2026 American Academy of Neurology Abstract Website

Alexander Shtilbans¹, Jill Farmer², Salima Brillman³, Monique Giroux⁴, Melanie Fridley⁴, Kimberly Crimin⁴, Minao Tang⁴, Taylor Crush⁴, Claudio Santos⁴, Steven Petrou⁴, Alyssa Wyant⁴, Megan Sniecinski⁴, Marcio Souza⁴
¹Hospital for Special Surgery, Department of Neurology, New York, NY, USA, ²BoroNeuro, Hopewell, NJ, USA, ³Parkinson's Disease and Movement Disorders Center of Silicon Valley, Palo Alto, CA, USA, ⁴Praxis Precision Medicines, Boston, MA, USA

Objective:

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

Background:

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.

Design/Methods:

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.

Results:

Data included a total of 390 participants receiving ulixacaltamide hydrochloride 60mg QD across Studies 1 and 2, and 233 placebo participants from Study 1. Within each combined analysis, the primary endpoint was met. Topline results will be presented.

Conclusions:

Essential3 is the only ongoing Phase 3 Program in ET, designed to evaluate the clinical benefit of pharmacologic TTCC modulation with ulixacaltamide. Positive topline findings highlight ulixacaltamide’s potential as a first-in-class therapy poised to redefine the ET treatment landscape for the first time in several decades.