Efficacy and Safety of Co-administered Cagrilintide and Semaglutide (CagriSema) 1.0 mg/1.0 mg s.c. Once Weekly Versus Tirzepatide 5 mg s.c. Once Weekly in Participants With Type 2 Diabetes Inadequately Controlled on Metformin, SGLT2 Inhibitor or Both

This study will look at how much CagriSema lowers blood sugar and body weight in people with type 2 diabetes. CagriSema is a new investigational medicine. Doctors cannot yet prescribe CagriSema. CagriSema will be compared to a medicine called tirzepatide. Doctors can prescribe tirzepatide in some countries. Participants will either receive CagriSema or tirzepatide. Which treatment the participant will receive is decided by chance. For each participant, the study will last for up to 1 year and 4 months.

开始日期2024-11-05

申办/合作机构

Novo Nordisk A/S

CTR20241846 / Recruiting临床3期

2型糖尿病受试者在每日一次基础胰岛素伴或不伴二甲双胍的基础上加用cagrilintide和司美格鲁肽（CagriSema）2.4 mg/2.4 mg和1.0 mg/1.0 mg皮下每周一次复方制剂与安慰剂相比的有效性和安全性

本研究将观察CagriSema帮助2型糖尿病患者降低血糖和体重的效果。

开始日期2024-07-08

申办/合作机构

诺和诺德（中国）制药有限公司

[+1]

NCT06388187 / Active, not recruiting临床3期

Efficacy and Safety of Cagrilintide s.c. in Combination With Semaglutide s.c.(CagriSema s.c. 1.0 mg/1.0 mg and 1.7 mg/1.7 mg) Once-weekly in Participants With Overweight or Obesity

This study will look at how well CagriSema helps people with excess body weight lose weight. CagriSema is a new medicine developed by Novo Nordisk that combines cagrilintide and semaglutide. CagriSema cannot yet be prescribed by doctors. In the study, participant will either get CagriSema or dummy medicine and which treatment participant get is decided by chance. The study will last for about 1½ years for each participant.

开始日期2024-06-24

申办/合作机构

Novo Nordisk A/S

100 项与 CagriSema 相关的临床结果

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100 项与 CagriSema 相关的转化医学

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100 项与 CagriSema 相关的专利（医药）

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1,227

项与 CagriSema 相关的文献（医药）

2024-10-01·Current diabetes reviews

Future is Brighter: New Potential Paradigm-Shifting Medications and Regimens for Diabetes and Obesity

Review

作者: Aliter, Hashem F. ; Al-Horani, Rami A. ; Aliter, Kholoud F.

Abstract::

Diabetes is a chronic illness that can become debilitating owing to its microvascular and macrovascular complications. Its prevalence is increasing and so is its cost. Diabetes, particularly type 2, appears to have a very close relationship with obesity. While lifestyle modifications, exercises, and current therapeutics have substantially improved clinical outcomes, the need for new therapeutics and regimens continue to exist. Several new medications and regimens for diabetes, obesity, and diabesity are showing promising results in advanced clinical trials. For type 1 diabetes mellitus (T1DM), they include teplizumab, ustekinumab, jakinibs, and cell therapies, whereas for type 2 diabetes mellitus (T2DM), they include once-weakly insulin, tirzepatide, high oral dose of semaglutide, orforglipron, retatrutide, CagriSema, and survodutide. Given their structural and mechanistic diversity as well as their substantial efficacy and safety profiles, these medications and regimens are paradigm shifting and promise a brighter future. They will likely enable better disease prevention and management. This review will provide details about each of the above strategies to keep the scientific community up to date about progress in the fields of diabetes and obesity

2024-07-01·Hepatology research : the official journal of the Japan Society of Hepatology

Hepatitis B surface antigen glycan isomer is a predictor of the development of hepatocellular carcinoma during nucleoside/nucleotide analog therapy

Article

作者: Kawada, Norifumi ; Kozuka, Ritsuzo ; Fujii, Hideki ; Hagihara, Atsushi ; Odagiri, Naoshi ; Kotani, Kohei ; Yukawa‐Muto, Yoshimi ; Motoyama, Hiroyuki ; Kawamura, Etsushi ; Enomoto, Masaru ; Uchida‐Kobayashi, Sawako

Abstract:

Aim:

A recombinant monoclonal antibody against the hepatitis B surface antigen glycan isomer (HBsAgGi) was newly developed using the O‐glycosylated PreS2 peptide in M‐HBsAg of hepatitis B virus (HBV) genotype C. However, the association between HBsAgGi and the development of hepatocellular carcinoma (HCC) during nucleoside/nucleotide analog (NA) therapy remains unknown.

