A pivotal, randomized, double-blind, placebo-controlled, multi-center therapeutic study for patients age 4 and older with a confirmed diagnosis of CACNA1A. The objective of this study is to evaluate the safety, tolerability and efficacy of N-acetyl-L-leucine (IB1001) compared to standard of care.

开始日期2026-08-17

申办/合作机构

IntraBio Ltd.

NCT06673056

/ Active, not recruiting临床3期

Effects of N-Acetyl-L-Leucine on Ataxia-Telangiectasia (A-T: A Phase III, Randomized, Placebo-controlled, Double-blind, Crossover Study

A pivotal, randomized, double-blind, placebo-controlled, multi-center therapeutic study for patients age 4 and older with a confirmed diagnosis of Ataxia-Telangiectasia (A-T). The objective of this study is to evaluate the safety, tolerability and efficacy of N-acetyl-L-leucine (IB1001) compared to standard of care.

开始日期2025-03-18

申办/合作机构

IntraBio Ltd.

NCT05163288

/ Recruiting临床3期

Effects of N-Acetyl-L-Leucine on Niemann-Pick Disease Type C (NPC): A Phase III, Randomized, Placebo-controlled, Double-blind, Crossover Study

A pivotal, randomized, double-blind, placebo controlled, multi-center therapeutic study for patients age 4 and older with a confirmed diagnosis of Niemann Pick disease type C (NPC). The objective of this study is to evaluate the safety, tolerability and efficacy of N-acetyl-L-leucine (IB1001) compared to standard of care.
Following this randomized, double-blind, placebo-controlled "Parent Study", an extension phase is conducted for (1) patients who completed the "Parent Study" and (2) patients who are enrolled directly into the Extension Phase. Currently, the Extension Phase provides patients with 3 years of open-label treatment.

开始日期2022-06-30

申办/合作机构

IntraBio Ltd.

100 项与 N-乙酰-L-亮氨酸相关的临床结果

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100 项与 N-乙酰-L-亮氨酸相关的转化医学

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100 项与 N-乙酰-L-亮氨酸相关的专利（医药）

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项与 N-乙酰-L-亮氨酸相关的文献（医药）

2026-07-03·JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS

Amino acid osmolytes disrupting intradomain interactions reduce the amyloidogenicity of α-synuclein: studies with charged l -amino acids and their derivatives

Article

作者: Prakash, Jogadhenu S. S. ; Prabhu, N. Prakash ; Saurabh, Archi ; Chauhan, Suraj

Aggregation of α-synuclein (α-syn) is a hallmark of Parkinson's and dementia with Lewy bodies pathogenesis. The high plasticity and lack of stable tertiary structure make α-syn more susceptible to its surrounding environment. Under stress conditions, small organic molecules known as osmolytes accumulate inside the cells. They affect the conformational states and fibrillation pathways of proteins. Here, the effects of eight different amino acid osmolytes (charged: l-glutamate, l-aspartate, l-lysine, l-arginine; amide side chains: l-glutamine, l-asparagine; and N-acetylated: N-acetyl-l-glutamic acid, N-acetyl-l-lysine) on the fibrillation of human α-synuclein were examined. Arginine and N-acetyl-l-lysine inhibited the fibrillation at concentrations above 0.2 and 0.4 M, respectively. Lysine, asparagine, and glutamate accelerated the fibrillation by reducing lag time. N-acetyl-l-glutamic acid induced lag-independent fibrillation, whereas glutamine and asparagine showed concentration-dependent effects on the fibrillation with reduced lag time at higher concentrations. Molecular dynamics simulations revealed that interdomain contacts facilitated the fibrillation. The amino acids interacting predominantly through van der Waals interactions reduced the lag time of α-syn. However, the amino acids having strong electrostatic interactions with the protein disrupted intradomain contacts, favored extended conformation, and inhibited the fibril formation.

2026-07-01·LANCET NEUROLOGY

Safety and efficacy of levacetylleucine in ataxia-telangiectasia: a phase 3, randomised, double-blind, placebo-controlled crossover trial

Article

作者: Skorvanek, Matej ; Foltan, Tomas ; Bremova-Ertl, Tatiana ; Thakur, Nivedita ; Del Mar Garcia Romero, Maria ; Bolton, Clare ; Gautschi, Matthias ; Schmahmann, Jeremey ; Hoche, Franziska ; Kolnikova, Miriam ; Hahn, Andreas ; Han, Vladimir ; Martakis, Kyriakos ; Prasad, Manish ; Perlman, Susan ; Thiel, Moritz ; Panagioti, Ouliana

BACKGROUND:

Ataxia-telangiectasia is a rare, autosomal recessive neurodegenerative disorder. Levacetylleucine (N-acetyl-L-leucine) has been shown to be efficacious for the treatment of neurological manifestations and to have a disease-modifying effect in lysosomal storage disorders such as Niemann-Pick disease type C. We aimed to assess the safety and efficacy of levacetylleucine for paediatric and adult patients with ataxia-telangiectasia.

METHODS:

In this phase 3, randomised, double-blind, placebo-controlled crossover trial, participants were enrolled across ten research hospitals in Germany, Slovakia, Spain, Switzerland, the UK, and the USA. Eligible patients aged 4 years or older with genetically confirmed ataxia-telangiectasia were randomly assigned (1:1) using interactive response technology to receive two or three times daily orally administered levacetylleucine or a matching placebo over two consecutive 12-week treatment periods (patients weighing 35 kg or more received 4 g per day of orally administered levacetylleucine or a matching placebo three times per day and patients weighing less than 35 kg received weight-tiered doses two or three times per day based on approximately 0·1 g/kg per day). All participants, investigators, and assessors were blinded to group assignment. The primary outcome was the mean change on the Scale for the Assessment and Rating of Ataxia (SARA), assessed at baseline and at the end of each 12-week treatment period of levacetylleucine or placebo. Safety and efficacy analyses were done in all randomly assigned patients who received at least one dose of study medication, and a linear mixed-effects model was used to account for data missing at random. The trial is registered with ClinicalTrials.gov, NCT06673056, and CTIS, 2024-517706-29; the open-label extension phase is ongoing.

