A Phase I, Single Centre, Randomised, Interventional, Open-Label, Cross-Over Study to Evaluate the Pharmacokinetics (PK) and the Safety and Tolerability of a Total Daily Dose of 900mg of TETA 4HCL, Comparing a New Once Daily TETA 4HCL Formulation (300mg) (3x300mg Trientine Base Tablets, OD) With the Current Marketed Cuprior® Formulation (150mg) (3x150mg Trientine Base Tablets, BD) in Adult Healthy Male and Female Participants

A randomised, open-label study evaluating the pharmacokinetics, safety, and tolerability of a new once daily dose of 900mg of TETA 4HCL by comparing it against the current marketed Cuprior® formulation (450mg trientine base, twice daily) in healthy male and female participants.

开始日期2024-01-16

申办/合作机构

Orphalan SA

DRKS00028305N/A

Prospective, descriptive, non-interventional, German multicenter study to evaluate the quality of life of Wilson disease patients after switching from D-penicillamine to trientine tetrahydrochloride and to assess clinical and patient reported outcomes - PACUS

开始日期2022-04-01

申办/合作机构-

IRCT20200105046010N34 / Recruiting

In- Vivo Bioequivalence study of Trientine hard capsules 250 mg with brand drug (CYPRINE® 250 mg Merck & Co., Germany) in Iranian healthy volunteers.

开始日期2021-07-01

申办/合作机构-

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项与四盐酸曲恩汀相关的文献（医药）

2024-05-01·Hepatology (Baltimore, Md.)

Effects of trientine and penicillamine on intestinal copper uptake: A mechanistic 64Cu PET/CT study in healthy humans

Article

作者: Munk, Ditte Emilie ; Sandahl, Thomas Damgaard ; Kirk, Frederik Teicher ; Swenson, Eugene Scott ; Quicquaro, Adam Michael ; Vendelbo, Mikkel Holm ; Ott, Peter ; Schilsky, Michael L

Background and Aims::

Trientine (TRI) and D-penicillamine (PEN) are used to treat copper overload in Wilson disease. Their main mode of action is thought to be through the facilitation of urinary copper excretion. In a recent study, TRI was noninferior to PEN despite lower 24-hour urinary copper excretion than PEN. We tested whether TRI and/or PEN also inhibit intestinal copper absorption.

Approach and Results::

Sixteen healthy volunteers were examined with positron emission tomography (PET)/CT 1 and 15 hours after an oral Copper-64 (64Cu) dose. They then received 7 days of either PEN or TRI (trientine tetrahydrochloride), after which the 64Cu PET/CT scans were repeated. Venous blood samples were also collected. Pretreatment to posttreatment changes of the hepatic 64Cu uptake reflect the effect of drugs on intestinal absorption. 64Cu activity was normalized to dose and body weight and expressed as the mean standard uptake value. TRI (n=8) reduced hepatic 64Cu activity 1 hour after 64Cu dose from 6.17 (4.73) to 1.47 (2.97) standard uptake value, p<0.02, and after 15 hours from 14.24 (3.09) to 6.19 (3.43), p<0.02, indicating strong inhibition of intestinal 64Cu absorption. PEN (n=8) slightly reduced hepatic standard uptake value at 15 hours, from 16.30 (5.63) to 12.17 (1.44), p<0.04.

Conclusions::

In this mechanistic study, we show that TRI inhibits intestinal copper absorption, in addition to its cupriuretic effect. In contrast, PEN has modest effects on the intestinal copper absorption. This may explain why TRI and PEN are equally effective although urinary copper excretion is lower with TRI. The study questions whether the same therapeutic targets for 24-hour urinary excretion apply to both drugs.

2023-02-01·Journal of gastroenterology and hepatology

Experience on switching trientine formulations in Wilson disease: Efficacy and safety after initiation of TETA 4HCl as substitute for TETA 2HCl

Article

作者: Morgil, Müzeyyen ; Poujois, Aurelia ; Mohr, Isabelle ; Morvan, Erwan ; Bourhis, Hélène ; Denk, Gerald ; Woimant, France ; Merle, Uta ; Weiss, Karl Heinz ; Obadia, Mickael Alexandre

Abstract:

Background and Aim:

This retrospective, multicenter study aims to assess the efficacy and safety in Wilson disease (WD) patients treated with trientine tetrahydrochloride (TETA 4HCl) after switch from trientine dihydrochloride (TETA 2HCl).

Methods:

In total, 68 WD patients with stable copper metabolism were identified to receive TETA 4HCl (Cuprior™) after previous treatment with TETA 2HCl. We analyzed biochemical markers such as urinary copper, serum copper, non‐coeruloplasmin bound copper (NCC), and transaminases as well as clinical scores (APRI; FIB‐4 score) at baseline with a follow‐up (FU) of 12 months. Safety of TETA 4HCl treatment was based on reported adverse events (AEs).

