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-

100 项与四盐酸曲恩汀相关的临床结果

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100 项与四盐酸曲恩汀相关的专利（医药）

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项与四盐酸曲恩汀相关的文献（医药）

Hepatology (Baltimore, Md.)

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

Article

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

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 ; Sandahl, Thomas D ; Czlonkowska, Anna ; 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）

2024-09-02

·Pharma CMC

刚刚，79个新批件，一款罕见病药物获批上市！

刚刚，NMPA发布2024年09月02日药品批准证明文件送达信息，本批次共有79个受理号获批，其中59个为上市申请受理号，获批品种包括：江苏正大清江制药的磷酸奥司他韦干混悬剂；齐鲁制药、昆山龙灯瑞迪制药的达格列净片；平光制药的己酮可可碱注射液；贵州益佰制药的普乐沙福注射液；北京诚济制药的布洛芬混悬液；北京福元医药的丙戊酸钠缓释片（I）等。此外，杰谛医药引进的盐酸曲恩汀胶囊获批上市，用于治疗对不能耐受青霉胺的肝豆状核变性（又称Wilson病）成人及儿童患者。据公开资料显示，盐酸曲恩汀胶囊是一款铜离子络合剂，作用类似青霉胺，可以促使铜通过肾脏排出体外。该药最早由德国默克开发，1985年在美国获批上市，用于治疗威尔逊病，可供不能耐受青霉胺的患者选用。原研药至今未在国内上市。 2023年3月，杰谛医药递交5.2类化药盐酸曲恩汀胶囊的上市申请，后续其上市申请被纳入优先审评。