Methods:

A total of 112 HBV genotype C‐infected patients who were treated with NA were included in this study. We assessed the association between HBV markers, including HBsAgGi and other conventional markers, and the development of HCC during NA therapy.

Results:

Ten patients developed HCC during the follow‐up period. Of the HBV markers, HBsAg (≤3.53 log IU/mL; p = 0.047), HBsAgGi/HBsAg ratio (≥1.10; p = 0.035), and HBV DNA (≤6.3 log copies/mL; p = 0.012) at baseline and HBsAg (≤3.19 log IU/mL; p = 0.033) and HBsAgGi/HBsAg ratio (≥1.09; p = 0.003) at 48 weeks after NA therapy were significantly associated with the development of HCC according to the log rank test. In contrast, no significant association was observed between HBsAgGi and the development of HCC. Multivariate analysis revealed that a platelet count at baseline ≤88 × 103/mm3 (p = 0.026; hazard ratio [HR], 10.577) and an HBsAgGi/HBsAg ratio at 48 weeks after NA therapy ≥1.09 (p = 0.040; HR, 10.099) were independently and significantly associated with the development of HCC.

Conclusions:

Our findings suggest that a combination of on‐treatment HBsAgGi and HBsAg predicts the development of HCC during NA therapy.

2024-07-01·Hepatology research : the official journal of the Japan Society of Hepatology

Risk of hepatocellular carcinoma after curative treatment when switching from tenofovir disoproxil fumarate or entecavir to tenofovir alafenamide: A real‐world multicenter cohort study

Article

作者: Lee, Yun Bin ; Shin, Hyunjae ; Yoon, Jung-Hwan ; Park, Youngsu ; Sinn, Dong Hyun ; Kim, Yoon Jun ; Ko, Yunmi ; Cho, Eun Ju ; Song, Byeong Geun ; Kim, Seung Up ; Lee, Jeong-Hoon ; Park, Jeayeon ; Yu, Su Jong ; Hur, Moon Haeng

Abstract:

Aim:

Antiviral treatment reduces the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. However, there is a lack of high‐quality evidence regarding the preventive effects of tenofovir alafenamide (TAF) on HCC. We evaluated the impact of TAF use after curative treatment on HCC recurrence.

Methods:

Patients who underwent surgery or radiofrequency ablation as a curative treatment for HCC were selected. Those patients who continued antiviral treatment with nucleos(t)ide analogs (NAs; entecavir [ETV] or tenofovir disoproxil fumarate [TDF]) or switched to TAF were included. The primary outcome was HCC recurrence, and the time‐varying effect of NA use on HCC recurrence was analyzed using various statistical methods.

Results:

Among 2794 consecutive patients with chronic hepatitis B who received curative treatment for HCC, 199 subsequently switched from ETV or TDF to TAF. After a median of 3.0 years, 1303 patients (46.6%) experienced HCC recurrence. After propensity score matching (ratio 1:10), switching to TAF was not associated with an increased HCC recurrence (HR 1.00, 95% CI 0.68–1.47; p = 1.00) by time‐varying Cox analysis. Switching to TAF was not associated with HCC recurrence in subgroups of NA (HR 1.06, 95% CI 0.67–1.67; p = 0.81 for TDF, and HR 1.09, 95% CI 0.51–2.33; p = 0.82 for ETV). Kaplan–Meier analysis showed comparable HCC recurrence‐free survival between patients who switched to TAF and those who continued with their NA (p = 0.08). Time‐varying Cox analyses in various subgroups confirmed the primary findings.

Conclusions:

TAF is as effective as TDF and ETV in preventing HCC recurrence after curative treatment.

