Objective: The objective of this study was to characterize neurological manifestations in Wilson Disease (WD) patients and describe specific neurological changes after 24 weeks’ treatment with WTX101.

Background: Substantial unmet needs exist with respect to the efficacy, safety and tolerability of WD treatments. WTX101 (bis-choline tetrathiomolybdate) is an oral investigational first-in-class copper-protein-binding agent, dosed once daily, which rapidly improved disability and neurological status in a prospective 24-week Phase 2 trial in WD.

Methods: Adult patients with WD (treatment naïve or ≤2 years with chelation or zinc therapy) received response-guided individual WTX101 dosing (15-120 mg once daily) for 24 weeks. Changes in neurological status were characterized using the Unified Wilson’s Disease Rating Scale (UWDRS).

Results: Of the 28 enrolled patients, 25 had neurological manifestations. Baseline mean UWDRS Part II (disability) and III (neurological status) scores were 6.6 (SD 10.0; range 0–35) and 22.8 (SD 21.0; range 0–83), respectively. By week 24, both mean [SD] UWDRS Part II score (4.1 [8.2]; p<0.001) and Part III score (16.6 [17.7]; p<0.0001) improved. There was a highly significant predictive relationship between Parts II and III total scores taken over time (p<0.0001). Most common UWDRS Part III abnormalities at baseline were postural arm tremor (71%), dysarthria (68%), gait (61%) and limb dexterity and coordination scale items e.g. alternating hand movements (71%), finger taps (57%), handwriting (54%) and leg agility (54%). Most severely affected items were handwriting and dysarthria (mean [SD] scores 2.0 [0.8] and 1.8 [0.9], respectively). Largest mean improvements (% change) over 24 weeks were observed for handwriting (51.4%), leg agility (40.8%), postural arm tremor (39.5%) and alternating hand movements (35.0%). Grouping total tremor or limb dexterity and coordination items demonstrated similar improvements (34.2% and 29.2%, respectively). WTX101 was generally well tolerated and early drug-induced neurological worsening was not observed.

Conclusions: Neurological manifestations were common in this patient cohort with WD. Improved neurological status after WTX101 treatment correlated with reduced patient-reported disability. Together with its simplified dosing and favorable safety profile, WTX101 has the potential to address unmet needs in WD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neurological-improvement-with-wtx101-treatment-in-a-phase-2-multi-center-open-label-study-in-wilson-disease/