FINDINGS:

Between March 18, 2025 and June 30, 2025, 77 participants with a genetically confirmed diagnosis of ataxia-telangiectasia were screened for inclusion. Four patients were excluded (not meeting inclusion criteria) and 73 were enrolled and randomly assigned (36 to levacetylleucine followed by placebo and 37 to placebo followed by levacetylleucine. 73 patients were included in the primary analysis and safety sets. 38 (52%) of 73 patients were female and 35 (48%) were male; 55 (75%) of 73 patients were White. 47 (64%) of 73 were younger than 18 years and 26 (36%) were aged 18 years or older. The mean change in the SARA total score with levacetylleucine was -1·92 (SD 2·81) versus -0·14 (2·38) with placebo (linear mixed model treatment effect -1·88 [SD 0·41], 95% CI -2·70 to -1·06; p<0·0001). 54 adverse events occurred in 29 patients receiving levacetylleucine versus 75 events in 25 patients receiving placebo. No treatment-related serious adverse events or deaths occurred.

INTERPRETATION:

Levacetylleucine showed a significant and clinically meaningful improvement in functioning and was safe and well-tolerated, providing a favourable benefit-risk profile for the treatment of ataxia-telangiectasia. An ongoing open-label extension phase of this trial will investigate potential long-term, neuroprotective and disease-modifying effects.

FUNDING:

IntraBio.

2026-05-14·ChemMedChem

Synthesis of N‐Acetyl‐D‐ and ‐L‐Leucine‐ ¹³ C ₆ Tool Compounds in Neurodegenerative Disease

Article

作者: Ribeiro, João Gabriel ; Crepin, Damien ; Pantoş, G. Dan ; Nafie, Jordan ; McGown, Andrew ; Churchill, Grant ; Spencer, John ; Shepherd, Dawn ; Sharma, Manvendra ; Braine, Rebecca ; Platt, Frances M.

N‐acetyl‐L‐leucine (levacetylleucine, ALL) is the neuroprotective enantiomer of the racemic antivertigo drug, Tanganil (acetyl‐DL‐leucine, ADLL). ALL has recently been clinically repurposed for the treatment of Niemann Pick disease type C1, a disorder characterised by lysosomal accumulation of glycolipids and cholesterol. Isotopically labelled ALL was required, as well as its negative control, D‐enantiomer (ADL), to monitor the in vivo metabolic fate of the drug and to distinguish it from endogenous leucine and associated metabolites. Here, we describe the synthesis of N‐acetyl‐D‐ and ‐L‐leucine‐ 13 C 6 , as well as N‐acetyl‐L‐leucine‐ 13 C 1 , by N‐acetylation of their amino acid precursors, their spectroscopic characterisation and stereochemical and stability studies. These investigations found that formation of the products, as well as their water‐soluble sodium salt formulation, occurs without compromising stereochemical integrity.

项与 N-乙酰-L-亮氨酸相关的新闻（医药）

2026-08-25

·allsci.com

EMA rejects arimoclomol for Niemann-Pick disease type C over efficacy concerns

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) issued a negative opinion on July 23, 2026, recommending refusal of the Marketing Authorization Application (MAA) for arimoclomol (Meplyffa) submitted by Zevra Therapeutics (Nasdaq: ZVRA) for the treatment of Niemann-Pick disease type C (NPC) in patients aged two years and older in combination with miglustat. The Boston-based company has since requested a formal re-examination of the opinion. Zevra Therapeutics The CHMP's rationale, published in the EMA's assessment report, centered on insufficient demonstration of efficacy. The agency concluded that uncertainties in data handling and analytical approach undermined the reliability of the pivotal trial results. Specifically, the committee found no benefit in ambulation or cognition domains, and while a subgroup of patients also receiving miglustat showed a treatment effect favoring arimoclomol, the CHMP did not consider this finding robust given the absence of a demonstrated effect in the overall study population. The pivotal trial enrolled 50 children and adolescents aged 2 to 18 years. Arimoclomol received US FDA approval in September 2024 as the first approved treatment for NPC in the United States, indicated in combination with miglustat for neurological manifestations of the disease in patients aged two years and older. In Europe, treatment options for NPC neurological manifestations include miglustat (Zavesca) and Aqneursa (levacetylleucine), which received EU marketing authorization in January 2026 for patients aged six years and older weighing at least 20 kg. Aqneursa is indicated in combination with miglustat or as monotherapy when miglustat is not tolerated. The negative CHMP opinion leaves arimoclomol without EU marketing authorization, although compassionate-use access continues in countries where national authorities have authorized such programs. The NPC treatment landscape is becoming more active. Thousand Oaks, California-based Beren Therapeutics P.B.C. has an NDA for adrabetadex under FDA Priority Review for infantile-onset NPC, with a PDUFA target action date of November 17, 2026. Adrabetadex targets the underlying cholesterol trafficking defect via a distinct cyclodextrin-based mechanism and carries an infantile-onset-specific indication, positioning it as complementary rather than directly competitive with arimoclomol in the near term. A previous MAA for arimoclomol under the name Miplyffa was withdrawn in March 2022, making this the second attempt to secure European authorization for the molecule. The re-examination request does not guarantee a reversal of the CHMP opinion; if the committee upholds its position, the European Commission would be expected to issue a formal refusal decision. Access the AllSci platform to explore the science behind the news. Spot something wrong? Report an issue with this article

