Assessing Clinically Meaningful Improvement Associated with Ulixacaltamide Treatment in Adults with Essential Tremor on Concomitant Propranolol: Findings from Essential1
Monique Giroux1, Alex La Croix1, Jeff Zhao1, Gene Wright1, Henry Jacotin1, Megan Sniecinski1, Aubryn Samaroo1, Candace Griffin1, Richard Able1, Claudio Santos1, Marcio Souza1
1Praxis Precision Medicines
Objective:
Assessing clinically meaningful change related to ulixacaltamide (PRAX-944) treatment in adults with essential tremor (ET) in combination with propranolol.
Background:

Despite being one of the most common movement disorders, public recognition of ET and its impact remain low. Furthermore, up to 50% of patients do not respond to propranolol, the only FDA indicated medication for ET, prompting the need for more effective and better tolerated therapies. Ulixacaltamide, a novel, selective T-type calcium channel blocker specifically designed for ET patients, showed meaningful improvement in TETRAS Activities of Daily Living (ADL) measures in Essential1 (NCT05021991) alongside a well-tolerated safety profile. Here we assess the effect of ulixacaltamide treatment in patients receiving propranolol. 

Design/Methods:

133 adults with moderate-to-severe ET were enrolled in Essential1, an 8-week, double-blind, placebo-controlled study with optional Extension. Participants were randomized to ulixacaltamide QAM or placebo followed by blinded lead-in (DBLI; through week 14) during which all participants were titrated to ulixacaltamide. Change in mADL11 (TETRAS-ADL items 1-11 with modified score) for ulixacaltamide compared to placebo was assessed in a subset of participants (n=36) on a stable propranolol dose throughout the study. Corresponding responder analyses were conducted based on clinically meaningful within-patient change in mADL11 defined as a minimum 3-point improvement.

Results:
Ulixacaltamide demonstrated incremental benefit to patients on propranolol (-1.07 mADL11 change vs. -0.61 for propranolol and placebo, week 8) with a generally well-tolerated safety profile across groups. At week 8, 48% of patients on propranolol and ulixacaltamide achieved meaningful improvement vs. 25% for patients on propranolol and placebo, with incremental benefit further observed by week 14.
Conclusions:
Building on findings from Essential1 and focusing on measures determined to be most meaningful to patients, these results highlight the potential for ulixacaltamide to revolutionize the treatment of ET, with evidence of meaningful improvement both alone and in combination with chronic propranolol use.
10.1212/WNL.0000000000205217