上市批准优先审批

2024-08-19

·PRNewswire

Behind The Mystery Unveils Treatment in Wilson Disease with Cuviror® by Orphalan

Wilson Disease, a rare, genetic disorder, hampers the body's ability to eliminate copper, leading to serious health issues. Cuvrior® (trientine tetrahydrochloride) is the only FDA-approved treatment in nearly 30 years. FORT LAUDERDALE, Fla., Aug. 19, 2024 /PRNewswire/ -- This special episode of Behind the Mystery features insightful discussions with a dedicated physician, an advocacy leader, and a CEO whose company has pioneered the first FDA approved treatment for Wilson Disease in nearly 30 years. Mandy, diagnosed with Wilson Disease at a young age, shares her journey living with the condition on the show, addressing the challenges faced by patients in managing their treatment regimens and the need for more convenient options. In addition, Hepatologist Dr. Cheung delves into the complexities of Wilson Disease, including its genetic origins, symptoms, and the critical importance of early diagnosis, management, and adherence to treatment. "I'm proud to be part of the 'Behind the Mystery' team, where we use our platform to raise awareness for the rare disease community. Our series underscored the immense challenges faced by patients, as well as the dedication of physicians, the pharmaceutical industry, and advocacy leaders to provide meaningful solutions to the community," said Senior Writer and Producer of Behind the Mystery, Brittany Cocilova. Our latest episode highlights Orphalan's commitment to developing the only FDA-approved therapy for Wilson Disease in nearly 30 years, showcasing the continued efforts to help patients living with and managing their rare disease. Hosts Montel Williams and Olga Villaverde spotlight the Wilson Disease Association's (WDA) efforts to support patients, improve awareness, and facilitate access to developments. Rhonda Rowland, VP of the WDA, discusses the evolution of treatment options and the organization's role in fostering partnerships between patients, physicians, and the pharmaceutical industry. "Orphalan has a tremendous commitment to educating not only the Wilson Disease community and the general public, but also physicians," says Rhonda Rowland, Vice President of Wilson Disease Association. "We've seen a partnership evolve between advocacy and the pharmaceutical industry which enables an open line of communication addressing the unmet needs in our community." Dr. Naseem Amin, CEO of Orphalan, details how Orphalan is addressing unmet needs in the patient community and emphasizes the importance of empathy in the pharmaceutical industry. CUVRIOR®, a treatment marketed by Orphalan, offers a twice-daily dosing and is a non-refrigerated option for long-term maintenance therapy for Wilson Disease. Behind the Mystery - Wilson Disease will air on Lifetime on August 19th and August 27th at 7:30 AM ET/PT and will remain on the website. By sharing these intimate narratives, the series aims to educate the public, inspire empathy, and advocate for better research, treatments, and support systems. INDICATION CUVRIOR is a copper chelator indicated for the treatment of adult patients with stable Wilson Disease who are de-coppered and tolerant to penicillamine. IMPORTANT SAFETY INFORMATION Do not use CUVRIOR if you are allergic to trientine or to any of the ingredients in CUVRIOR. Your Wilson's Disease symptoms could get worse when you start treatment. This could happen because too much copper is removed from the body in a short period of time. Your doctor may need to reduce your dose or stop CUVRIOR treatment. Copper deficiency may develop following treatment with CUVRIOR. Your doctor will do tests to monitor your urine and blood for copper. Iron deficiency may develop while taking CUVRIOR. If this happens, your doctor may tell you to take iron supplements for a limited time. Allergic reactions, such as a rash, have been reported with trientine, the active ingredient in CUVRIOR. If a rash or other allergic reaction occurs, stop taking CUVRIOR and get emergency medical help. The most common side effects are pain in the abdomen, change in bowel habits, rash, hair loss (alopecia), and mood swings. Take CUVRIOR at least 1 hour apart from any other oral medicine. Tell your doctor about all the medicines you're taking, including over-the-counter medicines, vitamins, and herbal supplements. Avoid taking supplements when taking CUVRIOR. Taking CUVRIOR with mineral supplements (e.g., iron, zinc, calcium, magnesium) can reduce the effectiveness of CUVRIOR. If iron supplementation is necessary, take CUVRIOR at least 2 hours before or 2 hours after taking iron; for other mineral supplements (e.g., zinc, calcium, magnesium), take CUVRIOR at least 1 hour before or 2 hours after. Do not start or stop any medicines while taking CUVRIOR without talking to your doctor. These are not all the possible side effects of CUVRIOR. You are encouraged to report negative side effects of prescription drugs. Contact Orphalan at 1-800-961-8320 or [email protected] or FDA at 1-800-FDA-1088 or medwatch. Please see full Prescribing Information at: About Behind the Mystery: Behind the Mystery™ is the first and only television series dedicated to raising awareness about rare and genetic diseases through powerful patient storytelling. Each episode delves into the personal journeys of individuals and families affected by these conditions, highlighting their struggles, triumphs, and daily realities. By sharing these intimate narratives, the series aims to educate the public, inspire empathy, and advocate for better research, treatments, and support systems. Behind the Mystery not only sheds light on the medical aspects of rare diseases but also celebrates the resilience and strength of the human spirit. Join us weekday mornings on Lifetime®. About Orphalan Orphalan is an international orphan drug development and commercialization company headquartered in Paris. Founded in 2011, the company develops innovative therapies for people living with rare and debilitating diseases. Our trientine tetrahydrochloride product for the treatment of Wilson disease is approved and available in more than 20 countries, branded as CUPRIOR® in EU, the UK, Saudi Arabia, Switzerland, Columbia and China, and as CUVRIOR® in the United States. For more information visit and follow us on LinkedIn. SOURCE Behind The Mystery

