Open label, Multicenter, Prospective Study to Characterize the Pharmacokinetics and Pharmacodynamics of Cufence (Trientine Dihydrochloride) and to Investigate the Efficacy and Safety in Wilson’s Disease Patients - TR-004 UNITED Study

Start Date08 Oct 2021

Sponsor / Collaborator-

CTR20211406 / Active, not recruitingPhase 2

一项在心力衰竭和射血分数降低患者中评价 INL1（Trientine）效果的随机化、双盲、安慰剂对照研究

[Translation] A randomized, double-blind, placebo-controlled study evaluating the effects of INL1 (Trientine) in patients with heart failure and reduced ejection fraction

目的：主要目的：评价12周时INL1（盐酸曲恩汀）与安慰剂相比在NYHA 心功能分级Ⅱ～Ⅲ级伴左心室射血分数降低（LVEF<40%）的心力衰竭患者中的疗效。次要目的：评价INL1（盐酸曲恩汀）与安慰剂相比在心力衰竭患者中的安全性和耐受性。描述12周治疗期间INL1（盐酸曲恩汀）的药代动力学（PK）特征

[Translation]

Objective: Primary objective: To evaluate the efficacy of INL1 (trientine hydrochloride) compared with placebo in patients with heart failure of NYHA class II-III with reduced left ventricular ejection fraction (LVEF<40%) at 12 weeks. Secondary objective: To evaluate the safety and tolerability of INL1 (trientine hydrochloride) compared with placebo in patients with heart failure. To describe the pharmacokinetic (PK) characteristics of INL1 (trientine hydrochloride) during 12 weeks of treatment

Start Date01 Jul 2021

Sponsor / Collaborator

Frontage Laboratories, Inc.

[+2]

NCT04706429 / Active, not recruitingPhase 2IIT

A Randomised, Double-blind, Placebo-controlled, Phase 2 Evaluation of the Efficacy and Mechanism of Trientine in Patients With Hypertrophic Cardiomyopathy

This research study has been designed to test whether a drug called trientine dihydrochloride (also called Cufence) reduces heart muscle thickening, improves exercise capacity, improves heart function and reduces abnormal heart rhythms in patients with hypertrophic cardiomyopathy (HCM). The study is also assessing how trientine works in HCM. Participants will be prescribed either trientine or placebo, for a period of 12 months.

Start Date01 Dec 2020

Sponsor / Collaborator

Manchester University NHS Foundation Trust

[+5]

100 Clinical Results associated with Trientine Hydrochloride

100 Translational Medicine associated with Trientine Hydrochloride

100 Patents (Medical) associated with Trientine Hydrochloride

461

Literatures (Medical) associated with Trientine Hydrochloride

01 Dec 2024·Regenerative Therapy

Research progress in stem cell therapy for Wilson disease

Review

Author: Gao, Ce ; Xiong, Xianlang ; Liu, Aihui ; Meng, Xiangying ; Sun, Yi ; Gong, Xin

Wilson disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive disorder characterized by disorganized copper metabolism caused by mutations in the ATP7B gene. Currently, the main treatment options for WD involve medications such as d-penicillamine, trientine hydrochloride, zinc acetate, and liver transplantation. However, there are challenges that encompass issues of poor compliance, adverse effects, and limited availability of liver sources that persist. Stem cell therapy for WD is currently a promising area of research. Due to the advancement in stem cell directed differentiation technology in vitro and the availability of sufficient stem cell donors, it is expected to be a potential treatment option for the permanent correction of abnormal copper metabolism. This article discusses the research progress of stem cell therapy for WD from various sources, as well as the challenges and future prospects of the clinical application of stem cell therapy for WD.

