A PHASE 1, OPEN LABEL, 2-PERIOD, FIXED SEQUENCE, STUDY TO ASSESS THE MASS BALANCE, ABSOLUTE BIOAVAILABILITY OF 14C PF 06826647 IN HEALTHY MALE PARTICIPANTS

The purpose of the study is to determine the metabolism and excretion following a single oral administration of 14C-PF-06826647-LR (14C labelled PF-06826647 with lower radioactivity per mass unit) in fed conditions. This information will enable assessment of clearance mechanisms of PF-06826647 as well as identify metabolites. In addition, this study will determine absolute bioavailability of PF-06826647 and understand intravenous (IV) pharmacokinetic (PK).

开始日期2020-11-10

申办/合作机构

Pfizer Inc.

NL-OMON50100

/ CompletedN/A

A phase 1, open label, 2-period, fixed sequence, study to assess the mass balance, absolute bioavailability of 14C-PF-06826647 in healthy male participants - Mass balance and absolute bioavailability of 14C-PF-06826647 in men.

开始日期2020-11-10

申办/合作机构

Pfizer Inc.

NCT04209556

/ Withdrawn临床2期

A PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PARALLEL-GROUP, PLACEBO-CONTROLLED STUDY WITH AN OPEN LABEL EXTENSION TO EVALUATE THE SAFETY AND EFFICACY OF PF-06826647 IN PARTICIPANTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS

The purpose of this study is to evaluate efficacy and safety of PF-06826647 in moderate to severe ulcerative colitis

开始日期2020-09-30

申办/合作机构

Pfizer Inc.

100 项与 Ropsacitinib 相关的临床结果

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100 项与 Ropsacitinib 相关的转化医学

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100 项与 Ropsacitinib 相关的专利（医药）

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项与 Ropsacitinib 相关的文献（医药）

2025-09-01·JAMA Dermatology

Efficacy and Safety of Medical Interventions for Moderate to Severe Hidradenitis Suppurativa

Review

作者: Midgette, Bria ; Cohn, Erica ; Strunk, Andrew ; Garg, Amit ; Frasier, Kelly

Importance:

There is limited comparative information on regulatory approved and pipeline treatments in hidradenitis suppurativa (HS).

Objective:

To compare efficacy, safety, and tolerability of treatments for moderate to severe HS.

Data Sources:

MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from inception to June 28, 2024.

Study Selection:

Phase 2 and 3 randomized clinical trials of medical interventions (cytokine inhibitors, small molecule inhibitors, cell inhibitors, and other novel immune or inflammatory modifiers) for adults with moderate to severe HS having primary efficacy assessments between 12 and 16 weeks.

Data Extraction and Synthesis:

Data extraction and risk of bias assessments were performed independently by 2 reviewers. Efficacy outcomes were analyzed using random-effects network meta-analysis. Safety and tolerability outcomes were analyzed using pairwise fixed-effect meta-analyses vs placebo. Data analysis was performed between August 22, 2024, and April 7, 2025.

Main Outcomes and Measures:

Primary efficacy, safety, and tolerability outcomes were Hidradenitis Suppurativa Clinical Response (HiSCR)-50, occurrence of serious adverse events (SAEs), and treatment discontinuation due to adverse events, respectively. HiSCR-75 was a secondary efficacy outcome.

Results:

Of 26 eligible trials, 25 had available HiSCR-50 data, including 5767 total patients and 39 unique treatments. Compared with placebo, the following treatments were associated with significantly higher HiSCR-50 response rates: sonelokimab, 120 mg, every 4 weeks; lutikizumab, 300 mg, every 2 weeks; adalimumab, 40 mg, once per week; sonelokimab, 240 mg, every 2 weeks; bimekizumab, 320 mg, every 2 weeks; povorcitinib, 15 mg, once per day; bimekizumab, 320 mg, every 4 weeks; secukinumab, 300 mg, every 4 weeks; and secukinumab, 300 mg, every 2 weeks. Most differences between adalimumab, 40 mg, once per week, and other targeted treatments were not statistically significant. The percentage of patients experiencing SAEs ranged from 0% to 10% in the placebo groups, 0% to 8% in the adalimumab (40 mg, once per week) groups, and 0% to 6% in the other active treatment groups. The percentage of patients discontinuing treatment due to adverse events ranged from 0% to 10% in the placebo groups, 0% to 4% in the adalimumab (40 mg, once per week) groups, and 0% to 15% (ropsacitinib) in the other active treatment groups.

