Evaluating the overall efficacy and safety of ulixacaltamide in adults with essential tremor (ET) across the pivotal Phase 3 Essential3 Program.

ET is the most common movement disorder, affecting millions worldwide, often with profound impact on daily functioning. Despite its prevalence, there have been no new treatments for ET since propranolol’s approval ~40 years ago, with most therapies discontinued because of tolerability or modest efficacy. Ulixacaltamide is a selective T-type calcium channel (TTCC) modulator in development for ET. The Essential3 Program was designed to provide a comprehensive evaluation of its efficacy and tolerability through two simultaneous 12-week registrational studies, with blinded assignment: Study 1 (parallel-group design) and Study 2 (randomized withdrawal), conducted using a decentralized model, with optional long-term safety extension.

Blinded assignment allowed data to be combined across study group. Combined analysis integrated data through Day56 from 623 participants aged 18–85 years with ET (symptoms ≥3 years; if on ET medication(s), stable dose ≥28 days pre-screening), enrolled across Study 1 (Abstract5370) and Study 2 (Abstract5412). The primary endpoint in each analysis was change from baseline to Day56 in mADL11 (TETRAS-ADL items 1–11, modified score). Secondary endpoints included rate of disease improvement and Patient/Clinical Global Impression scores. Pre-specified hypotheses evaluated overall treatment effect across studies. Subgroup and sensitivity analyses assessed consistency across demographic and clinical factors.