Objective: The objective of this study was to evaluate the efficacy and safety of 24 week WTX101 treatment in newly diagnosed Wilson Disease (WD) patients.

Background: WTX101 (bis-choline tetrathiomolybdate) is an investigational first in class copper modulating agent for the treatment of WD. Although WD therapies are available, substantial unmet medical needs exist with respect to efficacy, side effects and treatment convenience.

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 once daily. After 6 weeks, dosage was individually guided by laboratory and clinical criteria. Assessments included copper control, neurological and disability status using the Unified Wilson Disease Rating Scale (UWDRS), hepatic status and safety.

Results: Twenty-eight patients entered the study. Baseline average non-ceruloplasmin copper (NCC) was elevated (3.6µM) and 23/28 had neurological manifestations (average UWDRS part 3 score 22.8). The primary endpoint of copper control was met in 79% of patients (p<0.001). Mean reduction of NCC levels was 77% (p<0.0001). Both neurological status (p<0.0001) and disability (p<0.001) improved as measured by UWDRS Parts 3 and 2, respectively. In addition, liver status, as measured by the Modified Nazer Score, was stabilized or improved in the majority of patients. Treatment with WTX101 was generally well tolerated with most reported adverse events being mild (grade 1) to moderate (grade 2). Reversible liver test elevations were observed in 39% of patients and these elevations were generally mild to moderate, asymptomatic and normalized with dose adjustments. No initial drug-induced neurological worsening was observed upon treatment initiation with WTX101.

Conclusions: Once daily WTX101 treatment has the potential to rapidly lower and control free copper, and improve neurological status and disability in patients with WD. Additionally, WTX101 was generally well-tolerated with no observed cases of neurological worsening upon initiation of WTX101. Together with its simplified dosing, WTX101 has the potential to address the unmet needs in WD. Further clinical evaluation of WTX101 is warranted to establish its safety and efficacy for the treatment of WD.

References: This study was supported by Wilson Therapeutics.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/wtx101-a-novel-copper-modulating-agent-for-wilson-disease-demonstrates-efficacy-and-safety-in-a-phase-2-multi-center-open-label-study/