Conclusions and Relevance:

This network meta-analysis provides evidence for the comparative efficacy and safety of currently approved and pipeline medications for moderate to severe HS in the absence of head-to-head trials.

2025-03-28·Recent Advances in Inflammation & Allergy Drug Discovery

Pharmacological Management of Psoriasis: Current Landscape and Future Perspectives

Article

作者: Tomar, Anush ; Bawari, Sweta ; Pedwar, Roopal

Abstract::

Psoriasis is a relapsing, chronic, and inflammatory disease of the skin. However, its impact goes beyond just pathophysiology and takes a toll on the physical and psychological aspects of the health of the afflicted, lowering the quality of life significantly. It is also a mechanistically complex disease with a substantial immune component. Therefore, ongoing treatment strategies focus on targeting at least one immune component associated with the disease development and progression by employing biological agents like IL-1 inhibitors, IL-23 inhibitors, IL-36 inhibitors, and TNF-α inhibitors. Psoriasis-induced disruptions in cellular signalling pathways have drawn significant attention as novel drug targets. Numerous novel synthetic agents, such as JAK/STAT inhibitors [ruxolitinib, peficitinib], TYK2 inhibitors [zasocitinib, ropsacitinib], RORꝩT inhibitors [cedirogant], A3AR agonists [piclodenoson], and CXCR2 antagonists [vimnerixin] are undergoing extensive clinical trials and have demonstrated beneficial outcomes in multiple phases of these trials. Deucravacitinib, an orally administered TYK2 inhibitor, has recently received FDA approval for the treatment of moderate to severe plaque psoriasis. These synthetic agents hold promise to change the outlook of psoriasis management by modulating specific molecular targets associated with the dysregulated immune response observed in psoriasis. Moreover, these pathways can be exploited to personalize anti-psoriatic therapy, minimize side effects, and maximize therapeutic outcomes. Altogether, the integration of biological agents and synthetic agents can overcome the challenges associated with the management of the repertoire of psoriatic pathophysiology and symptoms.

2025-02-01·AUSTRALASIAN JOURNAL OF DERMATOLOGY

A systematic review of the efficacy of TYK2 inhibitors in patients with dermatological disease

Review

作者: Haggett, Malindi Georgia ; Lee, Sangho ; Lai, Francis Yi Xing

Abstract:

This study systematically reviews existing data on the efficacy of Tyrosine Kinase 2 (TYK2) inhibitors in comparison to placebo or standard treatments for therapeutic benefit and improving quality of life in dermatological diseases. Seventeen records representing 13 clinical trials, one matching‐adjusted indirect comparison, and one case study were included. Results indicate that Deucravacitinib is superior to placebo, Apremilast and Adalimumab in treating adult patients with moderate‐to‐severe plaque psoriasis and superior to placebo in the treatment of adults with systemic lupus erythematosus. Comparative investigations on Brepocitinib and Ropsacitinib were more limited. Oral Brepocitinib demonstrated superiority over placebo in managing alopecia areata, and hidradenitis suppurativa. Topical Brepocitinib exhibited superiority over placebo in treating atopic dermatitis, but not plaque psoriasis. Ropsacitinib demonstrated superiority over placebo in the management of plaque psoriasis. Brepocitinib and Ropsacitinib had more side effects than Deucravacitinib.