01 Nov 2024·JIMD Reports

Clinical experience on switching trientine tetrahydrochloride to trientine dihydrochloride in Wilson disease patients

Article

Author: Merle, Uta ; Schmitt, Timo ; Schall, Nicolas ; Langel, Andrea ; Poujois, Aurélia ; Weiss, Karl Heinz ; Leidner, Viola Yuriko ; Mohr, Isabelle ; Langel, Jessica ; Weber, Christophe

AbstractThis study evaluates the effectiveness and safety of trientine dihydrochloride (TETA 2‐HCl) in patients with Wilson disease (WD) following a switch from trientine tetrahydrochloride (TETA 4‐HCl). A total of 30 WD patients with stable copper metabolism were identified for treatment with TETA 2‐HCl (Cufence™) after prior use of TETA 4‐HCl (Cuprior™). Biochemical markers including urinary copper, non‐ceruloplasmin bound copper (NCC) and liver function were analyzed at baseline and followed up over 12 months. Safety was assessed based on reported adverse events (AEs). Urinary copper levels and NCC remained stable across all follow‐ups, indicating adequate copper metabolism control. Reported AEs during TETA 2‐HCl treatment were mostly gastrointestinal discomfort (n = 6). In two patients, progressive elevation of transaminases occurred (despite stable copper metabolism). AEs led to discontinuation of treatment in five cases. Median baseline dose per day was 10.2 mg TETA 4‐HCl/kg bodyweight, whereas median baseline dose after therapeutic switch to TETA 2‐HCl was 12.8 mg/kg bodyweight. Median daily dose at 12 months did not differ significantly from TETA 2‐HCl dose at switching timepoint, with stable biochemical markers and markers of copper metabolism in most (25/30) of the patients. Transitioning from TETA 4‐HCl to TETA 2‐HCl maintained stable copper parameters and liver function in most of analyzed patients. TETA 2‐HCl treatment was generally well tolerated, suggesting that switching medications is safe and effective. In our real‐life cohort, adjustment factor of ~1.25× for the switch of TETA 4‐HCl to TETA 2‐HCl resulted in adequate copper metabolism control.

01 Oct 2024·Drug Research

The Effect of Trientine on AlCl3-Induced Cognitive Dysfunction and Biochemical Changes in the Hippocampus of Rats

Article

Author: Amani, Mohammad ; Mostafalou, Sara ; Mousavi-Nasab, Kian

AbstractCognitive impairments affect millions of people worldwide with an increasing prevalence. Research on their etiology and treatment is developing, nevertheless significant gaps remain. Trientine (TETA), as a copper chelator, has been shown to have beneficial effects in different human chronic diseases such as diabetic cardiomyopathy and neuropathy. Here, we examined the impact of TETA on AlCl3-induced neurocognitive dysfunctions and molecular changes in the hippocampus of rats.Thirty-six male Wistar rats (weighing 200–250 g) were randomly divided into four groups including control, TETA (100 mg/kg/day), AlCl3 (100 mg/kg/day), and AlCl3 (100 mg/kg/day)+TETA (100 mg/kg/day), and received chemicals by gavage for 30 days. At the end of the treatment, the open field maze, elevated plus maze, novel object recognition memory test, and shuttle box test were done. Then after, brain-derived neurotrophic factor (BDNF), glycogen synthase kinase-3 β (GSK-3β), acetylcholinesterase activity, oxidative stress markers, and inflammatory mediators were measured in the hippocampus.AlCl3 increased anxiety-like behaviors and impaired recognition and short-term memory. TETA was able to improve AlCl3-induced anxiety-like behaviors and short-term memory dysfunction. In the AlCl3-treated group, there was a significant increase in GSK-3β, oxidative stress, pro-inflammatory and pro-apoptotic markers, and decreased BDNF in the hippocampus. Co-administration of TETA was able to decrease lipid peroxidation, inflammation, GSK-3β, and acetylcholinesterase activity, and increase BDNF in the hippocampus compared with AlCl3-treated rats.It can be concluded that TETA was able to improve neurobehavioral and neurocognitive functions by alleviating oxidative stress, inflammation, and pro-apoptotic pathways leading to the normalization of BDNF and GSK-3β.