孤儿药上市批准

2024-07-13

·E药经理人

我，黑龙江药企市值一哥，距离中药TOP10还差50亿

葵花药业，一家稳健赚钱、分红大方的企业，却“输”在了对未来的预期上。资深分析师：石若萧图文编辑：苏叶这两年，随着各种因素集中爆发，A股有三分之二的医药公司开启了漫长的下跌之路。但中药板块的表现却大大好于平均水平，尤其OTC类药品，因为不受医保谈判、国家集采等政策的影响，定价自由，且大多走院外市场，更是迎来了飞速发展。中药OTC企业的代表，如华润三九、东阿阿胶、太极集团等，2021年至今，股价几乎一直保持着上涨趋势。从中药OTC板块进一步拆分下去，每家企业的个体增长逻辑又有不同。东阿阿胶牢牢把握住了细分品类第一的位置；华润三九靠外延并购持续增长，擅长用自身庞大的商业渠道体系为子品牌赋能；太极集团手握藿香正气水这样的超级大单品，旗下也有商业板块赋能销售，许多方面还能与国药互通有无…… 这一众“庞然大物”中，葵花药业是个颇为特殊的存在：2023年，它的营收规模只有太极集团的三分之一，归母净利润（11.19亿元）却比后者显著高出不少。从这一角度看，葵花的经营效率远高于太极，但论市值（发稿日141亿）却较太极（156亿）更低。另一方面，手握“葵花”、“小葵花”两大知名品牌（年报中披露机构评估两品牌价值近200亿元），护城河也不低。加上分红大方的口碑——自2014年上市后，葵花药业累计现金分红金额超28亿元，已超公司上市募集资金总额的2倍。但现实是，作为黑龙江药企市值一哥，葵花的股价一直无法突破，距离中药上市公司的市值TOP10稳定在50亿左右。这些局面，到底是如何造成的？是被高估还是低估了？带着问题，CM10医药研究中心将从行业稀缺值、财务健康度、业务健康度、综合建议，来一一回答。儿科“头号玩家” 连续几年，几乎每一年的年报中，葵花药业都会提到这样一句话：儿童药战略是公司的第一核心战略。儿童药是个黄金赛道，具有空间大，竞争少的特点。第七次全国人口普查显示，我国0-14岁人口占总人口比例达17.95%。另研究显示，2015-2020年，我国儿童用药市场规模从591亿元增长至948亿元。然而我国3500多种药品制剂中，儿童专用剂型仅占1.7%，专门生产儿童药的企业只有30-40家，出现了明显的供需错配。葵花药业正填补了这一空白，旗下“小葵花”品牌主抓儿童药，产品覆盖儿童的呼吸系统、消化系统、补益系统、健康领域几类。主打明星产品包括小儿肺热咳喘口服液/颗粒、小儿柴桂退热颗粒等。可以看到，“小葵花”的产品线基本都是中药OTC产品，且聚焦在呼吸道上。儿科、中药、OTC、呼吸道，一路细分下来，葵花的直接竞争对手其实并不多，也就葫芦娃、济川药业、健民集团等这么几家。葫芦娃和健民集团虽然都是老一派儿童用药领军企业，但前者无论市值、品牌认知和产品销量都显著低于葵花；后者儿科类产品有健脾生血颗粒、小儿宝泰康颗粒、小儿宣肺止咳颗粒等，2023年儿科产品销量为3123.51万盒，同比下降5.01%，颓势显现。济川药业是葵花药业最强势的竞争对手，去年第四季度呼吸系统疾病高发，包括小儿豉翘清热颗粒在内的主力产品大卖，让济川药业2023年净利润实现30%的同比增速；而核心产品蒲地蓝消炎口服液自2003年上市以来累计销售额已经突破百亿元，连续多年位居清热解毒类口服中成药第一名，尽管遭遇了多地医保清退，但对业绩似乎并未造成明显影响。单品硬碰硬，“小葵花”同济川药业的蒲地蓝消炎口服液、小儿豉翘清热颗粒仍有一定差距，对此，葵花的战略是增加产品布局，构筑全套体系，通过品牌和产品组合整体出击。整体营销理念加持下，儿童药领域“小葵花”的认知度，要远高于某个单药的认知度。此外，“葵花”成人药产品覆盖消化系统、呼吸感冒系统、风湿骨病系统、心脑血管系统、妇科、补益及健康领域，其中护肝片2023年发货金额首次突破10亿规模。儿童药领域建立起了强大的品牌心智和产品组合，成人药领域又有护肝片这样一个10亿级别大单品。放眼望去，葵花几乎没有对手，难怪这几年一直像印钞机一样赚钱和分红。收入增长不明显靠内部优化提升利润受到疫情等因素影响，2019-2023年这段时间，葵花药业的收入增长并不算明显—— 2019年营业总收入43.7亿，2023年营业收入57.00亿，年均复合增长率约与整个中药OTC板块增速水平相当。但值得注意的是，同一期间，该公司的归母净利润几近翻倍，从5.83亿元到11.19亿元，远超过了收入的增长速度。净利润增速高于收入增速，一定程度上说明公司的经营结构在优化，费用控制合理，经营效率得到了提升。拆解年报数据来看，公司的毛利率2019年为58.66%，2023年为56.41%，基本持平。费用则主要分为四项：研发费用、管理费用、财务费用和销售费用。研发一向不是中药OTC企业的强项，葵花药业亦不例外。2019年研发费用为1.18亿，2023年为1.29亿，占营收比2%上下，几乎持平。管理费用也在正常范围内。有趣的是财务费用和销售费用。由于葵花的现金流很充沛，手握巨额银行存款，其中一部分被用来对外贷款和购买理财，利息收入冲抵了财务费用，导致该项一直为负，并且从2019年的-161万扩大到了2023年的-3196万，手头还握有22.8亿的银行存款和13亿理财产品。来源：葵花药业2023年年报销售费用方面，葵花药业的顶峰在2018年，为14.47亿；到了2019年忽然显著下降11.77%到12.76亿，到2023年缓慢回升到13.66亿，五年时间里几乎持平。然而拆细了看，发生了一轮明显的结构优化：2018年销售人员数量为1792，2019年下降到1461，到2023年又回升到1681人，职工薪酬翻了一倍多，广告费用略有增长，但同时完全去掉了“运输及车辆使用费”和“营销上架费”两个项目。