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Phase 2 Clinical Trial Data for WTX101 Published in The Lancet Gastroenterology & Hepatology

Oct 06, 2017

Wilson Therapeutics (publ.) today announced that data from a Phase 2 trial of WTX101 (bis-choline tetrathiomolybdate), an investigational oral first-in-class copper-protein-binding agent for the treatment of patients with Wilson Disease, has been published online in The Lancet Gastroenterology & Hepatology and will be available in print in the December issue. The results show that treatment with WTX101 induces rapid copper control, significantly reducing free copper levels by 72% from baseline after approximately 3 months, and is associated with significant early improvements in neurological symptoms and disability. The study data have previously been reported at medical conferences but this is the first time the complete study results are available in a peer-reviewed scientific journal.

“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 Prof. Karl Heinz Weiss, University Hospital of Heidelberg, Germany, a principal investigator in the trial and lead author of the publication.

“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”, said Michael Schilsky, MD, Professor of Medicine and Surgery at Yale University, USA, also a principal investigator in the trial and lead author of the publication.

The publication entitled Bis-choline tetrathiomolybdate in patients with Wilson’s disease: an open-label, multicentre, phase 2 study can be found online at

Summary of data from the WTX101-201 Phase 2 study
WTX101, given mostly once daily, was associated with rapid control of copper such that mean levels of free non-ceruloplasmin bound copper (NCCcorrected) were below the upper limit of normal in patients by week 12 (p< 0.001). At 24 weeks, 71% of patients (p< 0.0001) met the primary endpoint, achieving or maintaining normalized levels of copper or experiencing a ≥25% reduction in copper levels from baseline. Overall, mean copper level at baseline was reduced by 72% at week 24 (mean change from baseline: -2.4±0.4 µM; p< 0.0001).

Disease-related patient-reported disability measured by the Unified Wilson Disease Rating Scale (UWDRS) Part II, improved from mean 6.6 at baseline to 4.1 at week 24 (p< 0.0001).

Neurological disease, assessed by UWDRS Part III, was significantly improved from mean 22.8 at baseline to 16.6 at week 24 (p< 0.0001). There appeared to be no case of paradoxical neurological worsening attributed to the study drug after treatment initiation.

Liver function, as measured by standard liver function tests such as International Normalized Ratio (INR) and albumin, as well as liver-specific composite scores (MELD and the Modified Nazer Score), remained unchanged throughout the study.

The clinical benefits demonstrated were reflected by significant improvements in mean EQ VAS scores (p=0.0024), indicating improved patient-reported quality of life.

Treatment with WTX101 was generally well tolerated and most adverse events (AEs) were mild or moderate in intensity. As previously reported, early elevations in liver tests were observed in 39% of the patients. These occurred at doses 30 mg/day or higher, were mostly mild or moderate, all asymptomatic, and normalized within 1–2 weeks after dose adjustments and/or drug holiday. Bilirubin remained unchanged, indicating absence of severe liver injury. Two patients had leukopenia and one thrombocytopenia; all recovered after dose adjustments. Few gastrointestinal or skin events related to study treatment were reported. Eleven serious AEs (SAEs) were reported in seven patients and included psychiatric disorders, gait disturbance, liver test increases, liver test increase with agranulocytosis and decline in neurological functioning (the latter case assessed as likely due to natural disease progression although causality was not ruled out). The seven SAEs categorized as psychiatric disorders and as gait disturbance were assessed as remote/unlikely related to study drug, whereas the relationship for the remaining four events was assessed as possible or probable. Three patients discontinued the study due to reversible liver test abnormalities (not associated with bilirubin increases); two patients discontinued due to psychiatric (behavioral) disease leading to inability to follow the study protocol and one patient discontinued due to decline in neurological functioning.