项与 Ropsacitinib 相关的新闻（医药）

2025-09-17

·新药猎人笔记

TYK2/JAK1抑制剂在皮肌炎三期临床试验中结果积极，2026年NDA

2025年9月17日，Roivant和Priovant Therapeutics宣布了brepocitinib在皮肌炎（DM）三期VALOR试验中的积极结果。这是一项为期52周的安慰剂对照试验，brepocitinib 30 mg每日一次口服给药，在主要终点和所有九个关键次要终点上均显示出与安慰剂相比具有临床意义和统计学显著性的改善。受此消息影响，公司股价上涨7.7%！试验结果在主要终点上，brepocitinib 30 mg在第52周的平均总改善分数（TIS）为46.5，而安慰剂组为31.2，p值为0.0006。在所有时间点，包括早在第4周，brepocitinib 30 mg与安慰剂相比在平均TIS上均显示出统计学显著差异。此外，超过三分之二的brepocitinib 30 mg患者至少有中等程度的反应（TIS≥40），近一半的患者有重大反应（TIS≥60）。在进入试验时有中度至重度皮肤疾病的患者中，brepocitinib 30 mg组有44%在第52周实现了皮肤临床缓解，而安慰剂组为21%。此外，试验中还观察到brepocitinib在减少患者对糖皮质激素依赖方面的优势。大约75%的患者在进入VALOR试验时正在使用背景糖皮质激素，brepocitinib 30 mg组中有62%的患者在研究结束时糖皮质激素剂量降至≤2.5 mg/天（安慰剂组为34%），42%的患者能够完全停用糖皮质激素（安慰剂组为23%）。安全性：brepocitinib 30 mg的安全性与以往的临床试验一致。特别关注的不良事件（AESIs），包括恶性肿瘤、心血管事件和血栓栓塞事件，在brepocitinib 30 mg组的发生频率并不高于安慰剂组。 Priovant计划在2026年上半年向美国食品药品监督管理局（FDA）提交brepocitinib用于治疗皮肌炎的新药申请（NDA）。如果获得批准，brepocitinib有望成为首个针对皮肌炎的靶向疗法，为患者提供一种新的治疗选择。 2022年，辉瑞和Roivant Sciences共同成立抗炎药物NewCo公司Priovant Therapeutics，以开发原属辉瑞的自身免疫疾病药物brepocitinib和ropsacitinib。辉瑞持有Priovant的25%股权。结束语：皮肌炎是一种罕见的自身免疫性疾病，主要影响皮肤和肌肉，导致肌肉无力、皮肤红斑和皮疹等症状，严重影响患者的生活质量。目前，皮肌炎的治疗选择有限，且通常需要长期使用糖皮质激素，这可能会带来一系列副作用。brepocitinib的三期临床试结果为患者带来了新的希望。高光制药的JAK1/TYK2抑制剂TLL-018，在2023年EULAR上报告了与托法替布在活动性类风湿关节炎病人中头对头比较的II期临床中期分析结果。