203

项与 CagriSema 相关的新闻（医药）

2024-11-07

·空之客

【医苑观畴】2024年三季度海外药企进展更新：诺和诺德NVO

1 整体表现 NVO今年以来的业绩和股价走势呈现显著背离，特别是这个季度收入跨过$10b大关、但市值迅速滑落到$500b以下，这其实代表性地反映了近期市场在GLP-1话题上正在经历祛魅的过程。前九个月收入同比增长23%，净利润同比增长19%（这还是考虑到从KBP引进Ocedurenone的减值损失之后），对于其他大药企而言简直是逆天的增长，但相比市场对NVO的预期而言明显并不能让人满意，以及跌了这么多之后依然35x的市盈率。基于这种预期，公司在最后一个季度并没有上调全年指引，2024年收入增速的中位预期仍在25%，而2025年有可能降到15-20%之间。 2 已上市产品从上个季度开始，我们就已经隐约感觉到GLP-1增长天花板开始若隐若现（参见NVO二季报分析和LLY二季报分析）；到这个季度T药突然出现的增长停滞（参见LLY三季报分析），更急剧加重了这种提前滞涨的担心，于是S药的表现就至关重要，到底是NVO成功抵御了LLY的市场份额冲击、还是GLP-1整体的渗透放缓，是这个季度全行业瞩目的话题。首先最笼统直观的是S药在连续走平两个季度之后重新恢复环比增长，而对手T药则环比陷入停滞（即使对存货影响进行调整后也就是$4.6b，调整逻辑亦参见LLY三季报分析）。然而将S药和T药加总也不难发现，24Q3的环比增速已经滑落到10%以内、24Q3比23Q4也只增加了约30%，也就意味着今年以来整个GLP-1市场的二阶导在急速回落，从绝对值来看S药和T药目前LTM累计分别是$27.1b和$13.4b，如果就此进入增速拐点则与此前星辰大海的预期相去甚远。这种增速放缓的预期，也能从公司季报里的这张全球GLP-1使用者人数的图里有所反映（顺便一说这张图是第一次出现在NVO季报里，总给人一种要给GLP-1盖棺定论的色彩）。在T2D领域，见顶的信号进一步被坐实，无论是美国还是国际市场，GLP-1的总处方量走平、新处方量下滑，特别是在新处方量上S药下滑的情况下、T药并没有抢到更多，而两家公司的所谓产能瓶颈问题又都已经有显著缓和（毕竟上个季度就已经从FDA短缺药品清单上拿掉了），只能解释为在T2D这个适应症的渗透率已经快看到头了。当然后续或许还能通过CKD/PAD等新增适应症在往上拱一拱，但应该对大数量级不会有根本性的改变。在减肥领域，面对跟T2D类似、但应该更早期的迹象，即虽然总处方量还在增加，但S药新处方量回落、但T药却病没有显著增加，整个减肥市场增长的二阶导被限制住了，且NVO相比LLY在这个市场的优势已经不大。就这个季度而言，Wegovy看起来环比34%的增长依然生猛，但这里面美国市场的环比增速已经回落到25%以下、主要依靠国际市场，而且公司在电话会上明确说这一高速增长与国际市场上市铺货导致的存货增加有关、可能是一次性的（是不是想到了上个季度的T药、以及这至少说明Wegovy确实已经不存在产能瓶颈），这就让人进一步担心GLP-1减肥的增速下滑是不是有可能滞后T2D几个季度就会出现。在GLP-1光芒之下，NVO传统业务胰岛素就有点乏善可陈，目前的长效、短效、预混等胰岛素也就能把年销售额稳定在$7.5b左右，刚在欧洲获批的Icodec目前尚未贡献规模销售。生长激素和凝血因子也都很难贡献多少增量，特别是在近年来公司产能严重短缺的情况下。 3 在研管线对于Sema来说，本季度最重要的进展是治疗NASH的三期临床ESSENCE试验中的72周病理结果，Sema与安慰剂相比纤维化终点的响应率是37.0% vs 22.5%、NASH终点的响应率是62.9% vs 34.1%，两个终点都有显著性，看起来既无惊喜、也无惊吓，但至少很难形成对其他NASH药物的碾压级优势（具体分析参见【药海听涛】全拿下，一扫光：GLP-1真的会杀死NASH市场吗？）然后就是口服剂型在9,650例T2D患者的三期临床SOUL研究中，将主要心血管事件MACE风险降低14%，预计将在年底提交该适应症的上市申请。从Inversago收购来的CB1激动剂Monlunabant终于公布了Ph2a数据，在给药16周后，每日一次10mg的Monlunabant与安慰剂相比体重降幅为7.1 vs 0.7kg（基线110.1kg），而更高的20/50mg剂量对体重降幅增加有限，这与之前预期的15%降幅差距明显。除此以外，值得关注的进展还包括：Sema公布治疗外周动脉疾病的T2D患者的三期临床STRIDE试验的积极结果，IcoSema向欧盟提交上市申请，Amycretin启动二期临床，新增每周一次长效制剂Amylin355和治疗A型血友病的口服抗体片段Inno8进入一期临床。后续值得期待的重要节点包括：Sema的CKD适应症获批、HFpEF适应症重新提交上市申请、NASH适应症提交上市申请、口服剂型的CVOT适应症提交上市申请，CagriSema的两个三期临床结果。从NVO和LLY近几个季度的表现来看，Ozempic和Mounjaro都已经明显走平，Wegovy和Zepbound也已经出现新处方量的下滑，这不能不增加我们对整个GLP-1市场空间提前见顶的担忧，诚然后续还有CKD、HF、NASH等适应症的扩容潜力，但在T2D和Obesity这两大最重要基本盘上低于预期，那对整个GLP-1的信心有可能造成重挫。目前K药与S药的LTM累计销售额分别是$28.3b vs $27.1b，曾经市场都在调侃K药和S药谁的药王宝座坐得最短，然而现在可能连S药能否坐的上去都可能存疑了。