来源：葵花药业2019年年报来源：葵花药业2023年年报乍一看，这些变动有点令人摸不着头脑，但从客户集中度上可以推测出端倪：葵花药业的客户集中度在进一步提高，公司前5大客户销售金额自2019年的41.30%提升至2023年的51.85%，占比过半；第一大客户销售额占比由2019年的21.73%提升至31.76%，年销售额从9.5亿元几乎翻倍至18亿元。来源：葵花药业2019年年报来源：葵花药业2023年年报上市之初，葵花药业招股书曾披露过其第一大客户是九州通，2023年年报中虽然没披露相关信息，但按占比分析，也只可能是某家巨头。普通药企面对流通巨头时，议价权较低，容易被压款。但葵花药业2023年应收帐款数量却很少，期初账面余额1.64亿，期末账面余额下降到7600余万。且管理层披露其商业模式为预收款再发货，显示出其有一定的谈判能力。将上述信息整合后，一个合理推测是，经过多年的组合营销，葵花药业已经建立起了强大的品牌心智，产品有竞争力，谈判议价有底气，于是基于效率考虑优化掉了一部分销售团队，将剩余团队精英化，把“苦活累活”都外包出去给了流通公司。这样一来，销售团队就不必随着销售额的扩大而扩张了，净利润率自然也就上去了。估值空间：在哪？整体看下来，葵花药业是一家基本面非常优秀，财务表现极其稳健的公司。产品强势、不愁销量，又大搞内部改革，实现了降本增效。但居安思危，“容易的钱”也不能一直赚，葵花药业看似稳健的经营模式里，其实也蕴含着风险。早年传播媒介集中，光靠电视台轰炸就能将“小葵花妈妈课堂开课啦！”等广告语烙进消费者心智。如今传播媒介分散，“广告拉、处方带、OTC推、游击队抢”的老战术未必依然有效。倘若未来品牌认知度没能与时俱进，自身又缺乏渠道布局，那么在流通公司一侧的议价权也必将降低。葵花药业的管理层也逐渐意识到了这一点，其于年报中提及，未来将在营销方面构建黄金大单品打造方法论、落地营销推广新逻辑。面对近年来快速发展的数字化、智能化、AI时代，公司将结合自身优势，更新认识论与方法论，构建新质成长力，落地营销推广新逻辑，高位驱动，引领传统医药产业模式升级。不过这些都是比较空泛的表述，没有具体说明该怎么做，接下来的表现还有待观察。此外，二级市场上，投资者看的都是未来预期，而医药公司的预期又与产品强挂钩，光靠营销和内部优化经营效率远远不够。但这恰恰是葵花药业的薄弱之处，赚的钱没有用来进一步搞研发，而是大手笔分红或买理财赚利息，使公司在二级市场上缺乏想象力，进而导致股价和市值一直上不去。这个问题何解？葵花药业给出的答案是“扩张”，在将儿童药作为第一核心战略的基础上，往其他方面过渡。去年底，公司答投资者问时表示，正在不断完善自身产品布局，糖尿病、肾病领域也是公司成人药关注的领域之一，目前这类产品尚处在研阶段。葵花药业2023年年报中也提及，未来几年，随着公司的布洛芬混悬液、布洛芬混悬滴剂、磷酸奥司他韦干混悬剂以及其他在研品种有望获得生产批件并投放市场，将为公司规模扩大注入新的动能。同时，公司将进一步研发及引入符合公司战略和匹配组织能力的产品，持续为公司成长注入新生力量。另外，公司将继续实施“实业+资本”双轮驱动，从全球视野、行业前沿、适度超前的维度，以结果为导向，灵活地运用资本手段，提升新产品、新领域拓展与获取能力，有效提升传统并购后整合能力，实现外延式增长。看上去很美。不过，发力仿制药，建企业投资（CVC），靠并购和BD拉动增长，这是华润三九、济川药业等大企业走过的路径，却并不一定适合葵花药业。首先，上述产品都属于仿制药，许多药企都有布局，葵花即使进入也没有竞争力，反而会稀释好不容易积累起来的品牌用户心智。其次，由于本身欠缺渠道优势和政策优势，贸然在成人药领域搞外延并购，或难以整合自身优势资源。对此，CM10医药研究中心的建议是：不要去卷成人药，无论自研还是并购，扎根儿童药领域进一步做深做强。早在最初，葵花药业就是靠着兼并扩大规模的，11年收购了11家药厂，总花费不到20亿元。2021年，葵花药业以MAH模式拿下6个儿童用药品种，并通过BD获得印度瑞迪制药两款儿童罕见病用药己烯酸口服溶液用散、曲恩汀胶囊的国内代理权。2022年，葵花药业又宣布拟出资5400万元投资设立北京葵花医药研究有限责任公司，致力于国内外优质儿童制剂技术引入、儿童仿制制剂研发、公司儿童用药领域现有品种和技术的提档升级。有人才，有经验，完全可以照着这个路子一直走下去。如果说过去二十年，葵花药业的任务主要是靠打造产品、建立品牌。那么现在到了稳定期，需要的不是乱铺摊子，而是集中资源、攻坚克难，不断并购儿童药领域优势产品，和既有资源进行嫁接，把更多的时间精力资源投入到产品研究和临床循证观察上，真正意义上把自己变成儿科创新药领域的“一把手”。 “ 任何伟大的变革都是痛苦的。我们已经见证了，诸多仿制药企走向创新药企历经的黑暗与迷茫岁月。我们已经看见了，一些蜕变，和新价值的诞生。CM10医药研究中心致力于上市公司的价值发现、挖掘与诊断。” 如感兴趣请进入资本群交流微信：MJesie 免责声明：本文章是基于上市公司的公众公司属性、以上市公司公开披露的信息（包括但不限于临时公告、定期报告和官方互动平台等）为核心依据的独立第三方研究；CM10医药研究中心力求报告(文章)所载内容及观点客观公正，但不保证其准确性、完整性、及时性等：本报告(文章)中的信息或所表述的意见不构成任何投资建议，CM10医药研究中心不对因使用本报告（文章）所采取的任何行动承担任何责任。一审| 黄佳二审| 李芳晨三审| 李静芝回复“逆商”，了解电子期刊详情精彩推荐 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 | 出海启思会 | 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