Results:

The study cohort reflects a common WD cohort with a mean age of 20.3 years at diagnosis and 38.3 years at baseline. There are no significant differences concerning serum copper, NCC, transaminases, APRI, and FIB‐4 score in the 3‐month FU. Six‐month FU revealed a decreased AST (P = 0.008), APRI (P = 0.042), and FIB‐4 score (P = 0.039). GGT varied only borderline significantly in the 3‐month, but not in the 6‐month FU. Comparison of urinary copper within the subsets did not reveal a difference to baseline in all FUs, suggesting stable control of copper metabolism. Few AEs during TETA 4HCl treatment were reported, most commonly gastrointestinal discomfort. Only three treatments with TETA 4HCl were discontinued.

Conclusion:

Copper parameters and liver function were stable after treatment switch to TETA 4HCl. Treatment with TETA 4HCl was generally well tolerated. This study indicates that the switch from TETA 2HCl to TETA 4HCl is safe and viable.

2022-12-01·The lancet. Gastroenterology & hepatology

Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial

Article

作者: To, Uyen ; Ala, Aftab ; Dubois, Nicolas ; Obadia, Alexandre ; Lachaux, Alain ; Czlonkowska, Anna ; Sandahl, Thomas D ; Weiss, Karl Heinz ; Belmalih, Abdelouahed ; Denk, Gerald ; Schilsky, Michael L ; Cury, Rubens G ; Piechal, Agnieszka ; Patel, Amar ; Langel, Andrea ; Moore, Joanna ; Litwin, Tomasz ; Cassiman, David ; Gerdes, Lisbet ; Mohr, Isabelle ; Couchonnal-Bedoya, Eduardo ; Monico, Sara ; Barbosa, Egberto Reis ; Poujois, Aurelia ; Freitas, Christian ; Cosgrove, Jeremy ; Boogers, Alexandra ; Ott, Peter ; Twardowschy, Carlos ; Giorgini, Alessia ; Hettiarachchi, Daksshi ; Rahli, Djamila ; D'Hollander, Koenraad ; Zuin, Massimo ; Kamlin, C Omar F ; D'Inca, Renata ; Gondim, Francisco de Assis A ; Skowronska, Marta

BACKGROUND:

Wilson disease is an inherited disorder of copper transport. Whereas penicillamine is used therapeutically to re-establish copper balance, trientine is indicated for patients with penicillamine intolerance. We aimed to compare penicillamine with trientine tetrahydrochloride (TETA4) for maintenance therapy in patients with Wilson disease.

METHODS:

We conducted a randomised, open-label, non-inferiority, phase 3 trial at 15 health-care centres across nine countries (patients were recruited from 13 of these health-care centres across Brazil, Europe, and the USA). We enrolled patients aged 18-75 years with stable Wilson disease who were treated for at least 1 year with penicillamine. Patients entered a 12-week period to determine stability through clinical assessment by site investigators and predefined thresholds for serum non-caeruloplasmin-bound copper (NCC; by an exchangeable copper assay; 25-150 μg/L), 24 h urinary copper excretion (100-900 μg/24 h), and alanine aminotransferase (ALT; <2 × upper limit of normal). Stable patients were randomly assigned (1:1) to continue receiving the maintenance twice daily dose of oral penicillamine or switched mg-for-mg to oral TETA4 centrally with a web-based system using minimisation. The primary endpoint, assessed 24 weeks after randomisation, was NCC by speciation assay. The non-inferiority margin of mean difference in NCC by speciation assay was -50 μg/L, as estimated by a general linear model for repeated visits, adjusted for baseline values. Further data on safety and efficacy were collected during a 24-week extension period. Data were analysed using an intention-to-treat approach. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03539952 (active, not recruiting).

FINDINGS:

Between June 4, 2018, and March 10, 2020, 77 patients were screened. 53 patients were randomly assigned (27 to the penicillamine group and 26 to the TETA4 group). After 24 weeks, the mean difference in serum NCC by speciation assay between the penicillamine group and TETA4 group was -9·1 μg/L (95% CI -24·2 to 6·1), with the lower limit of the 95% CI within the defined non-inferiority margin. At 24 weeks, urinary copper excretion was lower with TETA4 than with penicillamine (mean difference 237·5 μg/24 h (99% CI 115·6 to 359·4). At 48 weeks, TETA4 remained non-inferior to penicillamine in terms of NCC by speciation assay (mean difference NCC -15·5 μg/L [95% CI -34·5 to 3·6]). Urinary copper excretion at 48 weeks remained in the expected range for well treated patients in both study groups, and the mean difference (124·8 μg/24 h [99% CI -37·6 to 287·1]) was not significantly different. At 24 weeks and 48 weeks, masked clinical adjudication of stability assessed by three independent clinicians confirmed clinical stability (100%) of all participants, in agreement with the stability seen with the NCC by speciation assay. There were no notable changes in either the Clinical Global Impression of Change or Unified Wilson Disease Rating Scale (neurological assessment) from baseline (pre-randomisation) at weeks 24 and 48. The mean change in serum total copper from baseline to 24 weeks was 17·6 μg/L (99% CI -9·5 to 44·7) with penicillamine and -6·3 μg/L (-34·7 to 22·1) with TETA4, and the mean change in serum total caeruloplasmin from baseline to 24 weeks was 1·8 mg/L (-19·2 to 22·8) with penicillamine and -2·2 mg/L (-6·1 to 1·7) with TETA4. All liver enzymes were similar at 24 weeks and 48 weeks, with the exception of elevated ALT concentration at 48 weeks for patients in the TETA4 group. Penicillamine was associated with three post-randomisation serious adverse events (leukopenia, cholangiocarcinoma, and hepatocellular cancer); none were reported for TETA4. The most common treatment-emergent adverse events were headache for penicillamine (five [19%] of 27 patients vs two [8%] of 26) and abdominal pain for TETA4 (one [4%] vs four [15%]); all treatment-emergent adverse events resolved and were mild to moderate. One patient developed a rash with TETA4 that resolved on discontinuation of therapy.