News (Medical) associated with Trientine Hydrochloride

28 Oct 2024

·www.globenewswire.com

Monopar Announces Agreement with Alexion, AstraZeneca Rare Disease For Late-Stage Wilson Disease Drug Candidate

Oct. 24, 2024 -- Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biotechnology company focused on developing innovative treatments for patients with unmet medical needs, today announced that it has entered into an agreement with Alexion, AstraZeneca Rare Disease for an exclusive worldwide license to ALXN-1840 (bis-choline tetrathiomolybdate), a drug candidate for Wilson disease that Alexion has progressed through a Phase 3 clinical trial that met its primary endpoint. Monopar will be responsible for all future global development and commercialization activities. Chandler D. Robinson, MD, Co-Founder and Chief Executive Officer of Monopar previously researched tetrathiomolybdate at the laboratory bench, published his results in Science, and helped launch a company around what became known as ALXN-1840. The focus was on Wilson disease. Dr. Robinson came to know the Wilson disease community well through his efforts. At the Wilson Disease Association’s request, he delivered the keynote address at their 2013 Annual Conference celebrating their 30th anniversary, sharing his experience helping advance ALXN-1840 from the laboratory bench to patients. In 2023, Alexion terminated the ALXN-1840 program in Wilson disease based on review of results from Phase II mechanistic trials and discussions with regulatory authorities. Chris Starr, PhD, Co-Founder and Executive Chair of Monopar said, “Upon the 2023 announcement, Chandler, due to his long history with the program and the continued high level of unmet medical need, was contacted by Wilson disease patients, executives and board members of the Wilson Disease Association, as well as physicians regarding the potential for Monopar to obtain rights to ALXN-1840. Due in no small measure to the testimonials Chandler received from clinical trial patients who reported benefit while on the drug for years, we decided that this was an opportunity Monopar needed to pursue, and it fits well with my rare disease drug development and commercialization background as well as Chandler’s background.” Dr. Starr also previously co-founded the orphan drug companies BioMarin and Raptor Pharma (acquired by Horizon Pharma, now a part of Amgen). Dr. Robinson commented, “Alexion has generated a substantial clinical data package on ALXN-1840, including a completed Pivotal Phase 3 clinical trial. The medical data gathered from Alexion’s clinical trials furthers our understanding of Wilson disease and stands to benefit this community.” Under the terms of the license agreement, Monopar will pay Alexion an upfront in the form of a cash payment and equity in Monopar. Future payments are based on tiered royalties on net sales and pre-determined regulatory and sales milestones. “We are excited to have Alexion and AstraZeneca as partners of Monopar as, in addition to Alexion’s work in Wilson disease, AstraZeneca maintains a significant presence in the radiopharma field, in which Monopar is committed to continue growing as Monopar recently announced positive human clinical data with our novel radiopharma program (link),” stated Andrew Cittadine, Chief Operating Officer of Monopar. Wilson disease is a rare and progressive genetic condition in which the body’s pathway for removing excess copper is compromised. 1 It affects one in 30,000 live births in the US.1 Over time this results in the build-up of toxic copper levels in the liver, brain, and other organs, leading to damage that greatly impacts a patient’s life. 1 Patients can develop a wide range of symptoms, including liver disease and/or psychiatric or neurological symptoms, such as personality changes, tremors and difficulty walking, swallowing or talking. 1 In some cases, the damage and loss of function may be irreversible. 1,2,3 ALXN-1840 (bis-choline tetrathiomolybdate) is an investigational once-daily, oral medicine in development for the treatment of Wilson disease. This novel molecule is designed to selectively and tightly bind and remove copper from the body’s tissues and blood. ALXN-1840 has been granted Orphan Drug Designation in the United States and orphan designation in the European Union for Wilson disease. The FoCus trial was a pivotal Phase 3, randomized, rater-blinded, multi-center clinical trial designed to evaluate the efficacy and safety of ALXN-1840 versus standard-of-care (SoC) in patients with Wilson disease aged 12 years and older. The primary endpoint assessed copper mobilization over 48 weeks, defined as daily mean AUEC (Area Under the Effect Curve) for dNCC (directly measured non-ceruloplasmin-bound copper). In the trial, 214 patients were enrolled in one of two cohorts on a 3:1 basis (treatment-experienced:treatment-naïve). Each cohort was then randomized 2:1 (ALXN1840:SoC). The first cohort enrolled 161 patients who received SoC (chelation therapy with penicillamine or trientine, zinc therapy or a combination of both chelation and zinc therapy) for more than 28 days and the second cohort enrolled 53 patients who were treatment-naïve or had received SoC for 28 days or less. The FoCus trial met its primary endpoint demonstrating three-times greater copper mobilization from tissues compared to the SoC arm (Least Square Mean Difference [LSM Diff] 2.18 µmol/L; p Monopar Therapeutics is a clinical-stage biotechnology company with late-stage ALXN-1840 for Wilson disease, and radiopharma programs including Phase 1-stage MNPR-101-Zr for imaging advanced cancers, and Phase 1a-stage MNPR-101-Lu and late preclinical-stage MNPR-101-Ac225 for the treatment of advanced cancers. For more information, visit: www.monopartx.com. References: 1. Patil, M., et al. (2013) J Clin Exp Hepatol, 3, 321-336. 2. Roberts, E.A., Schilsky, M.L. American Association for the Study of Liver D. (2008). Diagnosis and treatment of Wilson disease: An update. Hepatology, 47(6), 2089-2111. 3. European Association for the Study of the Liver. (2012). EASL clinical practice guidelines: Wilson’s disease. J Hepatol, 56(3), 671-685. The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultLicense out/inOrphan Drug