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	鏇鏇齋願鏇繭壓築觸夢(夢鹽艱糧餘網艱願齋餘) = 鏇鏇壓廠齋願網鹽憲夢構繭夢網繭鬱艱積夢願 (淵觸淵鹹憲範鹹衊艱鹹 ) 更多	-	2023-06-21
				Trientine	鏇鏇齋願鏇繭壓築觸夢(夢鹽艱糧餘網艱願齋餘) = 窪憲壓蓋製範鬱艱鑰壓構繭夢網繭鬱艱積夢願 (淵觸淵鹹憲範鹹衊艱鹹 ) 更多
NCT03539952 (EASL2021)	临床3期	肝豆状核变性维持 non-ceruloplasmin copper;(NCC)	53	D-penicillamine	憲膚憲鏇獵構鹹壓獵糧(窪夢憲廠餘構築範鏇鬱) = 選選鑰鑰願鹽觸餘鏇餘醖糧憲衊顧壓窪衊築積 (衊艱鏇襯觸簾顧艱鬱網 )	积极	2021-06-23
				TETA4	憲膚憲鏇獵構鹹壓獵糧(窪夢憲廠餘構築範鏇鬱) = 窪壓壓範艱膚醖鏇鏇鹹醖糧憲衊顧壓窪衊築積 (衊艱鏇襯觸簾顧艱鬱網 )
ESC2017	N/A	肥大型心肌病 Copper	20	Trientine dihydrochloride	鬱範獵積遞鑰鹽衊鬱顧(築餘齋襯範觸膚顧窪範) = 簾醖製鏇蓋積醖鏇膚壓蓋壓膚齋淵鹹網簾醖襯 (窪觸觸範夢淵鬱鹽蓋窪 ) 更多	-	2017-08-28
				trientine	鬱範獵積遞鑰鹽衊鬱顧(築餘齋襯範觸膚顧窪範) = 獵衊鏇願範繭糧鬱膚鏇蓋壓膚齋淵鹹網簾醖襯 (窪觸觸範夢淵鬱鹽蓋窪 ) 更多