财报临床研究

2024-11-06

·药智网

司美格鲁肽大卖203亿美元！

11月6日，诺和诺德发布2024年第三季度报，今年前9个月，销售额增长了23%，达到2047亿丹麦克朗，其中糖尿病和肥胖症治疗药物的销售额增长了25%，达到1918亿丹麦克朗。明星产品司美格鲁肽（Semaglutide）继续高歌猛进，3个品牌（降糖针剂Ozempic，降糖片剂Rybelsus，和减肥针剂Wegovy）今年前9个月销售额达到1412.13亿丹麦克朗，约203亿美元。数据来源：诺和诺德财报不久前，礼来也公布了其业绩，其中GIPR/GLP-1R双重激动剂Tirzepatide（替尔泊肽）2个品牌（降糖针剂Mounjaro，减肥针剂Zepbound）在今年前三个季度销售额达到110.284亿美元。具体来看，Mounjaro销售收入80.10亿美元，Zepbound销售收入30.18美元。 Zepbound去年11月份上市以来放量迅速，累计处方患者超过60万人。图片来源：礼来司美格鲁肽和替尔泊肽两款药物在今年都实现了销售额大幅增长，而且两大制药巨头还在探索GLP-1R药物其他适应症，或许新的惊喜已在酝酿中。就在几天前，诺和诺德公布了ESSENCE关键临床3期试验第1部分的主要结果。分析显示，司美格鲁肽（Wegovy）与安慰剂相比，可显著缓解代谢功能障碍相关脂肪性肝炎（MASH）患者的肝纤维化并实现脂肪性肝炎消退，实现了其主要终点。在第72周，接受2.4 mg司美格鲁肽治疗的患者中，37.0%的人肝纤维化得到改善，脂肪性肝炎没有恶化；而接受安慰剂治疗的患者中，这一比例为22.5%。接受2.4 mg司美格鲁肽治疗的患者中，62.9%的人脂肪性肝炎得到缓解，肝纤维化没有恶化，而接受安慰剂治疗的患者中，这一比例为34.1%。相比其他MASH新药，司美格鲁肽在肝纤维化改善数据方面表现并不算优秀，但这次研究至少证明了GLP-1R靶点确实有改善纤维化的潜力，意味着GLP-1R药物在治疗MASH领域迈出了具有重要意义的一步。诺和诺德预计将于2025年上半年向美国和欧盟监管单位递交Wegovy用于治疗MASH的监管申请。该试验第2部分将继续进行，预计于2029年公布结果。 01 新一代减肥药酝酿中司美格鲁肽和替尔泊肽的成功打破了多年来肥胖赛道无好药可用的僵局，但这两款药物也并非完美无缺，例如需要通过注射给药；由于需求火爆，产能受到挑战。而且不少使用者被其副作用所困扰，包括恶心、呕吐、腹泻和腹痛等胃肠道副作用，对肌肉损失的担忧，以及停药反弹。因此，诺和诺德和礼来两家制药巨头还在开发更便捷、更高效且安全的新一代减肥药。礼来推出了GLP-1R/GIPR/GCGR三靶点激动剂Retatrutide和口服小分子GLP-1R激动剂Orforglipron。 Retatrutide 该药为GLP-1R/GIPR/GCGR三靶点激动剂，是替尔泊肽的潜在迭代产品，给药频率为每周一次。礼来预期最高剂量可以减重22-24%，主要是脂肪的减少，预计降糖效果可以将Hb1Ac降低2%。目前，礼来围绕Retatrutide已经注册了9项三期临床试验：3项2型糖尿病、6项减重试验，包括一项Retatrutide头对头替尔泊肽用于减重研究。该研究计划入组800例肥胖患者，预计2027年4月完成。 Orforglipron 该药是一种新型的口服小分子GLP-1R激动剂，给药频率为每日一次。