INTERPRETATION:

The efficacy of TETA4 as oral maintenance therapy was non-inferior to penicillamine and well tolerated in adults with Wilson disease.

FUNDING:

Orphalan.

项与四盐酸曲恩汀相关的新闻（医药）

2024-02-21

·医药观澜

针对致命罕见病！诺贝仁医药「醋酸锌片」在中国获批上市

2月19日，中国国家药监局（NMPA）官网最新公示，由诺贝仁制药（Nobelpharma）公司申报的5.1类新药醋酸锌片上市申请已获得批准。醋酸锌片是一种铜吸收抑制剂。根据中国国家药监局药品审评中心（CDE）优先审评公示，该产品本次获批的适应症为肝豆状核变性。公开资料显示，肝豆状核变性（又称Wilson病，威尔逊病）是一种罕见的遗传性疾病。在正常情况下，肝脏可以通过将过量的铜随胆汁排出而维持体内铜的平衡。但在肝豆状核变性患者中，遗传突变使这种胆汁排泄途径失效，导致过量的铜在肝细胞中累积，并最终超过身体的安全储存能力，引起细胞损伤。当铜的积累超过肝脏的储存能力并引起肝脏细胞受损时，这些铜会释放到血液中，并可能在其它器官积累，包括中枢神经系统。如果不治疗，该病会导致严重的肝脏、神经和精神症状，甚至可能致命。肝豆状核变性主要治疗措施是排除蓄积在体内各种组织的铜，目前常用的药物有螯合剂（如青霉胺、曲恩汀）和锌制剂。研究表明，锌制剂既能阻止铜在肠道的吸收，也能清除沉积于组织中的铜，可作为该疾病的治疗方式之一。根据诺贝仁医药公开资料，醋酸锌片（zinc acetate，商品名为Nobelzin）是一款铜吸收抑制剂，已经在日本获批上市，用于治疗肝豆状核变性、低锌血症。 2023年2月，诺贝仁医药递交的醋酸锌片上市申请因“符合儿童生理特征的儿童用药品新品种、剂型和规格”被CDE纳入优先审评，拟用于治疗肝豆状核变性。该药本次获批意味着中国的肝豆状核变性患者将拥有新的治疗选择。参考资料： [1]2024年02月19日药品批准证明文件送达信息发布. Retrieved Feb 19，2024, From https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20240219145247178.html [2]诺贝仁医药官网. From https://www.nobelpharma.co.jp/cn/story/develop_melatobel/ [3]诺贝仁医药产品管线. From https://www.nobelpharma.co.jp/cn/research/product/ 内容来源于网络，如有侵权，请联系删除。

优先审批上市批准

2024-01-18

·GlobeNewswire-Health Care

Orphalan announces China NMPA’s approval of its trientine tetrahydrochloride product for the treatment of Wilson disease

Orphalan announces China NMPA’s approval of its trientine tetrahydrochloride product for the treatment of Wilson disease Paris, France 18 January, 2024 - Orphalan SA (“Orphalan” or “the Company”), an international orphan drug development and commercialization company, today announces the approval of its trientine tetrahydrochloride product by China's National Medical Products Administration (NMPA). This product, already marketed as Cuprior® in the EU, the UK, Saudi Arabia, Switzerland, and Colombia, and as Cuvrior® in the US, represents the first trientine approved by the NMPA. It offers a new treatment option for Wilson disease in children aged five years and older and adults intolerant to penicillamine therapy. China is home to an estimated 80,000 individuals with Wilson disease, of whom approximately half have their diagnosis confirmed, and 25,000 are receiving regular treatment. The introduction of new treatment alternatives such as Orphalan’s trientine tetrahydrochloride, particularly for patients who are intolerant to currently available therapies, presents a significant opportunity to meet the needs of a broader segment of the Wilson disease population in China. Orphalan anticipates its product to be available in the country in the coming months. Dr Naseem Amin, Chief Executive Officer at Orphalan, said: “We are pleased with the marketing authorisation approval of our trientine tetrahydrochloride product in China, which offers a well-tolerated and effective treatment option for patients with Wilson disease. This approval is a crucial step towards providing a much-needed treatment option for the Wilson disease community in China and reaffirms our commitment to improving the experience for patients living with rare diseases worldwide.” Yan Qin, Director of Wuhan Tongxin (Wilson disease patient group in China) added: “We were thrilled when we heard that NMPA approved Orphalan's trientine tetrahydrochloride in China. It is a significant step for those of us living with Wilson disease, representing a much-needed alternative treatment option. This approval, a result of Orphalan's patient-focused approach, offers us a chance to better manage our condition with a new, effective treatment.” Wilson disease is a rare inherited disorder of copper transport primarily affecting the liver and brain. Early treatment with legacy agents such as D-penicillamine (DPA), trientine HCI, and zinc salts can effectively slow the progression of the disease, however these options may not be suitable for long-term care due to adverse events associated with DPA and the need for close monitoring during treatment with zinc salts and DPA. ENDS About Orphalan Orphalan is an international orphan drug development and commercialization company headquartered in Paris. Founded in 2011, the Company develops and deliver innovative therapies for people living with rare and debilitating diseases. Our trientine tetrahydrochloride product has been approved for the treatment of Wilson disease and is available in more than 20 countries, branded as Cuprior® in EU, the UK, Saudi Arabia, Switzerland and Columbia, and as Cuvrior® in the United States. For more information visit www.orphalan.com and follow us on LinkedIn. For more information, please contact: Orphalan: Géraldine van den Broek, Head of Corporate & BD Tel: +33 (0)1 42 49 82 64 info@orphalan.com ICR Consilium: Tracy Cheung, Sukaina Virji, Davide Salvi Tel: +44 (0) 203 709 5700 orphalan@consilium-comms.com

