Abstract Details

To evaluate the neurologic and clinical outcomes of tiomolibdate choline (TMC) compared with standard-of-care (SoC) in Wilson disease (WD) patients with neurologic symptoms.

Wilson disease (WD) is a rare genetic disorder where excess copper (Cu) accumulation causes progressive neurologic disability. Tiomolibdate choline (TMC; ALXN1840) is an oral, once-daily, high affinity Cu-binding agent. This analysis evaluates outcomes in neurologic WD patients, a population at greater risk of symptomatic worsening on current WD therapy than asymptomatic patients.

In the open-label Phase 3 FoCus trial (NCT03403205), 207 WD patients were randomized 2:1 to TMC or SoC for 48 weeks (W), with an optional TMC extension phase. Neurologic and clinical outcomes were analysed at 48W (primary) and 96W (extension) for patients with neurologic symptoms at baseline, defined as Unified WD Rating Scale [UWDRS] Part III score exceeding the minimum clinically important difference [MCID] of 4.668.

Neurologic WD patients treated with TMC (n=77) demonstrated increasing clinical benefit over time, with statistically significant improvements in UWDRS Part III observed at 48W and continuing through 96W (mean change: −7.2; p<0.001). Benefit of TMC over SoC was evident by 48W, with significant UWDRS Part III improvement in the TMC arm (p=0.002) but not the SoC arm (p=0.235). Additionally, fewer TMC patients worsened by ≥MCID at 48W vs. SoC (9% vs 25%). Disease improvement per Clinical Global Impression-Improvement (CGI-I) scale was statistically significantly greater for TMC vs. SoC at 48W (p=0.003).

In neurologic WD patients, 48 weeks of TMC treatment led to greater clinical benefit than SoC, with continued improvement through 96 weeks. These findings support the potential for TMC to improve neurologic outcomes in this at-risk population.