上市批准优先审批申请上市加速审批

2026-08-22

·微信

全球药品注册与前沿发展动态｜8月21日

全球药品注册与研发日报 Global Pharmaceutical Registration & R&D Daily Report 2026年8月21日（周五）信息覆盖时段：2026年8月20日 09:00 — 8月21日 09:00（过去24小时）一、本期核心事件／头条新闻【事件1｜恒瑞医药1类新药富马酸立康可泮胶囊获批上市，同日三款创新药获批临床】 8月20日，恒瑞医药公告其自主研发的1类新药富马酸立康可泮（HRS-5965）胶囊获国家药监局批准上市，用于治疗既往未接受过补体抑制剂治疗的阵发性睡眠性血红蛋白尿症（PNH）成人患者。该药为补体因子B抑制剂，从机制层面同时抑制血管内和血管外溶血，属罕见病领域重要创新突破，累计研发投入约2.78亿元（EvaluatePharma数据显示同靶点药物Fabhalta 2025年全球销售额约5.05亿美元）。同日，旗下三款创新药SHR-8203注射液（晚期实体瘤，国内外无同类药上市）、SHR-7012注射液（皮肤型红斑狼疮CLE）、HRS-3095片分别获药物临床试验批准，研发管线密集推进。【事件2｜FDA批准再生元Pasatru治疗超罕见骨病FOP】 FDA于8月19日正式批准再生元（Regeneron）Pasatru（garetosmab）用于成人进行性骨化性纤维发育不良（FOP，俗称“石头人症”）——全球约900名患者、多在30岁时需依赖轮椅的超罕见遗传病。该药是首个在安慰剂对照试验中显示可减少新发异位骨化（HO）病灶及疾病发作的FOP疗法，也是该病第二个获批药物，推荐起始剂量10mg/kg每月一次静脉输注。此前的另一款获批FOP药物为Incyte公司的Zlurgisertib（获批在即，9月PDUFA）。【事件3｜康希诺吸附破伤风疫苗获批+恒瑞连发四公告，国产创新与成人疫苗双线推进】 8月20日，康希诺公告吸附破伤风疫苗获国家药监局《药品注册证书》，用于非新生儿破伤风预防，并已与远大生命科学就大中华区独家推广达成商业化合作，标志着公司在成人疫苗市场再落一子。同日，舒泰神子公司江苏贝捷泰生物注射用STSP-0601（治疗伴抑制物血友病A或B患者出血，国家1类治疗用生物制品）获FDA临床试验许可，海外临床布局迈出关键一步。二、药品注册动态2.1 中国 NMPA/CDE 动态 ·【批准】NMPA批准成都盛迪医药（恒瑞）富马酸立康可泮胶囊（HRS-5965，补体因子B抑制剂，PNH，8/20）；批准三生国健安弗利奇塔单抗注射液（皮下注射）上市（8/20），用于对非甾体抗炎药和/或秋水仙碱禁忌、不耐受或缺乏疗效，以及不适合反复使用类固醇激素的成人痛风性关节炎急性发作。 ·【批准】NMPA批准康希诺吸附破伤风疫苗（非新生儿破伤风预防，8/20），与远大生命科学达成独家商业化合作。 ·【临床获批】恒瑞SHR-8203注射液（创新型抗肿瘤药，晚期实体瘤，国内外无同类药上市）、SHR-7012注射液（皮肤型红斑狼疮，国内外暂无同靶点药物获批）获批临床试验（8/20）；上海谊众YXC-002（第四代EGFR激酶抑制剂）临床试验获批；海思科小分子镇痛新药HSK51155片获批临床。 ·【受理】步长制药控股子公司泸州步长生物BC008-1A注射液（重组抗PD-1/TIGIT人源化双抗）新增适应症临床试验申请获NMPA受理——联合贝伐珠单抗用于成人复发CNS WHO 4级脑胶质瘤（8/19，国内外尚无同靶点双抗获批，累计研发投入约1.15亿元）。 ·【审评趋势】2026年上半年CDE密集发布不批准/不予批准通知件：4月14日批次87个受理号（齐鲁诺西那生钠注射液、圣兆亮丙瑞林微球、人福右哌甲酯缓释胶囊、科伦比拉斯汀等），5月27日批次27个（百代苯磺酸氨氯地平颗粒2.2类、永泰生物EAL细胞疗法等）——5月20日《化学仿制药药学研究重大缺陷情形》《化学仿制药生物等效性研究重大缺陷情形》发布后，仿制药审评由“发补式”转向“一票否决式”，6条“重大缺陷”红线（药学3条+BE 3条）直接不予批准。 ·【再注册】药品注册证书、化学原料药批准证书有效期5年到期需再注册，《药品管理法实施条例》修订版（5/15施行）确立境外研制数据可用于注册、仿制药须选参比制剂对比研究等要求。2.2 美国 FDA 动态 ·【批准】FDA批准再生元Pasatru（garetosmab-grts）治疗进行性骨化性纤维发育不良（FOP，8/19，详见核心事件）；FDA批准Viatris低剂量雌激素避孕贴片Gwyn Lo（MR-100A-01，7/30）。 ·【PDUFA窗口·8月下旬】Deramiocel 8/22（Capricor，DMD心肌病BLA，AdCom 7/29会议9:3负面，Capricor正修订BLA）；MOLBREEVI（molgramostim吸入溶液）8/22；Ziihera（zanidatamab）8/25（HER2+一线胃食管腺癌sBLA优先审评）；bictegravir/lenacapavir单片 8/27（HIV，ARTISTRY-1/2）；Garetosmab 8/31（已提前批准）。 ·【PDUFA窗口·9月】levacetylleucine 9/19（共济失调-毛细血管扩张症，优先审评）；UX111 AAV基因疗法 9/19（MPS IIIA重报）；WINREVAIR（sotatercept）9/21（PAH，HYPERION标签更新）；zilganersen 9/22（Alexander病ASO）；zlurgisertib 9/26（FOP，Incyte/Mirum）；lirafugratinib 9/27（FGFR2+胆管癌，ORR 46.5%）；Ameluz PDT 9/28（浅表基底细胞癌）；relutrigine原9/27延期至12/27（SCN2A/SCN8A DEE）。 ·【仿制药】FDA发布《确定提交ANDA还是505(b)(2)申请》指南草案（8/18）；PMDA 8/7发布仿制药BE研究健康志愿者安全性Early Considerations指南（自杀意念、骨髓抑制、QT延长、ILD等风险管理框架）。 ·【透明化】FDA通过openFDA公开200余份历史CRL（约37%申请收到CRL，74%涉质量与生产问题）；FDA提出新规拟“消除市场申请存在本身即构成商业保密信息的推定”。