Objective: To assess the breadth of functional improvement in adults with essential tremor (ET) treated with ulixacaltamide in the Phase 3 Essential3 program.

Background: ET is a chronic, progressive neurological disorder affecting approximately 7 million in the U.S. Functional disability is reported in >85% of patients, impacting daily activities including writing, eating, dressing, and social engagement. While composite measures of tremor-related activities of daily living (ADL) capture overall impairment, itemlevel analysis of therapeutic effects can further identify which specific tasks improve with treatment and the relative magnitude of benefit across domains. Understanding the hierarchy of improvement across individual ADL domains can therefore enrich characterization of realworld treatment effects.

Method: Essential3 Study 1 (NCT06087276) was a Phase 3, decentralized, randomized, double-blind, placebo-controlled, parallel-design study. Adults aged 18–85 years with ET of ≥3 years’ duration and moderate-to-severe disability were randomized 1:1 to ulixacaltamide 60 mg or placebo for 12 weeks (mITT: N=432). Standardized effect sizes (Cohen’s d) were calculated for each individual ADL item at Day 56 to characterize the relative magnitude of treatment effects of ulixacaltamide, a selective T-type calcium channel modulator, across functional domains.

Results: Ulixacaltamide demonstrated improvement relative to placebo across the 12 ADL domains at Day 56. The largest relative treatment effects were observed in motor-intensive functional tasks including drinking, carrying trays or plates, pouring, and feeding. All domains showed superiority for ulixacaltamide, with separation from placebo by Day 14 that was sustained through Day 84 across all domains, including social impact.

Conclusion: Essential3 Study 1 item-level analysis reveals broad functional improvement with ulixacaltamide across all ADL domains affected by ET, including social impact. These findings demonstrate that clinically meaningful ulixacaltamide treatment benefits extend beyond upperextremity motor tasks, complementing primary composite measure findings, and providing clinicians with granular insight into the full breadth of expected therapeutic benefit.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ulixacaltamide-demonstrates-broad-functional-improvement-across-individual-domains-of-activities-of-daily-living-in-essential-tremor/