目前，该药处于临床Ⅲ期阶段，适应症包括肥胖、2型糖尿病、心血管疾病等。 Orforglipron的Ⅱ期临床数据显示，治疗36周，45mg剂量组减重14.7%，相较安慰剂组减重12.4%。 Orforglipron减重临床数据图片来源：参考资料1 对比口服Semaglutide 50mg组临床Ⅲ期OASIS 1试验36周减重约14%，orforglipron减重效果似乎更胜一筹。作为GLP-1R小分子赛道的领头羊，orforglipron的表现，让人们对其Ⅲ期临床数据充满了期待。诺和诺德则推出了司美格鲁肽与胰淀素类似物cagrilintide的药物组合CagriSema，以及口服药物monlunabant、amycretin。图片来源：诺和诺德 CagriSema CagriSema是司美格鲁肽与胰淀素类似物cagrilintide的固定剂量药物组合，给药频率为每周一次皮下注射。 2022年，诺和诺德开始了CagriSema肥胖症的Ⅲ期临床系列研究REDEFINE，包括一项CagriSema与替尔泊肽头对头对照用于减肥的Ⅲ期临床试验（REDEFINE 4）。该研究计划入组800例肥胖或超重患者，接受2.4mg Cagrilintide+2.4mg司美格鲁肽或替尔泊肽高剂量15mg治疗，预计于2025年8月完成。图片来源：诺和诺德 Monlunabant Monlunabant（曾用名INV-202）是一种小分子口服大麻素受体1（CB1）反向激动剂。诺和诺德于2023年8月以超10亿美元收购加拿大公司Inversago pharma囊获了这一疗法。其2a期临床试验结果显示，从基线体重110.1公斤开始，经过16周治疗，每日一次服用10 mg剂量monlunabant的参与者平均体重减少了7.1公斤，而安慰剂组仅减少了0.7公斤。然而，monlunabant高剂量组看到的减重效果提升有限。 Amycretin 该药是一款GLP-1受体和胰淀素受体的长效共激动剂，诺和诺德开发了口服和皮下注射两种剂型，其中口服剂型在临床进展上更快，给药频率为每日一次。在减重方面，接受治疗12周后，Amycretin组患者体重下降幅度达13.1%，相较之下，安慰剂组患者的体重下降幅度仅为1.1%。 02 结语在崛起的减重、代谢领域，国产创新药也占据了重要地位。 2023年11月，中国biotech公司诚益生物与阿斯利康就小分子GLP-1R激动剂ECC-5004达成一项超20亿美元的独家许可协议。 2024年5月，中国制药巨头江苏恒瑞医药将其GLP-1R药物组合的中国以外权利授权给新成立的美国生物技术公司Hercules，交易总金额超过60亿美元，且由此开辟的newco模式正在成为创新药出海的新潮流。随着国产GLP-1R药物的研发推进，有望在这一新领域实现突破性的进展，分得一杯羹。声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 小月石转载开白 | 马老师 18996384680（同微信）商务合作 | 王存星 19922864877（同微信）阅读原文，是受欢迎的文章哦

财报临床3期

2024-11-06

·echemi

Novo Nordisk's New Weight Loss Drug Achieves 25% Weight Reduction, Shocking the Market!