上市批准孤儿药

2024-01-07

·E药经理人

E周药闻 | 罗氏开年三笔大BD；MNC收购中国Biotech又添一例；医保局对全国药价调整再出手！

好不热闹！罗氏开年三笔大BD，直接把新年火热氛围拉满，牵手宜联生物、Remix Therapeutics、MOMA Therapeutics三家Biotech展开合作，总金额达40亿美元。更多MNC加入扫货队伍。年初，在华“扫货大户”阿斯利康引进了安锐医药开发的EGFR L858R变构抑制剂；BI则看向了瑞博生物，与其共同开发治疗非酒精性或代谢功能障碍相关脂肪性肝炎的小核酸创新疗法；备受青睐的还有安锐生物，开年便接连授权两款产品，金额超10亿美元。不止BD，诺华收购信瑞诺医药则为这份热闹再添了一把火。这是继阿斯利康2023年年末收购中国CAR-T疗法公司亘喜生物后，MNC收购中国Biotech的第二例。一则通知更是拉开了2024年全国药品价格调整的序幕。医保局要求，2024年3月底前，各省对挂网药品进行价格治理，实现同通用名、同厂家、同剂型、同规格药品在各省消除不公平高价、歧视性高价。新年伊始，场面一度打得火热，着实为久挥不去的资本寒冬增添了一些热气。此外，本周还有哪些值得关注的消息？政策动态医保局：3月底，各省对挂网药品进行价格治理1月5日，国家医保局发布《关于促进同通用名同厂牌药品省际间价格公平诚信、透明均衡的通知》。文件表示，目前各地按部署完成统一数据信息、实行数据分区、落实分区管理等基础任务，但分析发现少数企业少数药品存在利用省际间信息差实行不公平高价、歧视性高价问题，所以国家医保局下发通知，要求2024年3月底前，各省对挂网药品进行价格治理，实现同通用名、同厂家、同剂型、同规格药品在各省消除不公平高价、歧视性高价。又一厅官落马！曾历任贵州省卫生厅、食药监、医保局一把手1月2日，据贵州省纪委监委消息，贵州省人大社会建设委员会主任委员宋宇峰涉嫌严重违纪违法，目前正接受纪律审查和监察调查。公开资料显示，宋宇峰出生于1962年6月，贵州贵阳人，毕业于华西医科大学口腔医学院，早年从医，是一位口腔医学领域的专家，后来历任贵阳医学院院长、贵州省卫生厅厅长、贵州省食药监局局长、贵州省医保局局长等职。大型制药上药第一生化再被医保局约谈1月4日，医保局发布消息，国家医保局根据工作安排和相关部门查实的价格虚高事实，再次约谈上药第一生化，督促进一步纠正不合理高价，剔除药品价格虚高空间，消除不良影响。经约谈，上药第一生化承诺将注射用硫酸多黏菌素B挂网价格从270元/支进一步降低至123元/支，并保证稳定供应。罗氏抗流感新药玛巴洛沙韦干混悬剂在中国获批上市1月5日，国家药监局官网最新公示，罗氏抗流感新药玛巴洛沙韦干混悬剂的上市申请已正式获批。根据CDE官网优先审评公示，该上市申请针对适应证为：适用于儿童单纯性甲型和乙型流感患者，包括既往健康的患者以及存在流感并发症高风险的患者。公开资料显示，玛巴洛沙韦是一款创新单剂量口服药物，其片剂此前已经在中国获批。葛兰素史克抗IL-5单抗在华获批新适应证1月2日，国家药监局官网最新公示，GSK公司美泊利珠单抗（mepolizumab，商品名：新可来）注射液的新增适应证上市申请已被正式批准，该药本次获批作为一种联合维持疗法用于治疗重度嗜酸粒细胞性哮喘。阿斯利康引进安锐医药EGFR L858R变构抑制剂1月2日，Allorion Therapeutics（安锐医药）宣布，已与阿斯利康签订独家选择权和全球许可协议，以开发和商业化新型表皮生长因子受体（EGFR）L858R突变变构抑制剂，作为晚期EGFR突变非小细胞肺癌（NSCLC）的潜在新疗法。根据协议条款，阿斯利康将获得一种新型EGFR L858R变构抑制剂的独家选择权，获得其在全球开发和商业化的权利。Allorion有资格获得高达4000万美元的前期和近期付款，以及超过5亿美元的额外开发和商业里程碑付款。诺华押注新型基因治疗1月2日，Voyager Therapeutics宣布与诺华制药子公司Novartis Pharma AG达成战略合作和衣壳许可协议，推进亨廷顿舞蹈症（HD）和脊髓性肌萎缩（SMA）的潜在基因疗法。Voyager将向诺华提供使用Voyager TRACER™衣壳的独家许可和其他知识产权，Voyager和诺华将合作开发亨廷顿舞蹈症（HD）的临床前基因治疗候选药物。阿斯利康/赛诺菲乐唯初在华获批上市1月2日，阿斯利康与赛诺菲共同宣布长效单克隆抗体乐唯初（Nirsevimab/尼塞韦单抗）正式获得国家药监局批准上市，用于预防新生儿和婴儿由呼吸道合胞病毒（RSV）引起的下呼吸道感染（LRTI）。该药物适用于即将进入或出生在第一个RSV感染季的新生儿和婴儿。1尼塞韦单抗预计将于2024-2025年RSV感染季在中国上市。罗氏皮下注射乳腺癌组合疗法在华获批上市1月2日，国家药监局官网最新公示，罗氏递交的帕妥珠曲妥珠单抗注射液（皮下注射）新药上市申请已正式获批。