2.3 欧盟 EMA／日本 PMDA 动态 ·【欧盟·CHMP会议】CHMP 8月17-20日会议在阿姆斯特丹召开（本期关注其审评意见发布）；EMA对daraxonrasib（转移性胰腺癌）继续分阶段审评（phased review），加速评估同时保持审评严谨性。 ·【欧盟·注册管理】EMA 8月12日更新短缺预防计划模板（SPP）及指南（8月），要求MAH为处方药建立并维护短缺预防计划，法律实施截止2027年中；欧盟包装和包装废弃物法规（PPWR）8/12起适用；CAPs强制使用PLM网络版eAF（9/1起）；EU eCTD v4.0验证标准v1.1发布（7/15适用）。 ·【欧盟·审评动态】CHMP 7月会议推荐12种新药+8项适应症扩展+3款负面意见（KemSu/Meplyffa/Qezzaqar）已在8/17-20报告覆盖；Icotyde（首个口服IL-23R银屑病药）、Susvimo（欧盟首个可再填充眼内植入剂）等获批后进入欧盟市场。 ·【日本·PMDA】台湾美时制药（Lotus）pomalidomide胶囊仿制药（1/2/3/4mg）获PMDA上市许可（8/19），为日本首波pomalidomide仿制药，将与Fuji Pharma合作上市，该品日本年销售额约1.55亿美元（IQVIA）；PMDA更新donanemab等药品说明书修订（8/17）；发布2025年度监管科学活动报告（8/7）。2.4 国际组织及其他国家动态各国注册法规／指南更新（重点） ·【WHO PQ】截至2026年6月，WHO PQ清单共1,139个产品：664个成品制剂（印度占59%）、193个API、282个疫苗（印度血清研究所72个，占1/4）；HIV/结核/疟疾占成品制剂74%。2026年EOI持续更新：结核药第23次（bedaquiline/pretomanid复方）、抗疟药第24次（儿童颗粒剂质量规范）、糖尿病第3次（人胰岛素及甘精等生物类似药常态化受理）、物质使用障碍首次（美沙酮、丁丙诺啡）、API第41次。 ·【PIC/S】PIC/S 7/30发布新版《确认与验证建议》PI 006-4（10/1生效，取代2007年PI 006-3），从26页扩至49页：回顾性验证不再被接受、连续验证批次数须科学论证（当前Annex 15三批要求被视为过渡性）、持续工艺验证（OPV）正式取代定期再验证、PQ取样频率提高（不得仅批首中尾）、统计处理升级（Cpk/Ppk/多变量SPC）；PIC/S与EMA持续推进Annex 15修订（扩展至原料药）及Annex 6（药用气体）概念文件。 ·【乌兹别克斯坦】第3848号《国家注册文件要求指令》6/4注册生效：注册档案须对齐ICH标准、强制披露GMO与朊病毒风险；第738号决议（2/26生效）新增知识产权合规前置——注册须取得司法部关于商标、外观设计等IP无侵权的意见；10/1起实施国际认证（WLA/ML4）认可登记。 ·【哈萨克斯坦】注册新规草案公开评议至8/13截止：将注册、再注册、定价、国家药品处方集编制整合为“一站式”公共服务（试点至2026/12/31），不新增制造商义务；哈萨克斯坦为EAEU成员，eCTD（EAEU格式）提交、GMP检查强制、2026年起药品征收增值税。 ·【沙特SFDA】罕见病药品新加速计划NADR 9/5生效（接受AI/ML、器官芯片等灵活证据）；SFDA 8/11全球首个批准BMS Zenbexus（iberdomide，RRMM）——“中东反向首发”标志案例；8/2批准礼来Foundayo（orforglipron，体重管理）；7/21暂停Tavneos（avacopan）注册；孤儿药认定持续（Gomekli NF1、GS1168 PKU）。 ·【蒙古】2026-2030年传统蒙药发展计划获政府批准（3/18）：改善药品注册、按GMP标准发展传统药生产、促进出口；国家药品参比实验室6月启用；2月与波兰药品注册办公室签署MOU强化注册监管合作。 ·【其他】俄罗斯第999号决议（8/10）收紧短缺简化注册的本地化要求；印度CDSCO发布进口药品通用提交格式指南1.0（8/4）；马来西亚DRGD第3版第12次修订；新加坡e-labelling扩展；英国MHRA微生物组药品立场文件（8/18）；欧盟PPWR包装法规8/12适用。药品拒绝注册公示汇总 ·【ITM-11（177Lu-edotreotide，GEP-NETs核药）】8月7日收到FDA CRL（8/10公告）——原因仅指向CMC缺陷与第三方商业化生产设施未决问题，FDA未对临床/非临床数据包及安全性提出任何质疑、不要求新增研究（III期COMPETE：mPFS 23.9 vs 14.1个月，p=0.022）；公司计划整改后重新提交NDA。此为继Lantheus 68Ga核药6月CRL后核药领域又一例“生产设施型”拒批。 ·【Deramiocel（CAP-1002，DMD心肌病细胞疗法）】FDA细胞组织基因治疗顾问委员会7/29以9:3反对（安全性信号），8/22 PDUFA决策临近，Capricor正修订BLA以回应AdCom关切，市场关注度极高。 ·【FDA CRL透明化案例】PharmaVoice分析最新一批14份CRL（7/10发布）：多数指向产品质量与设施缺陷，仅3份涉临床问题——Ascelia口服MRI造影剂Orviglance（图像读片方法学问题）、Galderma肉毒素竞品RelabotulinumtoxinA（分析方优化+设施缺陷，2023年即因CMC被拒）；此前AZ Safnero（SLE，数据质量）、GSK Exdensur（CRSwNP，疗效证据不足）亦为典型案例。 ·【CDE不予批准】2026上半年密集拒批延续：4/14批次87个受理号、5/27批次27个（含永泰EAL细胞疗法缺确证性试验、百代苯磺酸氨氯地平颗粒2.2类临床优势不足、齐鲁诺西那生钠注射液参比制剂/药学缺陷）；金陵药业碳酸司维拉姆干混悬剂（体外BE不支持，累计投入414.53万元）、尖峰集团复方托吡卡胺滴眼液（规格合理性）等收到不予批准通知书。