19 Aug 2024

·www.prnewswire.com

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

Orphan DrugDrug Approval

18 Jan 2024

·www.globenewswire.com

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

Drug ApprovalOrphan Drug

100 Deals associated with Trientine Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D00736	Trientine Hydrochloride	A16AX	DB06824

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatolenticular Degeneration	CA	Marcan Pharmaceuticals, Inc.	-

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatolenticular Degeneration	NDA/BLA	CN	Jiedi Pharmaceutical Technology (Shanghai) Co., Ltd.	11 Mar 2023
Cardiomyopathy, Hypertrophic	Phase 2	GB	Univar Solutions, Inc.	01 Dec 2020
Heart Failure	Phase 2	US	INNOLIFE CO., LTD.	30 Dec 2019
Heart Failure	Phase 2	US	CopMed，Inc.	30 Dec 2019
Heart Failure	Phase 2	US	Frontage Laboratories, Inc.	30 Dec 2019
Myocardial Infarction	Phase 2	CN	INNOLIFE CO., LTD.	-
Myocardial Ischemia	Phase 2	CN	INNOLIFE CO., LTD.	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02426905 (EASL2019)	Phase 4	Hepatolenticular Degeneration	52	Trientine dihydrochloride	acoehefsbe(jqhdsadzst) = 8 (15.4%) patients reported serious TEAEs inujjbttsa (nmrijxfqbv ) View more	-	12 Apr 2019
ESC2017	Not Applicable	Cardiomyopathy, Hypertrophic Copper	20	Trientine dihydrochloride	xuuyjjxyjo(pvtwnneeia) = auygrkuuwe ogklmllltv (lannbkmfnr ) View more	-	28 Aug 2017
ESC2017	Not Applicable	Cardiomyopathy, Hypertrophic Copper	20	trientine	xuuyjjxyjo(pvtwnneeia) = llgwcggubf ogklmllltv (lannbkmfnr ) View more	-	28 Aug 2017

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