临床3期临床2期临床成功

2025-04-11

·抗体圈

口服自免药物革新：TYK2 抑制剂如何重塑治疗格局？

银屑病作为一种慢性系统性免疫疾病，影响全球约1.25亿人，治疗需求庞大但长期依赖生物制剂（如IL-17/IL-23抗体）。尽管生物制剂疗效显著，但是生物制剂注射依赖性和免疫原性限制了患者依从性。口服小分子药物因其便利性和潜在成本优势成为新趋势。银屑病口服药物领域长期依赖PDE4抑制剂阿普米司特，但该药物疗效显著低于生物制剂且存在胃肠道副作用，市场渗透未达预期。随着对疾病机制的深入理解，靶向TYK2的口服抑制剂成为新一代研发热点，正在重塑银屑病治疗格局。TYK2 属于JAK家族成员，通过结合其JH2变构域实现高选择性抑制，区别于传统JAK抑制剂对JH1激酶域的非特异性作用。这种变构抑制机制避免了对JAK1/2/3的干扰，显著降低感染、血栓等副作用风险。以全球首个TYK2变构抑制剂如氘可来昔替尼（Deucravacitinib）为例，其全球3期临床POETYK PSO-LTE研究最新5年结果显示，持续接受氘可来昔替尼治疗至第256周时，PASI 75和PASI 90应答率分别为81.8%和55.3%。这个研究结果证实了氘可来昔替尼在银屑病治疗领域疗效持久性与安全性的双维度突破。1水火交织下，中国药企崛起在全球 TYK2 抑制剂的研发版图上，一场冰火交织的较量正在上演。BMS的氘可来昔替尼（Deucravacitinib）是全球首个获批的TYK2变构抑制剂，2022年在美国获批后迅速在多个国家上市，并于2023年快速纳入中国医保，却因IL-17抗体等生物制剂的强势竞争，2024年全球销售额仅2.46亿美元，远低于40亿美元的峰值预期。辉瑞的竞争性抑制剂Ropsacitinib虽在银屑病2期临床中展现PASI 75应答率61%的优势，却因无法规避JAK通路脱靶风险，最终被迫退出该适应症赛道。Ventyx的高选择性变构抑制剂VRTX958更因2期银屑病临床疗效不足，连带克罗恩病适应症研发折戟，为靶点研发蒙上阴影。尽管如此，TYK2作为银屑病口服赛道的重要靶点，全球药企对其探索从未停歇。纵观TYK2研发管线全局，仍有30多款相关药物已挺进临床阶段。中国药企的崛起尤为显著，全球近50%的TYK2抑制剂管线来自中国，益方生物、诺诚健华等通过变构抑制机制实现差异化竞争。临床后期管线中，武田的 TAK-279值得关注。该药物是武田在2022年斥资 60 亿美元收购而获得的一款TYK2变构抑制剂。其2b 期临床数据显示，30mg剂量TAK-279治疗中重度斑块状银屑病患者12周PASI 75 比例为67%，目前已启动3 期研究。武田预判其在银屑病及银屑病关节炎领域的峰值销售额可达 30-60 亿美元。诺诚健华拥有两款 TYK2 抑制剂，包括 ICP-3322（JH1 抑制剂）和 ICP -488（JH2 抑制剂），两款产品目前均处于临床3期，属于全球研进度靠前位置。ICP-488作为变构抑制剂，在治疗12周的临床2期研究中，其6mg/9mg 剂量下PASI 75应答率达77.3%/78.6%。诺诚健华双管线齐头并进，形成适应症拓展的协同效应。翰森制药的HS-10374是一款TYK2选择性变构抑制剂，目前处于治疗中重度斑块状银屑病的临床3期研究阶段。临床2期研究结果显示，HS-10374 6mg和12mg 剂量下治疗12周PASI75 分别为 28.6% 和 72.1%, 显著高于安慰剂组的 7.5%。益方生物的D-2570是一款高选择性的TYK2 JH2抑制剂，根据益方生物披露，D-2570与BMS 的Deucravacitinib相比对JAK1的选择性更好。目前已完成治疗银屑病的2期临床试验，并取得了积极的临床试验结果。具体数据是，治疗12周时，低、中、高三个剂量组中PASI 75应答率为85.0%-90.0%，显著高于安慰剂组的12.5%。对比其他中重度银屑病治疗药物临床数据，D-2570以85%-90% 的PASI 75应答率胜过（非头对头研究）TAK-279等竞品，且初步来看数据已经可以媲美古塞奇尤单抗等生物制剂，显示出BIC的潜力。在全球TYK2抑制剂的研发进程里，中国药企表现亮眼，展现出强大的竞争力。从数量上看，占比已然超过50%，研究进度也毫不逊色。除临床后期管线外，中国药企在不同研发阶段均形成梯队优势。