WHO预认证／PIC/S动态 ·WHO PQ 2026年度评估会议日程：9月21-25日、11月23-27日（线上）；2026年起所有适用费用年递增10%（IVD年度维护费每产品$4,000上调至$4,400），费用豁免制度1/1起停止；WHO可依赖FDA/EMA等SRA GMP检查结论减免自身检查，已有SRA合规记录的工厂具效率优势。 ·PIC/S 57个参与机构；PI 006-4新版为检查员培训资源与行业指引（10/1生效），中国推进加入PIC/S进程中，该文件基本预示未来检查方向——无菌/原料药企业须按“前瞻/同步/OPV”三路径重构验证体系，清除“回顾性验证”历史品种。中亚／西亚／蒙古／土库曼斯坦等非主流市场动态 ·【土库曼斯坦】常山药业肝素钠注射液（注射剂5ml，有效期5年）获土库曼斯坦药品监督管理部门注册证书（8月，用于防治血栓等疾病），持续验证“本地代理+国家格式+俄语翻译”路径可行性；此前四川汇宇多西他赛/紫杉醇注射液、Venus多西他赛已获批。注册周期180个日历日（不含缴费/实验室分析/答复时间），证书有效期5年，再注册须提前3个月申请；PV法规草案仍在推进。 ·【中亚出海生态】义乌举办“中亚出海机遇分享会”（8/19）聚焦市场准入与合规；哈萨克“一站式”注册至2026年底、乌兹别克10/1国际认证认可登记——中亚市场正从“个案突破”走向“体系化准入”。 ·【沙特/中东】SFDA NADR罕见病加速计划（9/5）与Zenbexus“全球首个批准”案例表明中东监管机构正成为创新药全球首发候选地；海湾市场仍以eCTD+阿拉伯语标签+本地授权代表（SAR）为基本门槛，审评周期8-18个月。 ·【蒙古】传统蒙药2026-2030发展计划+参比实验室启用+波兰MOU，注册体系对标欧盟方向演进；进口药注册4年、国产2年有效期机制需注意；WHO GMP或Certificate Scheme文件为基本要求。三、医药研发进展与突破3.1 临床突破 ·【mRNA癌症疫苗】Moderna/默沙东intismeran autogene（V940/mRNA-4157）+Keytruda：INTerpath-001 III期RFS+DMFS双终点达标（高危黑色素瘤辅助治疗，全球首个mRNA癌症疗法III期阳性，8/19；Moderna单日涨177%——昨日已报道，本期纳入后续进展跟踪）。 ·【维立志博维利信（PD-L1/4-1BB双抗）】联合化疗一线NSCLC的II期摘要于WCLC官网发布：60例疗效可评估患者ORR 65.0%、DCR 95.0%，鳞癌亚组ORR 77.4%（DCR 96.8%），非鳞癌ORR 51.7%；基于3.6个月随访，更新数据将于9/14 WCLC口头报告（8/19-20）。 ·【Amylyx avexitide】减重术后低血糖LUCIDITY III期达标：2/3级低血糖事件复合发生率较安慰剂降55%，计划2026年底提交NDA（8/18，昨日已报道）。 ·【恒瑞】富马酸立康可泮（HRS-5965，补体因子B抑制剂）获批PNH——全新靶点“双通路”抑制血管内外溶血，罕见病领域重要突破（8/20）。3.2 重要交易与合作 ·【迪哲医药-AstraZeneca】舒沃替尼全球独家许可落地：6亿美元首付款+最高9亿美元里程碑+阶梯式特许权使用费（舒沃替尼为全球EGFR exon20ins NSCLC领域中美双突破性疗法认定核心创新药）；迪哲2026上半年营收5.23亿元（+47%），亏损大幅收窄（8/20）。 ·【礼来-Amplitude Therapeutics】共同开发传染病反式扩增RNA（taRNA）疫苗候选产品，Amplitude负责taRNA优化及部分临床前，礼来主导后续开发、生产、监管及商业化（8/19，财务条款未披露）。 ·【国药现代】拟现金4.06亿元收购国药集团国瑞药业51%股权（交易对方国药集团、国药控股、国药股份），消除同业竞争并丰富神经系统、抗感染等产品管线（8/19）。 ·【康希诺-远大生命科学】吸附破伤风疫苗大中华区独家商业化合作（8/20）。 ·【英矽智能-元码智药】共建下一代mRNA AI原生研发引擎：AI新抗原预测与序列设计、环状mRNA、靶向递送、自动化实验及智能制造，探索个体化肿瘤疫苗（8/20）。 ·【维立志博-LBL-051】Oblenio Bio（Aditum Bio旗下NewCo）行使LBL-051全球独家选择权，维立志博获一次性1000万美元不可退款费用——TCE平台自免领域临床进展获市场认可（8/19）。 ·【时安生物】完成近4亿元A轮系列融资（Pre-A轮蓝驰领投，A/A+轮IDG资本连续领投，阳光融汇联合领投），专注创新siRNA药物研发（8/20）。3.3 热门靶点与前沿技术 ·【mRNA个性化新抗原平台】INTerpath-001成功推动mRNA从传染病疫苗向肿瘤治疗迁移；默沙东/Moderna已有9项II/III期覆盖NSCLC、膀胱癌、肾癌；国内惠正奇、云顶新耀（EVM16，2026Q4启动IIT Ib）等布局跟进。 ·【AI制药】英矽智能上线虚拟衰老细胞（VAC）平台（8/20，多智能体架构、六大生物学尺度协同推理）；英矽-元码智药合作落地；AI驱动的新药研发从“靶点发现”走向“mRNA序列设计+智能制造”全链条。 ·【核药】ITM-11 CRL再次印证“生产设施即注册瓶颈”——放射性同位素供应、CDMO灌装、第三方设施合规成为核药申报核心风险点；177Lu核药赛道临床价值获Lancet背书（mPFS 23.9个月）。 ·【补体/罕见病】恒瑞HRS-5965获批PNH后，国内补体因子B抑制剂赛道已聚集诺华Fabhalta（2024）、朗来依适宁、海思科优可盼（2026）多款产品，罕见病领域竞争与差异化并存。四、国际注册策略启示与建议5.1 主流市场（FDA/EMA/PIC/S/WHO PQ）注册策略启示 ·【核药与生物制品“生产设施”已成CRL主因】ITM-11（第三方设施）、Lantheus 68Ga（同因）、Galderma肉毒素（分析方优化+设施）接连受挫——2026年FDA拒批以CMC/设施缺陷为主（74%）。启示：申报前须完成“FDA视角”预审计，覆盖自有及第三方生产场地，明确质量协议、设备验证证据链、数据完整性；核药企业应将同位素供应商、灌装CDMO、物流链纳入注册文件一体化管理，并预留备选产能。 ·【FDA透明化红利】openFDA公开200+份CRL+拟议规则（消除申请存在即商业保密推定）——申报前可系统对标历史缺陷库做差距分析，降低“重复踩坑”概率；关注GDUFA/PDUFA 2028-2032承诺函草案（本土生产费用激励、审评沟通优化）。 ·【欧盟注册-市场准入一体化】EMA短缺预防计划（SPP，2027年中强制）、JCA前置资格检查、9/1 CAPs强制PLM eAF、PPWR包装法规——欧盟注册文件须同步满足HTA与供应链合规要求，建议在CTD模块1阶段即纳入SPP与包装合规设计。 ·【PIC/S PI 006-4倒计时】10/1生效的新验证建议将重构检查预期：回顾性验证作废、验证批次数科学论证、OPV取代定期再验证、PQ取样频率提升——有老品种企业须立即盘点“回顾性验证”清单并启动OPV补数据，避免检查缺陷。 ·【WHO PQ策略】2026年EOI扩容（糖尿病胰岛素/生物类似药、SUD药物、MDR-TB新组合）为中国原料药与成品制剂企业打开增量空间；建议优先选择EOI清单品种、借助SRA GMP互认减免检查、走简化评估（90天）路径，同时关注费用年增10%与豁免取消的成本影响。5.2 非主流市场（中亚、西亚、东南亚、蒙古、南美等）注册策略建议 ·【土库曼斯坦】常山药业肝素钠获批验证路径：本地代理（必需）+国家格式档案+俄语翻译（部分文件）+180天审评+5年证书。建议国内仿制药/原料药企业以“已有国际市场注册证（CPP/自由销售证书）+WHO GMP+稳定数据”组合申报；注意说明书/标签可提交土库曼语/俄语/英语，PV法规草案即将落地需提前建立警戒体系；再注册提前3个月启动，避免证书空窗。 ·【乌兹别克斯坦】第738号（IP合规前置）、第3848号（ICH对齐+GMO/朊病毒披露）、10/1国际认证认可登记三线并行——建议以“ICH CTD格式+国际认证（FDA/EMA/WHO PQ）背书+本地代理”组合申报，享受认可程序红利；关注2027年GMP强制与2029年BE研究ICH对齐的时间表，提前布局本地BE实验室合作。 ·【哈萨克斯坦】EAEU统一注册（eCTD格式、GMP强制）与“一站式”试点并行——建议将哈萨克作为EAEU参照国（ref state）申报，一次注册覆盖白俄、亚美尼亚、吉尔吉斯；注意2026年药品增值税开征与DataMatrix追溯码强制要求对定价/包装的影响。 ·【沙特/中东】SFDA已从“跟随批准”转向“全球首发”（Zenbexus全球首个批准、RAID/NADR加速计划）——建议创新药企将沙特纳入全球首发序列评估；注册仍以eCTD+阿拉伯语标签+SAR本地代表为硬门槛，审评周期8-18个月需计入立项计划。 ·【蒙古】传统蒙药发展计划+参比实验室启用+波兰MOU（对标欧盟）——注册体系向国际标准演进，进口药注册有效期4年较短，建议以WHO GMP文件+参比实验室检测配合推进；单一来源采购法规（WHO标准为门槛）提示公立采购渠道价值。 ·【东南亚/南亚】马来西亚DRGD修订、新加坡e-labelling、印度CDSCO通用提交格式、越南Circular 32（10/1，5年数据独占）——建议统一以CTD+eCTD格式准备，一次申报多国复用；关注各国本地化/数据独占新规对仿制药窗口期的影响。5.3 跨市场趋势与风险预警 ·【罕见病与超罕见病赛道全球提速】FDA两日批准FOP（Pasatru）与GSDIa基因疗法（GENGLYCOS，昨日），叠加沙特NADR、中国罕见病药市场独占期（≤7年）——《药品管理法实施条例》确立——罕见病注册的全球协同窗口正在打开，建议按“美国FDA/欧盟+中东首发+中国纳入”多线并行策略布局。 ·【“生产合规”成为全球注册第一道闸门】从FDA（ITM/Galderma/恒瑞双艾）到俄罗斯（同日5项质量召回）再到CDE（一票否决），全球审评均向“质量导向”转向——出口企业须按目的地药典标准出厂检验、建立批次级合规追溯，避免“临床成功、生产失败”的注册路径中断。 ·【CDE“一票否决”重塑仿制药立项】6条重大缺陷红线（药学3条+BE 3条）实施后，仿制药与简单改剂型立项门槛大幅提高——建议转向高壁垒复杂制剂（微球、脂质体、纳米晶）、完整代谢产物研究、确证性临床证据支撑的立项逻辑，并建立申报前与CDE的沟通交流机制。 ·【监管联动与透明度双升】FDA公开CRL、欧盟Tavneos全球联动撤市、CDE密集拒批公示——监管透明度提升意味着“黑箱”减少，但上市后安全性信号（如日本PV→欧盟撤市）可能在数月内触发全球连锁反应，MAH须预置跨国PV信号监测与危机响应机制。五、本期总结与展望本期（8月20-21日）全球医药监管与研发呈现三条主线：一是中国创新药批量兑现——恒瑞1类新药富马酸立康可泮获批PNH（补体因子B抑制剂新靶点）、康希诺破伤风疫苗获批、迪哲舒沃替尼6亿美元首付出海，国产创新与成人疫苗双线推进；二是FDA罕见病审评持续高效——FOP新药Pasatru获批叠加9月多项罕见病PDUFA（UX111、levacetylleucine、zilganersen），超罕见病赛道全球提速；三是全球“质量导向”审评趋严——ITM-11核药因生产设施CRL、CDE上半年密集拒批、PIC/S PI 006-4新版10/1生效，生产合规能力已成为注册成败的第一道闸门。注册管理层面，乌兹别克ICH对齐+IP前置、哈萨克“一站式”、沙特NADR“中东首发”、WHO PQ EOI扩容（胰岛素/SUD/MDR-TB）等更新，为非主流市场准入提供了“国际认证认可+本地化合规”双轮驱动的路径；欧盟SPP短缺预防计划与PPWR包装法规则提示注册-供应链一体化合规的重要性。展望明日：关注8月22日Deramiocel（DMD心肌病，AdCom 9:3负面后BLA修订）与MOLBREEVI两项PDUFA决策、8月25日Ziihera（HER2+一线胃食管腺癌）、8月27日bictegravir/lenacapavir单片（HIV），以及维立志博维利信WCLC口头报告（9/14）与Moderna/默沙东监管沟通进展。免责声明本报告基于公开可检索信息自动汇编生成，信息来源包括各国监管机构官网（NMPA/CDE、FDA、EMA、PMDA、SFDA、WHO、PIC/S等）及可靠专业媒体。报告内容仅供内部参考与行业交流，不构成任何投资建议、注册申报意见或法律意见。药品注册决策请以各国监管机构官方正式文件为准。