In order to maintain its leading position in the weight loss drug market, Novo Nordisk is currently actively developing a new GLP-1 drug called CagriSema, according to the latest media reports. It is reported that the new drug is expected to achieve at least 25% weight loss, compared to the previous generation of weight loss drug Wegovy, CagriSema will be significantly more effective in weight loss, without additional side effects. Novo Nordisk said CagriSema will effectively address the problem of patients regaining weight after discontinuing the drug and is expected to be the most effective weight loss drug on the market to date. In addition, the efficacy of the drug against type 2 diabetes is still being further explored and studied. Novo Nord's planned CagriSema combines two intestinal hormones: a long-acting GLP-1 receptor agonist, Smaglutide, and a long-acting Amylin analogue, Cagrilintide. The combination of these two ingredients is expected to lead to more significant weight loss for patients, while reducing the occurrence of side effects. Matthias Tschop, CEO of the Helmholtz Institute in Munich and one of the scientists behind the multi-receptor therapy foundation, says that patients taking this double-acting drug are often able to lose more weight without suffering more side effects than those taking GLP-1 alone. That view is echoed by Henrik Sillesen, chief medical officer at health analytics firm Airfinity Ltd. Henrik Sillesen noted that after GLP-1, GIP and glucagon, amylin has become the next important target that is actively being explored in the field of weight loss. Adam Steensberg, chief executive of Zealand, also said that taking amylin is gentler than GLP-1 drugs, and that GLP-1 drugs may reduce appetite, while amylin will help patients stay full for longer. This view further highlights the potential advantages of CagriSema in the weight loss drug market.

100 项与 CagriSema 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床3期	保加利亚	Novo Nordisk Pharmaceuticals Pty Ltd.	2023-09-27
2型糖尿病	临床3期	哥伦比亚	Novo Nordisk Pharmaceuticals Pty Ltd.	2023-09-27
2型糖尿病	临床3期	克罗地亚	Novo Nordisk Pharmaceuticals Pty Ltd.	2023-09-27
2型糖尿病	临床3期	捷克	Novo Nordisk Pharmaceuticals Pty Ltd.	2023-09-27
2型糖尿病	临床3期	丹麦	Novo Nordisk Pharmaceuticals Pty Ltd.	2023-09-27
2型糖尿病	临床3期	芬兰	Novo Nordisk Pharmaceuticals Pty Ltd.	2023-09-27
2型糖尿病	临床3期	墨西哥	Novo Nordisk Pharmaceuticals Pty Ltd.	2023-09-27
2型糖尿病	临床3期	斯洛文尼亚	Novo Nordisk Pharmaceuticals Pty Ltd.	2023-09-27
2型糖尿病	临床3期	韩国	Novo Nordisk Pharmaceuticals Pty Ltd.	2023-09-27
2型糖尿病	临床3期	瑞典	Novo Nordisk Pharmaceuticals Pty Ltd.	2023-09-27

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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


EASD2023	N/A	-	-	CagriSema	廠願襯糧觸繭鹽蓋窪鑰(鹽鹽壓願獵蓋憲築衊壓) = 觸餘憲鬱鹹網鹽襯淵餘築積蓋壓窪鬱艱艱選繭 (鏇顧鬱艱餘獵夢廠範憲 ) 更多	积极	2023-10-03
				Cagrisema	廠願襯糧觸繭鹽蓋窪鑰(鹽鹽壓願獵蓋憲築衊壓) = 鏇壓餘鏇憲膚餘醖鹽選築積蓋壓窪鬱艱艱選繭 (鏇顧鬱艱餘獵夢廠範憲 )
NAASO2022	N/A	-	-	Vehicle control	壓網簾顧廠選鏇鑰簾築(襯衊製廠襯簾繭製願鹽) = 窪構簾鹽餘築淵鏇積積艱製艱窪顧齋窪齋構觸 (淵遞製範獵蓋壓簾鑰築 ) 更多	-	2022-11-21
				CagriSema	壓網簾顧廠選鏇鑰簾築(襯衊製廠襯簾繭製願鹽) = 鑰選壓壓鑰憲顧憲淵鬱艱製艱窪顧齋窪齋構觸 (淵遞製範獵蓋壓簾鑰築 ) 更多