公开资料显示，这是一款固定剂量组合的皮下制剂（商品名为Phesgo），此前已在美国、欧盟等国家和地区获批，用于治疗早期和转移性HER2阳性乳腺癌患者。与标准静脉给药的数小时相比，Phesgo可在5~8分钟内将帕妥珠单抗和曲妥珠单抗以更快的方式完成给药。恒瑞医药多款创新药获批上市1月3日，恒瑞医药发布公告，子公司成都盛迪医药有限公司收到国家药监局核准签发的《药品注册证书》，批准公司自主研发的醋酸阿比特龙片（II）上市，这是中国首个醋酸阿比特龙纳米晶制剂获批上市，也是恒瑞医药获批上市的第二个化学药品第2类新药。1月5日，国家药监局官网显示，恒瑞医药两款创新药盐酸伊立替康脂质体注射液和恒格列净二甲双胍缓释片均获批上市。其中，盐酸伊立替康脂质体适用于联合5-FU/LV二线治疗经吉西他滨治疗失败后局部晚期或转移性胰腺癌患者；恒格列净二甲双胍缓释片适用于适合接受脯氨酸恒格列净和盐酸二甲双胍治疗的2型糖尿病成人患者，以改善此类患者的血糖控制。恒瑞医药HER3 ADC获FDA快速通道资格1月1日，恒瑞医药宣布美国FDA授予SHR-A2009快速通道资格，用于治疗经三代EGFR酪氨酸激酶抑制剂和含铂化疗后疾病进展的EGFR突变的转移性非小细胞肺癌。SHR-A2009是恒瑞医药自主研发的一款HER3 ADC，可特异性结合肿瘤细胞表面上的HER3，进而被内吞至细胞内并转运至溶酶体中，水解释放游离毒素，杀伤肿瘤细胞。SHR-A2009于2021年进入临床研究，目前已经推进至II期临床。其治疗实体瘤的国际多中心I期临床研究正在中国、日本、韩国16家中心开展。初步研究结果显示，SHR-A2009具有良好的抗肿瘤活性、安全性和药代动力学特征。生物科技百济神州抗PD-1抗体在华获批第12项适应证1月2日，国家药监局官网最新公示，百济神州抗PD-1抗体替雷利珠单抗（商品名：百泽安）的新适应症上市申请已正式获批。根据百济神州早前公开资料，此次是替雷利珠单抗在中国获批的第12项适应证，用于一线治疗不可切除或转移性肝细胞癌（HCC）患者。祐儿医药儿童多动症新药在中国获批上市1月5日，国家药监局官网公示，祐儿医药和Tris Pharma公司联合申报的5.1类新药盐酸哌甲酯口服缓释干混悬剂已在中国获批上市。根据CDE优先审评公示信息，盐酸哌甲酯属于一种中枢神经系统（CNS）兴奋剂，本次获批适用于治疗注意缺陷多动障碍。亚宝药业暂停一款创新药研发1月2日，亚宝药业发布公告称，宣布公司暂停SY-004的临床研究开发工作。SY-004是亚宝药业在研的1.1类化学药盐酸亚格拉汀胶囊及原料药研发项目，目前处于III期临床前CDE（国家药品监督管理局药品审评中心）沟通交流阶段。据亚宝药业透露，经公司审慎考量SY-004继续开发的投入风险和未来的市场价值，为合理配置公司研发资源，聚焦研发管线中的优势项目，决定暂停SY-004的临床研究开发工作。基于SY-004项目已暂停、未来研发进展存在重大不确定性且相关专利技术未找到潜在可出售对象的实际情况，公司对该项目研发资本化金额5796.6万元全额计提资产减值准备。先声药业GPRC5D/BCMA/CD3三抗IND获NMPA受理1月3日，先声药业注射用SIM0500的临床试验申请获得NMPA受理。SIM0500为一款GPRC5D/BCMA/CD3三抗，中美同步申报。SIM0500在临床前研究中表现出两个靶点的协同效应，比GPRC5D/CD3双抗、BCMA/CD3双抗表现出更好的抗肿瘤活性。君实生物特瑞普利单抗在华获批新适应证1月2日，君实生物宣布，由公司自主研发的抗PD-1单抗药物特瑞普利单抗注射液（拓益）联合化疗围手术期治疗，继之本品单药作为辅助治疗，用于可切除IIIA-IIIB期非小细胞肺癌（NSCLC）的成人患者的新适应证上市申请于近日获得NMPA批准。这是特瑞普利单抗在中国获批的第七项适应证，也是我国首个、全球第二个获批的肺癌围手术期疗法。药明巨诺CAR-T新适应证上市许可申请获受理1月4日，药明巨诺宣布NMPA已受理其靶向CD19的自体嵌合抗原受体T（CAR-T）细胞免疫治疗产品倍诺达（瑞基奥仑赛注射液）用于治疗复发或难治套细胞淋巴瘤（r/r MCL）患者的新适应证上市许可申请（sBLA)。这是药明巨诺针对倍诺达递交的第三项上市许可申请，并有望成为首个在中国批准用于治疗r/r MCL患者的细胞治疗产品。昆药集团碳酸司维拉姆干混悬剂上市申请获受理1月4日，昆药集团发布公告，全资子公司昆明贝克诺顿制药有限公司于近日收到国家药监局下发的《受理通知书》，公司碳酸司维拉姆干混悬剂的药物上市许可申请获国家药监局受理，适用于慢性肾脏病患者的高磷血症控制。目前国内市场仅有碳酸司维拉姆片，原研产品诺维乐于2013年获批上市，用于控制正在接受透析治疗的慢性肾脏病(CKD)成人患者的高磷血症，以及控制血清磷≥1.78 mmol/L但并未进行透析的慢性肾脏病成人患者的高磷血症。