上市批准疫苗申请上市

2026-08-19

·BioSpace

IntraBio’s Pivotal Phase III Trial in CACNA1A-Related Disorders Is Enrolling and Is Expected to Be Over-Enrolled and Complete Recruitment in October

IB1001-304 is the first pivotal clinical trial conducted specifically for CACNA1A-related disorders , for which there are currently no approved therapies anywhere in the world. Recruitment for IB1001-304 has commenced; IntraBio anticipates the study will over-enroll and complete recruitment in October 2026. CACNA1A-related disorders have an incidence of approximately 1 in 11,700, corresponding to more than 30,000 individuals in the United States alone and an estimated 690,000 worldwide. IB1001-304 uses the same pivotal trial design that supported FDA approval and European Commission authorization of levacetylleucine (AQNEURSA®) in Niemann-Pick disease type C. AUSTIN, Texas--(BUSINESS WIRE)--IntraBio Inc., a global biopharmaceutical company developing and commercializing therapies for rare and common neurological diseases, today announced that its pivotal Phase III IB1001-304 trial evaluating levacetylleucine in individuals with CACNA1A-related disorders is enrolling. The company anticipates the study will over-enroll and complete recruitment in October 2026, with the trial designed to take 6-months to complete. IB1001-304 is the first pivotal clinical trial conducted specifically for CACNA1A-related disorders. The study uses the same design as the pivotal trial that supported U.S. FDA approval and European Commission authorization of levacetylleucine (AQNEURSA®) for the neurological manifestations of Niemann-Pick disease type C (NPC), and that supported IntraBio’s positive Phase III study in Ataxia-Telangiectasia (A-T). The supplemental New Drug Application for A-T is currently under FDA Priority Review, with a PDUFA target action date of September 19, 2026. “This trial marks a pivotal milestone for the CACNA1A community,” said Lisa Manaster, Co-Founder and President of the CACNA1A Foundation. “As the mother of a daughter living with a CACNA1A-related disorder, I know firsthand what it means to have real hope that we are moving closer to having an approved, safe, and effective treatment. Given the urgent unmet need our families face, we look forward to continuing to collaborate with IntraBio to help ensure this novel treatment is rapidly made available to patients in our community.” CACNA1A-related disorders refer to a group of rare, inherited neurological conditions. Despite the severity and lifelong course of these conditions, there are currently no approved therapies indicated for CACNA1A-related disorders anywhere in the world. The estimated incidence of CACNA1A-related disorders is approximately 1 in 11,700, corresponding to approximately 30,000 individuals in the United States alone and an estimated 690,000 worldwide. About IB1001-304 IB1001-304 is a multinational, randomized, double-blind, placebo-controlled crossover Phase III clinical trial evaluating levacetylleucine in individuals aged four years and older with genetically confirmed CACNA1A-related disorders. The trial is being conducted at multinational sites in Austria, Germany, Greece, Italy, Switzerland, the United Kingdom and the United States. Further information about IB1001-304, including participating locations and eligibility requirements, is available at ClinicalTrials.gov under study NCT07221292. The study is registered on ClinicalTrials.gov as NCT07221292 and under EU CT Number 2025-523828-51. Levacetylleucine is investigational for the treatment of CACNA1A-related disorders and has not been approved by the FDA, MHRA, European Commission, Swissmedic or any other regulatory authority for this indication. About CACNA1A-Related Disorders CACNA1A-related disorders are rare, inherited neurological conditions caused by pathogenic variants in the CACNA1A gene, which plays a central role in calcium-channel function within the nervous system. Symptoms can begin in infancy, childhood or adulthood. The estimated incidence of CACNA1A-related disorders is approximately one in 11,700. There are currently no approved therapies indicated for CACNA1A-related disorders. About AQNEURSA® (levacetylleucine) U.S. Indication AQNEURSA® (levacetylleucine) is indicated in the United States for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adults and pediatric patients weighing at least 15 kg. U.S. IMPORTANT SAFETY INFORMATION Embryo-Fetal Toxicity Based on findings from animal reproduction studies, AQNEURSA may cause embryo-fetal harm when administered during pregnancy. The decision to continue or discontinue AQNEURSA during pregnancy should consider the patient’s clinical need, the potential drug-related risks to the fetus, and the potential adverse outcomes from untreated maternal disease. Pregnancy and Lactation: For females of reproductive potential, confirm the patient is not pregnant prior to initiating treatment. Advise use of effective contraception during treatment and for 7 days after the last dose if AQNEURSA is discontinued. There are no data on the presence of levacetylleucine or its metabolites in human or animal milk; the developmental and health benefits of breastfeeding should be weighed against clinical need and potential risks to the infant. Adverse Reactions The most common adverse reactions (incidence ≥5% and greater than placebo) are abdominal pain, dysphagia, upper respiratory tract infections, and vomiting. Drug Interactions Avoid concomitant use of AQNEURSA with N-acetyl-DL-leucine or N-acetyl-D-leucine. The D-enantiomer competes with levacetylleucine for monocarboxylate transporter uptake, potentially reducing efficacy. Monitor more frequently for P-gp substrate-related adverse reactions when used concomitantly with AQNEURSA, as AQNEURSA inhibits P-gp; the clinical significance of this finding has not been fully characterized. To report SUSPECTED ADVERSE REACTIONS, contact IntraBio Inc. at 1-833-306-9677 or FDA at 1-800-FDA-1088 or visit . Please see Full U.S. Prescribing Information for AQNEURSA at aqneursahcp.com . EU (EMA) Indication AQNEURSA® is authorized in the European Union for the treatment of neurological manifestations of Niemann-Pick disease type C, in combination with miglustat or as a monotherapy in patients where miglustat is not tolerated, in adults and children aged 6 years and older and weighing at least 20 kg. See EMA Indication and Important Safety Information: About IntraBio IntraBio Inc. is a global biopharmaceutical company headquartered in Austin, Texas, focused on developing and commercializing targeted therapies for rare and common neurological, neurodevelopmental and mitochondrial diseases. IntraBio’s platform technologies are built on decades of scientific research and collaboration with leading institutions worldwide. Forward-Looking Statements This press release contains forward-looking statements, including statements regarding the anticipated pace and completion of enrollment in IB1001-304, the expected timing on which the study will close to further participants, the potential of levacetylleucine in CACNA1A-related disorders and other indications, and the anticipated timing of regulatory action. These statements are based on IntraBio’s current expectations and are subject to risks and uncertainties, including the pace of patient identification and screening, site activation timelines, and regulatory and clinical developments. Actual results may differ materially. IntraBio undertakes no obligation to update any forward-looking statement except as required by law. Contacts MEDIA & INVESTOR CONTACT Cass Fields Vice President, External Affairs ccfields@intrabio.com