启元生物颇具实力，它有两款在研产品，均为TYK2/JAK1双靶点抑制剂，适应症覆盖银屑病、特应性皮炎等多个自免领域。其中，QY-201已稳步推进至临床 3期，QY-211处于临床2期。正大天晴的TQH-3906同样处于临床2期，聚焦克罗恩病等胃肠自免疾病，与银屑病管线形成差异化竞争。康哲药业的 CMS-D001顺利迈入临床1期。2在百亿市场中寻找最优解银屑病治疗领域正经历着前所未有的变革。根据Global Market数据，2032年全球银屑病市场规模预计将攀升至605亿美元，2023-2032年复合年增长率达8.6%。这一增长轨迹不仅源于疾病患病人群的扩大，更与创新药物的迭代升级密切相关。中国银屑病患者数量已超过800万，且随着公众对疾病认知的提升和诊疗需求的释放，本土市场展现出更为迅猛的增长动能。沙利文报告显示，2022年中国银屑病药物市场规模为14.36亿美元，2025年预计增至32.55亿美元（CAGR 31.4%），2030年将进一步突破至99.44亿美元，成为全球最具潜力的增量市场之一。在这场千亿市场的角逐中，TYK2抑制剂作为新兴靶点药物备受瞩目。相较于 JAK抑制剂的泛靶点抑制，TYK2抑制剂展现出更高的选择性，理论上可降低脱靶效应带来的副作用风险。然而，临床应用中仍需警惕长期免疫抑制引发的感染风险。尽管现有数据显示其安全性优于第一代 JAK 药物，但随着用药人群的扩大，感染相关不良事件的监测仍需持续强化。TYK2抑制剂的商业化进程面临着来自同类靶点及替代机制药物的双重竞争。首先，IL-17通路抑制剂作为银屑病治疗的成熟靶点，其核心机制在于精准阻断 IL-17A 介导的炎症级联反应。这一机制的靶向干预在临床中展现出显著疗效，司库奇尤单抗（Cosentyx）和依奇珠单抗（Taltz）为代表的IL-17A抑制剂，凭借高应答率和长期安全性数据，占据全球银屑病生物药市场的半壁江山。2024年，司库奇尤单抗全球销售额同比增长25%至61.41亿美元，成为诺华第二大畅销药。依奇珠单抗则以全年销售额超30亿美元的表现，稳居自免领域重磅药物行列。IL-17这类药物适应症覆盖广泛（包括银屑病、关节炎、脊柱炎等），市场潜力不容小觑。强生研发的口服IL-23R拮抗剂是TYK2抑制剂的另一个劲敌。Icotrokinra在3期ICONIC-LEAD研究中表现亮眼：治疗16周时，PASI 90应答率达49.6%，IGA 0/1比例高达64.7%，非头对头比较中优于部分已上市口服竞品。面对激烈的竞争环境，TYK2 抑制剂正通过“适应症外延”与“技术迭代”打开新的增长空间。在疾病领域拓展上，该类药物已从单一的银屑病治疗，向更广泛的自身免疫性疾病领域渗透。BMS 的 Deucravacitinib作为首个获批的 TYK2 变构抑制剂，目前正开展银屑病关节炎、克罗恩病的 3 期临床研究，同时探索干燥综合征、系统性红斑狼疮等复杂适应症的潜力。武田的 TAK-279除银屑病关节炎外，已启动克罗恩病、溃疡性结肠炎的全球多中心试验。这类疾病目前存在巨大未满足需求，现有生物制剂（如抗 TNF 药物）存在注射不便、耐药性等问题，口服 TYK2 抑制剂有望成为更优解。中国药企亦加速布局，正大天晴的TYK2抑制剂TQ-05820在银屑病2期研究中展现良好疗效，同步开展克罗恩病的探索。Sudo Biosciences另辟蹊径，开发脑穿透性TYK2抑制剂，针对阿尔茨海默病、多发性硬化症等神经系统疾病，试图开辟“神经 - 免疫”跨界治疗的新赛道。一旦这些新适应症研发成功，TYK2抑制剂的适用人群将大幅拓宽，形成“一药多治”的格局；同时，其市场潜力也会随之增长。技术创新层面，双靶点抑制剂成为研发热点。TYK2/JAK1 双通路理论上既能增强药物疗效，又可在一定程度上减少单一靶点高剂量带来的毒性风险。启元生物、高光制药等企业的候选药物正在临床研究中。结语TYK2 抑制剂通过高选择性机制革新了银屑病口服治疗格局，其疗效与安全性优势显著。全球研发竞争激烈，而中国药企凭借临床数据优势和国际化布局，成为全球竞争的关键变量。未来，通过适应症拓展、技术迭代等策略，TYK2 抑制剂有望成为银屑病及其他自免疾病的一线治疗选择，同时推动中国创新药国际化进程。识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