智翔金泰赛立奇单抗上市申请获受理近日，智翔金泰发布公告，公司赛立奇单抗注射液放射学阳性中轴型脊柱关节炎(强直性脊柱关节炎)III期临床试验达到了主要疗效终点，向CDE提交了该适应证的新药上市申请并获得受理。此外，赛立奇单抗注射液(GR1501 注射液)中、重度斑块状银屑病适应证新药上市申请已于2023年3月获得受理，为国内企业首家提交新药上市申请的抗IL- 17A单克隆抗体。人福医药氨酚羟考酮片获药品注册证书近日，人福医药发布公告，控股子公司宜昌人福近日收到国家药监局核准签发的氨酚羟考酮片的《药品注册证书》。氨酚羟考酮片适用于严重程度足以需要使用阿片类镇痛剂且缺乏其他替代治疗的中、重度疼痛的治疗。海王生物肿瘤新药在美进入临床近日，海王生物全资子公司海王医药研究院收到FDA签发的书面通知，批准海王医药研究院自主研发、具有自主知识产权的新型肿瘤血管抑制剂NEP018在美国开展I期药物人体临床试验。Orphalan公司罕见病新药曲恩汀在中国获批1月5日，国家药监局官网最新公示，Orphalan公司递交的5.1类新药四盐酸曲恩汀薄膜衣片已正式获批。根据CDE优先审评公示，该产品此次获批适应症为：治疗不耐受D-青霉胺治疗的成人、青少年和≥5岁儿童的Wilson病（威尔逊病，又称肝豆状核变性）。这是一种罕见的慢性遗传病，因肝脏铜转运受损而可能威胁生命，已在中国被纳入《第一批罕见病目录》。资本市场诺华收购信瑞诺医药1月5日，诺华宣布收购信瑞诺医药达成协议，加强在中国肾脏疾病领域的布局。信瑞诺医药是一家专注于肾脏疾病及相关治疗领域的临床阶段中国生物技术公司，成立于2021年，是chinook与数家生命科学投资者共同设立的一家合资公司。诺华于2023年8月收购了Chinook，因而持有该合资公司的部分股权。根据此项协议，诺华将收购信瑞诺医药的其余股份。交易完成后，信瑞诺医药将整体整合入诺华中国。此次收购有望扩大诺华在中国的肾病产品组合，丰富未来产品线，以更好地满足国内肾病患者的治疗需求。罗氏开年三笔BD，总额超40亿美元1月4日，罗氏接连官宣两笔交易。一是与Remix Therapeutics达成合作，将通过Remix的REMaster药物发现平台发现和开发调节RNA加工的小分子疗法。根据协议条款，Remix 将获得 3000 万美元的预付款，并有资格获得高达 1200万美元的近期里程碑付款，以及高达10 亿美元的临床前、临床、商业和销售里程碑付款和分级版税。Remix 将与罗氏一起开展发现和临床前工作，罗氏将负责开发和商业化。二是，与MOMA Therapeutics达成合作，利用MOMA专有知识库（KnowledgeBase）平台，识别参与促进癌症细胞生长和存活的一定数量的新药靶点。根据协议，MOMA将获得6600万美元的预付款现金，并且还有资格获得可能超过20亿美元的发现、开发和商业化里程碑付款以及分级特许权使用费。就在两日前即1月2日，罗氏与宜联生物达成合作，双方将合作开发靶向间质表皮转化因子（c-MET）的下一代抗体偶联药物候选产品YL211（“c-MET ADC”），用于治疗实体瘤。罗氏将向宜联生物支付首付款及近期里程碑付款5000万美元，另外还有近10亿美元的开发、注册和商业化潜在里程碑付款，以及未来基于全球年度销售净额的梯度特许权使用费。文章链接：罗氏开年三笔BD，总额超40亿美元诺和诺德再加码MASH，10亿美元合作Flagship1月4日，诺和诺德宣布，已分别与Flagship Pioneering孵化的Omega Therapeutics和Cellarity公司达成新药研究合作，开发用于肥胖管理的表观遗传药物和针对代谢相关脂肪性肝炎（MASH）的新型疗法。诺和诺德将负责所有研发费用。同时，每家公司的创新产品还有资格获得高达5.32亿美元的首付款和里程碑付款，以及分层版税。文章链接：诺和诺德再加码MASH，10亿美元合作FlagshipTome收购小型DNA编辑技术公司1月2日，可编程基因组整合（PGI）公司Tome Biosciences宣布收购一家私人生物技术公司Replace Therapeutics，该公司正在开发一种能够插入和删除小DNA序列的新型PGI方法。Replace Therapeutics由连续创业者Shakke Halperin博士创立，前一家公司Rewrite Theraputics被Intellia Therapeutics收购，并得到Civilization Ventures的支持。Tome将通过6500万美元前期和近期里程碑合并交易收购Replace Therapeutics，交易总价值高达1.85亿美元包括股票和现金。合并后，Replace Therapeutics将成为Tome Biosciences的全资子公司。