Treatment of Wilson's Disease for Patients in the United Kingdom

Updated May 2023 by Rupert Purchase

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Introduction

Copper is a small but essential part of our daily diet. In patients with Wilson's disease, the route of excretion of dietary copper is impaired and this results in an overload of copper in the body. The signs and symptoms of Wilson's disease are the consequence of this copper overload affecting various organs such as the liver and the brain. Wilson's disease can be treated by reducing the copper overload with the use of appropriate medication.

Drugs approved in the UK for Wilson's disease and how they work – May 2023

Currently, four drugs are approved for use in the UK for treating Wilson’s disease: D-penicillamine, trientine in the form of trientine dihydrochloride or trientine tetrahydrochloride, and zinc acetate dihydrate. All four drugs are taken orally. D-Penicillamine and the two trientine formulations are chelating agents and they can remove copper from the body via urinary excretion. Zinc acetate dihydrate has a different mode of action. It essentially limits the intestinal absorption of dietary copper, which leads to an overall decrease in copper overload in the body.

Taking the medication regularly

For patients newly diagnosed with Wilson's disease, the initial choice of one of these four drugs and the number of capsules or tablets to be taken each day will be determined by their consultant. In order to reduce copper overload, it is very important for patients to take their prescribed medication regularly, and at recommended times during the day. Treatment is lifelong. Taking the medication on an empty stomach will enhance the amount of these drugs which is absorbed by the body. Patients will be given advice about the best way to take their medication between meals.

Brand names

Trientine and penicillamine are the generic (INN) names for these two drugs, while zinc acetate dihydrate is the accepted chemical name for this substance. But in addition, brand names are also used to identify penicillamine, the two trientine formulations and zinc acetate. In the UK, one of the many brand names for penicillamine is Distamine and for trientine dihydrochloride (manufactured for Univar Solutions, Rotterdam) it is Cufence. For trientine tetrahydrochloride (manufactured for Orphalan UK, St Albans) the brand name Cuprior has been adopted in the UK. (In the USA, where FDA approval for trientine tetrahydrochloride has been granted, the brand name is Cuvrior). Zinc acetate has the brand name Wilzin and is marketed in the UK by Recordati Rare Diseases UK, Bracknell.

Package leaflets

Brand names are used to identify the drugs used to treat Wilson's disease in Package leaflets: information for the patient. These leaflets are always included with a prescribed medicine and provide much useful information such as recommended doses, possible adverse effects, dietary advice and how to store the medication. Here are some weblinks to package leaflets for the drugs currently approved to treat Wilson’s disease patients in the UK:

Penicillamine: 
https://www.medicines.org.uk/emc/files/pil.2712.pdf
(Viatris, formerly Mylan);

Pencillamine 125mg & 250mg Tabs PIL (V5P1) (kentpharma.co.uk)
https://medicines.kentpharma.co.uk/wp-content/uploads/2022/12/uk-mockup-pl0012-21192-21147.pdf
(Kent Pharmaceuticals)

Trientine dihydrochloride (Cufence - see notes below) (Univar): pil.11808.pdf
https://beta.medicines.org.uk/emc/files/pil.11808.pdf
(medicines.org.uk)

Trientine dihydrochloride (available from Tillomed Laboratories Ltd. UK): https://www.medicines.org.uk/emc/files/pil.11626.pdf

Trientine tetrahydrochloride (Cuprior) (Orphalan):
https://www.cuprior.com/?location=United%20Kingdom
Home - Cuprior

Zinc acetate (Wilzin) (Recordati): Wilzin, INN-zinc acetate dihydrate
https://www.medicines.org.uk/emc/files/pil.6245.pdf?view=pil
(medicines.org.uk)

Liver transplantation

Liver transplantation is needed for Wilson's disease patients with acute liver failure at initial presentation or end-stage liver failure as a result of discontinued or unsuccessful drug therapy. The conundrums and outcomes of liver transplants in Wilson's disease have been summarised (Michelle Camarata et al, ‘General considerations and the need for liver transplantation'. In, Wilson Disease: Pathogenesis. Molecular Mechanisms, Diagnosis, Treatment and Monitoring, edited by Karl Heinz Weiss and Michael Schilsky, Academic Press, London, 2019, chapter 15, pp 173-182; https://www.sciencedirect.com/science/article/pii/B9780128110775000153 

Future treatments for Wilson's disease

Four promising treatments for Wilson’s disease are listed below.

Gene therapy and antisense technology both offer the prospect of a cure for the genetic defect responsible for the copper overload in patients with Wilson’s disease, thus removing the need for drug therapy. The chelating agent DPM-1001 decreased copper levels and ameliorated deficits in a model of Wilson's disease. Clinical trials of another promising drug for Wilson’s disease, the copper-binding agent bis(choline) tetrathiomolybdate, ALXN1840, were terminated by Alexion/AstraZeneca in April 2023.

Possible new treatments for Wilson's disease (April 2023)

Project: VTX-801

Company: Vivet Therapeutics/ Pfizer

Description: ATP7B gene therapy (rAAV vector)

Status: Ph1/2 Gateway trial began early 2021
https://clinicaltrials.gov/ct2/show/NCT04537377

Project: UX701

Company: Ultragenyx

Description: ATP7B gene therapy (AAV9 vector)

Status: Ph1/2/3 study began H2 2021
https://clinicaltrials.gov/ct2/show/NCT04884815

Project: DPM-1001

Company: Depymed

Description: Copper chelator

Status: Preclinical

Project: DG12P1

Company: Deep Genomics

Description: Antisense oligonucleotide therapy against the Met645Arg mutation in the ATP7B gene

Status: Preclinical

Dietary Copper

All agricultural soils contain copper (about 30 mg/kg in the UK). Therefore, copper is naturally present in the diet and some precautions about which foods should possibly be avoided (or eaten in moderation) may be necessary for patients with Wilson's disease. Along with regular medication, awareness of the amounts of copper in different foods is a sensible strategy. A list of copper values in common foods eaten in the United Kingdom may be found in the Diet section WDSG-UK :: Diet and Copper Content of Foods (wilsonsdisease.org.uk).

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Rupert Purchase; revised May 2023