Phase 2 Wilson Disease Study Shows Encouraging Results

Jim Radke, PhD

This week in Lancet Gastroenterology & Hepatology, Karl Heinz Weiss, MD and colleagues have published results from a Phase 2, open label study looking at the safety and efficacy of bis-choline tetrathiomolybdate (WTX101) in patients with Wilson's disease.

The data released are considered so promising that the developers of the drug, Wilson Therapeutics Inc., are planning a pivotal Phase 3 study.

Wilson's disease is a genetic disorder in which the person is unable to properly eliminate copper from vital organs such as the liver and brain. If left untreated, Wilson's disease is fatal. If diagnosed early however, it is treatable condition and many people with Wilson’s disease can live normal lives.
Wilson’s disease is treatable and proper therapy can stop further (and could potentially reverse) progression of the condition.

Current treatment options are chelating agents designed to remove excess copper Penicillamine (Cuprimine, Depen) and Trientine (Syprine). Patients with Wilson’s disease may also require a low copper diet.

Despite these available treatments, more options are necessary and Wilson’s Therapeutics has developed WTX101 which not only binds to copper, but also promotes copper clearance through biliary excretion.

In the study, 28 newly-diagnosed Wilson’s disease patients (18 years and older) received WTX101 at individualized doses ranging from 15 to 120 mg/day. The primary endpoint was defined as achieving or maintaining normalized levels of free blood copper, or reaching a reduction of at least 25% in free copper in blood from baseline, after 24 weeks of treatment.

Free copper in blood was measured as non-ceruloplasmin-bound copper, corrected for the amount of copper bound to tripartite tetrathiomolybdate-copper-albumin complexes in blood (NCCcorrected).

After 24 weeks of treatment, 71% of patients (P <  .0001) and the mean copper levels decreased by 72% over the course of the study (mean change from baseline: -2.4±0.4 µM; P <  .0001)

A total of 11 serious adverse events (AEs) were reported in 7 (25%) patients in the study, including psychiatric disorders (6 events in 4 patients), gait disturbance (1 event), elevated liver aminotransferases (2 events in 2 patients), and decline in neurological functioning (1 event). Of those 11 events, 7 were deemed to be not likely related to the study drug while 4 were likely related to the drug.

In a news release, the lead author of the study, Karl Heinz Weiss, M.D., Professor of Medicine at the University Hospital of Heidelberg, Germany, shared their enthusiasm of the results.

“This is the first global prospective multi-center trial conducted in Wilson Disease and I am especially encouraged by the rapid and clinically meaningful improvement of disease related symptoms, and the apparent lack of paradoxical neurological worsening after WTX101 treatment initiation, an adverse effect that unfortunately is seen in some patients when starting chelators. Furthermore, the once-daily dosing of WTX101 can possibly minimize the treatment burden, leading to better long-term compliance and treatment outcomes. All Wilson Disease patients need life-long therapy but current treatment options have significant limitations. WTX101 has the potential to bring new hope to patients and their caregivers,” said Weiss. 

Michael Schilsky, M.D., Professor of Medicine and Surgery at Yale University, USA, added: “Patients with Wilson Disease can be severely affected by hepatic, neurologic and psychiatric symptoms. The main treatment goal is to quickly remove and detoxify excess copper in patients without worsening their disease, and then to maintain copper control. The rapid biochemical and clinical improvements seen with WTX101 are possibly related to its novel, copper-specific mechanism of action which acts directly in the liver and lowers toxic free copper levels in the blood. I am very excited about the results achieved so far as it provides further evidence of the potential of WTX101 as a novel and effective treatment for patients with Wilson Disease.”

Weiss KH, Askari FK, Czlonkowska A, et al. Bis-choline tetrathiomolybdate in patients with Wilson's disease: an open-label, multicentre, phase 2 study. Lancet Neurol. Published online ahead of print. October 5, 2017. DOI:

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