临床2期临床3期免疫疗法临床结果并购

2023-11-27

·FierceBiotech

Roivant ends longshot lupus program after phase 2 fail

Priovant, which is keeping the specific data to itself for now, had hoped the phase 2 study would set it up to seek approval for brepocitinib in lupus. Roivant’s CEO Matt Gline always knew the lupus drug brepocitinib was a longshot: “Anybody who is not afraid of a lupus study is an idiot, you shouldn’t trust them,” he told Fierce Biotech at the beginning of the year. Now, it seems Gline’s fear was warranted. The therapy, snagged from Pfizer in 2022, did not lead to improvement in lupus disease activity at week 52, failing the main goal of a phase 2 study. Roivant’s Priovant unit will now drop the indication but continue with brepocitinib in a handful of other conditions including non-infectious uveitis (NIU). Gline blamed the failure on high placebo response in the trial, according to a statement. Brepocitinib was tested in adult patients with moderate to severe active systemic lupus erythematosus. Efficacy was measured using a common scale for lupus called the Systemic Lupus Erythematosus Responder Index change of 4 (SRI-4). “We saw some of the highest SRI-4 responder rates ever observed in a lupus study in the active arm of this trial, along with a favorable safety and tolerability profile,” Gline said in the Monday release. “Unfortunately, we also saw the highest placebo response rate observed in any significant SLE study, and as such it was not possible to truly assess the impact of the drug, or to establish sufficient differentiation from other therapies in lupus patients.” Roivant formed the company Priovant around brepocitinib and another TYK2 inhibitor called PF-06826647, or ropsacitinib, last year in a deal with Pfizer. The Big Pharma holds a 25% stake in Priovant. Priovant, which is keeping the specific data to itself for now, had hoped the phase 2 study would provide the data needed to seek an approval in lupus for brepocitinib. Now, the company will turn to the rest of the brepocitinib program. The TYK2 inhibitor is being tested in a phase 2 trial for NIU with a readout expected in the first quarter of 2024. A phase 3 readout in dermatomyositis is expected sometime in 2025. Roivant said that brepocitinib has also demonstrated potential benefit in six placebo-controlled mid-phase studies in psoriasis, psoriatic arthritis, alopecia areata, hidradenitis suppurativa, ulcerative colitis and Crohn’s disease. Gline said today’s results show that brepocitinib “is a highly active agent with a good safety profile.” Roivant is just the latest company to be stymied by lupus. Horizon Therapeutics, which was bought out by Amgen in October, suffered a phase 2 failure in July as well. Amgen also cut two of its own programs earlier this year, as did Eli Lilly.

临床2期并购临床3期临床失败临床结果

100 项与 Ropsacitinib 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
溃疡性结肠炎	临床2期	美国	Pfizer Inc.	2020-09-30
化脓性汗腺炎	临床2期	美国	Pfizer Inc.	2019-12-02
化脓性汗腺炎	临床2期	澳大利亚	Pfizer Inc.	2019-12-02
化脓性汗腺炎	临床2期	加拿大	Pfizer Inc.	2019-12-02
斑块状银屑病	临床2期	美国	Pfizer Inc.	2019-06-27
斑块状银屑病	临床2期	日本	Pfizer Inc.	2019-06-27
斑块状银屑病	临床2期	加拿大	Pfizer Inc.	2019-06-27
斑块状银屑病	临床2期	波兰	Pfizer Inc.	2019-06-27

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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


NCT04092452 (Pubmed \| NEJM Evid) 人工标引	临床2期	化脓性汗腺炎 JAK1 \| TYK2	194	zimlovisertib	觸範觸鏇憲製鏇鬱艱獵(簾簾遞鬱蓋鏇築鹽選廠) = 製糧築築蓋觸構鹽網繭網範鑰衊壓餘範襯窪獵 (積糧選蓋築構糧築鏇蓋 ) 更多	积极	2024-02-27
NCT04092452 (CTgov)	临床2期	化脓性汗腺炎	194	placebo+PF-06826647+PF-06700841+PF-06650833 (Placebo)	憲醖鏇繭憲鹽鹽壓願構 = 簾糧簾襯醖鑰範艱夢繭選觸壓構鹽襯顧蓋淵築 (憲範襯憲積膚簾壓壓鬱, 襯衊繭範觸廠選襯衊窪 ~ 衊積觸構繭構襯獵襯顧) 更多	-	2023-06-15
NCT04092452 (CTgov)	临床2期	化脓性汗腺炎	194	PF-06650833 (PF-06650833 400mg QD)	憲醖鏇繭憲鹽鹽壓願構 = 襯壓選艱衊憲膚艱餘鹹選觸壓構鹽襯顧蓋淵築 (憲範襯憲積膚簾壓壓鬱, 獵襯窪鬱鬱範製壓鑰窪 ~ 齋醖築壓願獵簾願網餘) 更多	-	2023-06-15