About the Phase 2 study
WTX101-201 was a 24-week open-label Phase 2 study evaluating the efficacy and safety of WTX101 monotherapy in 28 newly diagnosed patients with Wilson Disease, aged 18 years and older, who had received either no prior treatment for Wilson Disease or a standard of care agent for up to two years. Patients recruited in the study had various degrees of hepatic impairment at the time of enrollment and the majority also had neurological symptoms at study start. The study was conducted at 11 sites in the US and Europe. Patients received WTX101 at individualized doses between 15 and 120 mg/day. The primary endpoint was defined as achieving or maintaining normalized levels of less than 2.3 µM 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). Secondary endpoints included reduction of serum free copper from baseline, neurological disability and status measured as Unified Wilson Disease Rating Scale (UWDRS) part II and III respectively, liver status measured with the Modified Nazer Score and quality of life measured with the EuroQOL 5 Dimensions Visual Analogue Scale (EQ VAS). A 36-month extension phase of the study is ongoing.

About WTX101 (bis-choline tetrathiomolybdate)
WTX101 (bis-choline tetrathiomolybdate) is a first-in-class copper-protein-binding agent with a unique mechanism of action, under investigation as a novel therapy for Wilson Disease. In contrast to current treatments, WTX101 provides an alternative copper-protein binding mechanism by forming a tripartite complex with copper and albumin. WTX101 thereby detoxifies excess copper in both liver and blood, and promotes copper clearance through biliary excretion (the body’s natural route of elimination).

A Phase 2 study evaluating the efficacy and safety of WTX101 in Wilson Disease patients has successfully been completed. In addition, the active moiety of WTX101, tetrathiomolybdate, has been tested in several previous clinical studies in Wilson Disease patients. The data from these studies suggest that WTX101 can lower and control free copper levels, and improve symptoms and associated disabilities. The data also suggest that WTX101 is generally well tolerated with a low risk of neurological worsening. The tolerability profile and the expected once-daily dosing regimen have the potential to improve compliance in Wilson Disease patients, leading to fewer treatment failures and ultimately improved outcomes. WTX101 has received orphan drug designation for the treatment of Wilson Disease in the US and EU.

In addition, WTX101 has shown potential as a treatment for several other medical conditions including Amyotrophic Lateral Sclerosis (ALS). WTX101 has received US orphan drug designation for the treatment of ALS. 

About Wilson Disease
Copper is an essential trace element that plays a critical role in key physiological cellular processes. Due to its toxic potential, copper is normally tightly bound to copper-carrying proteins inside the liver, and excess copper is eliminated from the body via biliary excretion. Wilson Disease is a rare genetic disorder of impaired copper transport and excretion, caused by loss of function of the ATP7B copper-binding protein. This leads to copper overload in the liver, release of free copper into the blood, and damaging accumulation of copper in the brain and other organs. Untreated Wilson Disease inevitably leads to various combinations and severity of hepatic, neurologic and psychiatric symptoms, and is ultimately fatal.

Wilson Disease affects approximately one in every 30,000 people worldwide, corresponding to a prevalence of approximately 10,000 patients in the US and 15,000 patients in the EU. The therapies currently being used in Wilson Disease were introduced in the 1950s and 60s. Since then, no new treatment options have been developed and considerable unmet medical needs still exist.

About Wilson Therapeutics
Wilson Therapeutics is a biopharmaceutical company, based in Stockholm, Sweden, that develops novel therapies for patients with rare diseases. Wilson Therapeutics’ lead product, WTX101, is in development as a novel treatment for Wilson Disease. A Phase 2 clinical study has been successfully completed and preparations for a pivotal Phase 3 study are ongoing. Wilson Therapeutics is listed in the Mid Cap segment on Nasdaq Stockholm with the stock ticker WTX.

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For further information contact:
Jonas Hansson, CEO, Wilson Therapeutics AB
Telephone: +46 8 796 00 00

Wilson Therapeutics AB (publ)
Corp. Reg. No. 556893-0357
Kungsgatan 3
SE-111 43 Stockholm