Wilson Therapeutics AB announced a poster presentation at the International Congress of Parkinson’s Disease and Movement Disorders in Vancouver. The presentation highlighted results from the recently completed Phase 2 trial of WTX101 (bis-choline tetrathiomolybdate), an investigational first-in-class copper-protein binding agent with a unique mechanism of action for the treatment of patients with Wilson Disease. The poster was presented by Danny Bega, MD, Assistant Professor of Neurology at Northwestern University.
WTX101-201 was a 24-week open-label Phase 2 study evaluating the efficacy and safety of WTX101 monotherapy in 28 newly-diagnosed adult patients with Wilson Disease who had received either no prior treatment for Wilson Disease or a standard of care agent for up to two years. As previously reported, the Phase 2 study met its primary endpoint of copper control (p< 0.001) and significant improvements from baseline to week 24 were observed for both patient-reported disability (p< 0.001) and rater-assessed neurological status (p< 0.0001), measured using the Unified Wilson Disease Rating Scale (UWDRS) Part 2 and 3 respectively.
Treatment with WTX101 was generally well-tolerated with most reported adverse events being mild (grade 1) to moderate (grade 2). Importantly, no early neurological worsening upon initiation of WTX101 was observed.
“It was very exciting to participate in this study which was the first clinical trial with a new investigational drug for Wilson Disease in several decades. We are very encouraged by the results as we saw a fast and strong effect on neurological symptoms without any cases of definitive drug-induced worsening of neurological symptoms, which is a potentially devastating side effect that may occur during the initial treatment phase with the existing therapies,” said Danny Bega, MD, Assistant Professor of Neurology at Northwestern University.
“Furthermore, WTX101 can be dosed once daily and was generally well-tolerated so it clearly has the potential to become a very valuable treatment option for patients with Wilson Disease”.
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. WTX101, unlike current treatments for Wilson Disease, enables an alternative copper-protein transport mechanism by rapidly forming copper-protein complexes with high specificity for copper, which quickly de-toxifies copper in both the liver and the blood circulation. WTX101 reduces copper overload by promoting excretion of copper via the bile, the body’s natural route for excess copper elimination.
A Phase 2 study evaluating the efficacy and safety of WTX101 in Wilson Disease patients was successfully completed in 2016. In addition, the active ingredient of WTX101, tetrathiomolybdate, has been tested in several previous clinical studies in Wilson Disease patients. The data from these studies suggest that WTX101 can rapidly lower and control toxic free copper levels and improve clinical symptoms in these patients. The data also suggest that WTX101 is generally well-tolerated and has the potential for a reduced risk of neurological worsening after initiation of therapy. WTX101 is expected to have a once-daily dosing regimen which may potentially translate into improved compliance in Wilson Disease patients, leading to fewer treatment failures and ultimately improved outcomes as a result. WTX101 has received orphan drug designation for the treatment of Wilson Disease in the US and EU.
About Wilson Disease
Wilson Disease is a genetic disorder of impaired copper transport, caused by loss of function of the ATP7B copper-binding protein, leading to impaired excretion of copper into the bile. This results in accumulation of free copper in the bloodstream, and ultimately in damaging accumulation of copper in the liver, brain and other organs. 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. Untreated Wilson Disease inevitably leads to life-threatening hepatic, neurologic or psychiatric problems, or their various combinations.
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 1950’s and 60’s and since then there have been no new treatment options developed for patients with this disease.