澳斯康生物科创板IPO终止1月2日，据上海证券交易所官网，培养基企业澳斯康生物科创板IPO终止。根据此前规划，澳斯康原拟在上交所科创板公开发行股份不超过1,640.61万股，原拟募集资金300,000.00万元，计划用于上海澳斯康偶联药物研发及生产项目、上海澳斯康生物制药CDMO平台项目、补充流动资金。来恩生物与MaxCyte开展全球合作1月5日，来恩生物宣布与 MaxCyte签署一项战略合作协议开展全球合作，利用mRNA技术开发TCR-T疗法治疗实体瘤和病毒相关疾病。这项合作协议使来恩生物能够利用MaxCyte的Flow Electroporation技术和ExPERT™平台加快推进其临床计划和商业应用。根据协议条款，来恩生物将获得MaxCyte的Flow Electroporation技术和ExPERT™平台全球非独家的临床与商业权利，MaxCyte将获得相应的许可费用和相关项目收入。英矽智能小分子抑制剂3月内二度出海1月5日，英矽智能宣布与美纳里尼集团及其全资子公司Stemline Therapeutics达成AI药物对外授权合作，美纳里尼将获得英矽智能自主研发的KAT6小分子抑制剂的全球独家开发和商业化权益。本次合作交易总额逾5亿美元，包括 1200 万美元的首付款，以及后续开发、监管和商业里程碑。此外，英矽智能还有望获得潜在可达两位数的特许权使用费率。该合作是继2023年9月，英矽智能将USP1小分子抑制剂以8000万美元首付款对外授权给纳斯达克上市公司Exelixis后，再次实现自研管线的对外授权。相较于已在中美进入临床1期的USP1项目，本次双方达成合作的KAT6项目所处阶段更为早期。2022年12月英矽智能提名了该项目的临床前候选化合物ISM5043，目前仍在临床前的转化医学研究阶段，包括在PandaOmics的帮助下展开适应证的探索，以及联合用药的开发。安锐生物两款新药授权给Avenzo Therapeutics1月4日，安锐生物与Avenzo Therapeutics达成合作协议，将CDK2抑制剂及另一款临床前新药的大中华区外全球权益授权给后者，Avenzo Therapeutics支付4000万美元预付款，协议总金额超过10亿美元。这并非安锐生物与Avenzo Therapeutics首次合作。就在这次交易的两天前即1月2日，安锐生物刚宣布将EGFR L858R变构抑制剂新药的全球权益授权给阿斯利康，后者支付4000万美元预付款及近期里程碑付款，5亿美元里程碑金额，以及一定比例的销售分成。风险提示沃华医药因违规遭深交所高度关注2023年12月29日，沃华医药公告表示，公司收到由山东证监局出具的警示函。警示函显示，赵丙贤于2023年7月13日被纪检监察机关采取留置措施，但公司直至2023年11 月7日才披露上述事项。按沃华医药公告时间计算，董事长赵丙贤从被留置至留置解除前后仅16天，但实际上，应从2023年7月13日算起，赵丙贤被留置的时间长达133天。深交所对上述事项表示高度关注，对公司及相关当事人涉嫌存在的信息披露违法违规行为，后续深交所将根据中国证监会调查结果，依据《股票上市规则》的相关规定对公司及相关责任人启动纪律处分程序。沃华医药上述行为违反《上市公司信息披露管理办法》相关规定，山东证监局决定对公司及赵丙贤、赵彩霞、曾英姿采取出具警示函的监管措施，并将有关情况记入证券期货市场诚信档案数据库。《合规新观察》认为：根据《证券法》第八十条第二款第（七）项，公司董事长无法履行职责是上市公司应予立即披露的重大事件，上市公司应当立即发布临时公告。如果沃华医药董事长在7月就无法联系、无法正常履职，上市公司很难在四个月后才发现其董事长“失联”，公司存在故意隐瞒该信息、迟至11月份才予披露的违规行为，该行为已涉嫌构成虚假陈述。精彩推荐CM10 | 集采 | 国谈 | 医保动态 | 药审 | 人才 | 薪资 | 榜单 | CAR-T | PD-1 | mRNA | 单抗 | 商业化 | 国际化｜猎药人系列专题启思会 | 声音·责任 | 创百汇 | E药经理人理事会 | 微解药直播 | 大国新药 | 营销硬观点 | 投资人去哪儿 | 分析师看赛道 | 药事每周谈 | 医药界·E药经理人 | 中国医药手册创新100强榜单 | 恒瑞 | 中国生物制药 | 百济 | 石药 | 信达 | 君实 | 复宏汉霖｜翰森 | 康方生物 | 上海医药 | 和黄医药 | 东阳光药 | 荣昌 | 亚盛医药 | 齐鲁制药 | 康宁杰瑞 | 贝达药业 | 微芯生物 | 复星医药｜再鼎医药｜亚虹医药跨国药企50强榜单 | 辉瑞 | 艾伯维 | 诺华 | 强生 | 罗氏 | BMS | 默克 | 赛诺菲 | AZ | GSK | 武田 | 吉利德科学 | 礼来 | 安进 | 诺和诺德 | 拜耳 | 莫德纳 | BI | 晖致 | 再生元