100 项与 N-乙酰-L-亮氨酸相关的药物交易

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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
神经系统表现	欧盟	Intrabio Ireland Ltd.	2026-01-19
神经系统表现	冰岛	Intrabio Ireland Ltd.	2026-01-19
神经系统表现	列支敦士登	Intrabio Ireland Ltd.	2026-01-19
神经系统表现	挪威	Intrabio Ireland Ltd.	2026-01-19
C型尼曼匹克病	美国	Intrabio Ireland Ltd.	2024-09-24
C型尼曼匹克病	美国	IntraBio, Inc.	2024-09-24

未上市

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适应症	最高研发状态	国家/地区	公司	日期
共济失调毛细血管扩张	申请上市	美国	IntraBio, Inc.	2026-03-20
阵发性共济失调2型	临床3期	美国	IntraBio Ltd.	2026-08-17
阵发性共济失调2型	临床3期	奥地利	IntraBio Ltd.	2026-08-17
阵发性共济失调2型	临床3期	德国	IntraBio Ltd.	2026-08-17
阵发性共济失调2型	临床3期	希腊	IntraBio Ltd.	2026-08-17
阵发性共济失调2型	临床3期	意大利	IntraBio Ltd.	2026-08-17
阵发性共济失调2型	临床3期	瑞士	IntraBio Ltd.	2026-08-17
阵发性共济失调2型	临床3期	英国	IntraBio Ltd.	2026-08-17
家族性1型偏瘫性偏头痛	临床3期	美国	IntraBio Ltd.	2026-08-17
家族性1型偏瘫性偏头痛	临床3期	奥地利	IntraBio Ltd.	2026-08-17

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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


IB1001-301 (EAN2026)	临床3期	C型尼曼匹克病	40	N-acetyl-L-leucine (NALL) (Extension Phase (open-label))	網積繭觸糧願壓窪餘艱(醖觸簾願範夢築齋製網) = 衊簾鏇餘壓醖繭餘憲鏇餘鹹鬱膚窪鑰憲鏇鏇醖 (鬱膚衊壓蓋獵蓋繭顧鹽, 4.0)	积极	2026-06-26
				Placebo	廠鏇簾鬱壓構積襯糧廠(夢餘糧選鹽鏇簾襯觸襯) = 艱鏇製獵積簾繭淵艱鹽願廠餘膚鹹襯繭鏇餘醖 (壓艱築簾鑰繭願網簾膚, 7.9) 更多
S31.004 (AAN2025)	临床3期	C型尼曼匹克病	60	Levacetylleucine	夢觸獵衊廠繭觸鑰醖簾(網鏇夢糧願壓製襯製窪) = On each mDRS domain there was improvement from baseline when patients received levacetylleucine and a greater improvement in each domain when patients were treated with levacetylleucine versus placebo 淵願壓衊鹹衊廠顧衊膚 (糧網餘製觸遞壓艱壓顧 ) 更多	积极	2025-04-07
				Placebo
NCT05163288 (FDA_CDER) 人工标引	临床3期	C型尼曼匹克病	60	AQNEURSA	積觸觸構膚築製範醖膚(艱鬱積壓壓蓋襯遞範鹹) = 醖醖淵夢夢構廠憲積獵淵餘艱獵鏇鹹網廠蓋蓋 (鑰壓觸鏇顧願糧製鏇夢, 0.1)	积极	2024-09-24
				Placebo	積觸觸構膚築製範醖膚(艱鬱積壓壓蓋襯遞範鹹) = 醖窪艱衊憲衊糧繭顧窪淵餘艱獵鏇鹹網廠蓋蓋 (鑰壓觸鏇顧願糧製鏇夢, 0.1)
NCT03759665 (Accesswire) 人工标引	临床2期	GM2神经节苷脂贮积症	30	IB1001	憲襯構窪獵築窪鑰廠壓(構夢膚艱選範觸鏇積鑰) = statistically significant change. 90% CI: 0.00, 1.50, p-value = 0.039 窪築構簾願獵膚鹽淵鏇 (醖簾艱簾壓繭淵鬱淵鹽 ) 更多	积极	2021-09-14
NCT03759639 (Pubmed \| J Neurol) 人工标引	临床2期	C型尼曼匹克病	32	N-acetyl-L-leucine	簾製鬱鬱醖艱夢廠繭夢(夢簾醖廠觸鏇齋鏇齋醖) = NALL met the CI-CS primary endpoint (mean difference 0.86, SD = 2.52, 90% CI 0.25, 1.75, p = 0.029) 淵鹽鏇範積齋鑰膚齋憲 (鬱選積鑰鑰鬱壓餘鏇構 )	积极	2021-08-13
NCT00768287 (CTgov)	临床2/3期	血友病B	77	IB1001 (IB1001)	製獵範鹽願襯鬱齋淵選(窪壓顧餘醖膚簾鬱網積) = 獵獵選選憲獵艱簾艱襯鏇顧窪願醖齋醖選簾願 (壓衊糧膚艱糧範鑰窪鹹, 451.5) 更多	-	2018-09-10
				nonacog alfa (Nonacog Alfa)	製獵範鹽願襯鬱齋淵選(窪壓顧餘醖膚簾鬱網積) = 衊窪醖衊願範鹽壓蓋壓鏇顧窪願醖齋醖選簾願 (壓衊糧膚艱糧範鑰窪鹹, 468.6) 更多