇醖鏇齋鏇鹽鏇選鹹範醖蓋憲 (積願鹹鹽醖網願醖顧積 ) 更多	优效	2022-11-30
				Aducanumab-avwa-avwa	夢觸蓋願積餘構觸醖齋(艱餘醖積鹹鹽窪夢膚選) = 糧顧膚製夢淵願製製遞齋鏇鹽鏇選鹹範醖蓋憲 (積願鹹鹽醖網願醖顧積 ) 更多
NCT03367403 (TRAILBLAZER-ALZ, CTgov)	临床2期	阿尔茨海默症	272	Donanemab (Donanemab Monotherapy (Donanemab-M))	窪醖淵膚鑰鬱鏇壓積鹹(遞鹹襯醖糧膚襯廠廠餘) = 繭範獵衊廠醖餘築鏇廠鹹選遞廠繭築醖壓窪鹹 (齋壓餘壓窪膚夢積窪膚, 積獵餘築夢簾壓憲艱築 ~ 膚鹹壓鑰膚鹽衊構鏇壓) 更多	-	2022-02-15
				Placebo (Placebo)	窪醖淵膚鑰鬱鏇壓積鹹(遞鹹襯醖糧膚襯廠廠餘) = 網襯淵鏇遞醖壓範淵網鹹選遞廠繭築醖壓窪鹹 (齋壓餘壓窪膚夢積窪膚, 艱鹽築鑰鹹窪蓋鬱壓夢 ~ 鏇網膚構蓋構繭蓋製糧) 更多