细胞疗法免疫疗法并购一致性评价高管变更

100 项与四盐酸曲恩汀相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	A16AX	-

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
肝豆状核变性	欧盟	Orphalan SA	2017-09-05
肝豆状核变性	冰岛	Orphalan SA	2017-09-05
肝豆状核变性	列支敦士登	Orphalan SA	2017-09-05
肝豆状核变性	挪威	Orphalan SA	2017-09-05

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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


EASL2023	N/A	Menkes综合征	32	Tetrathiomolybdate	鹹壓鑰糧鹽廠壓齋製夢(醖構蓋築艱鬱襯淵餘築) = 構築願鹽網鬱糧鹹窪鹹積廠顧壓膚築醖醖衊鬱 (鬱壓衊構鑰製鹽襯構製 ) 更多	-	2023-06-21
				Trientine	鹹壓鑰糧鹽廠壓齋製夢(醖構蓋築艱鬱襯淵餘築) = 醖淵糧願淵廠淵鹽構顧積廠顧壓膚築醖醖衊鬱 (鬱壓衊構鑰製鹽襯構製 ) 更多
NCT03539952 (EASL2021)	临床3期	肝豆状核变性维持 non-ceruloplasmin copper;(NCC)	53	D-penicillamine	艱蓋顧衊顧範獵構膚繭(蓋鹽範築襯憲齋範齋齋) = 鬱構觸觸願觸構鏇膚餘衊願鹹衊齋鏇廠製醖蓋 (製製鏇醖構鬱顧窪襯壓 )	积极	2021-06-23
				TETA4	艱蓋顧衊顧範獵構膚繭(蓋鹽範築襯憲齋範齋齋) = 願積顧構醖艱鹹選築淵衊願鹹衊齋鏇廠製醖蓋 (製製鏇醖構鬱顧窪襯壓 )
ESC2017	N/A	肥大型心肌病 Copper	20	Trientine dihydrochloride	顧鹹選鬱築範廠鏇鬱夢(製廠窪簾鏇獵範壓繭襯) = 淵鹹鬱襯齋窪廠範簾製鹽廠網醖構築鑰遞鹽積 (衊襯壓願範選製鬱餘構 ) 更多	-	2017-08-28
				trientine	顧鹹選鬱築範廠鏇鬱夢(製廠窪簾鏇獵範壓繭襯) = 積積遞選淵醖構觸網壓鹽廠網醖構築鑰遞鹽積 (衊襯壓願範選製鬱餘構 ) 更多