Efficacy and Safety of a Novel Copper Modulating Agent (WTX-101) for Wilson Disease: Results of a Phase 2, Multi-Center, Open Label Study (P2.026)

Objective: The aim of this study was to evaluate the efficacy and safety of WTX101 in newly diagnosed WD patients. Background: WTX101 (bis-choline tetrathiomolybdate) is a novel copper modulating agent in development for treatment of Wilson Disease (WD). Although WD treatments are available, significant unmet medical needs exist with respect to efficacy, side effects and dosing simplicity. Design/Methods: Patients with WD aged > 18 years, treatment naive or treated for ≤ 2 years with chelation or zinc therapy, initially received 15 or 30 mg WTX101 QD. After 6 weeks dosage was individually guided by laboratory and clinical criteria. Assessments over 24 weeks included neurological and daily activity status using the Unified Wilson Disease Rating Scale (UWDRS), hepatic status, copper parameters and safety. Results: Twenty-eight patients entered the study. Baseline average non-ceruloplasmin copper (NCC) was elevated (3.5μM), 23/28 had neurological manifestations (average UWDRS part III score 22), and all had hepatic involvement. Final results will be presented at the AAN Annual Meeting 2017. Preliminary data indicate that overall neurological (UWDRS part III) and daily activity (UWDRS part II) scores improved in patients with neurological manifestations. Hepatic status largely stabilized or improved. NCC (adjusted for molybdenum) decreased over time on treatment. Other Cu measurements (exchangeable Cu, total serum Cu, 24-hour urinary Cu excretion) indicate a similar de-coppering pattern. Overall WTX101 was well tolerated. Adverse events included reversible elevated liver tests in approximately 30% of patients and neutropenia. Conclusions: Once daily WTX101 treatment over 24 weeks improved neurologic disease, hepatic status and copper control in newly diagnosed WD patients. WTX101 appears well tolerated. Drug induced, paradoxical, neurological deterioration was not observed. Further clinical evaluation of WTX101 is warranted to establish its safety and efficacy for the treatment of WD. Study Supported by: Wilson Therapeutics Disclosure: Dr. Bega has received personal compensation for activities with Teva Pharmaceuticals, AVADIA Pharmaceuticals, Inc. and Cynapsus Therapeutics, Inc as a consultant and speakers. Dr. Bega has received royalty payments from BMJ Best Practices. Dr. Bega has received research support from the National Parkinsons Foundation. Dr. Ala has nothing to disclose. Dr. Askari has nothing to disclose. Dr. Bronstein has nothing to disclose. Dr. Czlonkowska has received personal compensation for activities with Bayer, Univar, Wilson Therapeutics, Roche, GSK, Novartis, Merck, Sanofi, Teva, Wilson Therapeutics. Dr. Czlonkowska has received research support from Bayer, Novartis, Merck, Sanofi, Teva, and Wilson Therapeutics. Dr. Ferenci has received personal compensation for activities with Wilson Therapeutics as a consultant. Dr. Nicholl has nothing to disclose. Dr. Weiss has received personal compensation for activities with Univar BV, Wilson Therapeutics, GMPO, BMS, Novartis, Merck, Bayer, Orphan, and Falk. Dr. Schilsky has received personal compensation for activities with Wilson Therapeutics and Gilead as an advisor and speaker. Dr. Schilsky has received research support from Wilson Therapeutics and WDA.