Abstract Details

Title Assessing Clinically Meaningful Improvement Associated with Ulixacaltamide Treatment in Adults with Essential Tremor on Concomitant Propranolol: Findings from Essential1

Topic Movement Disorders

Presentation(s) S30 - Movement Disorders: Clinical Trials in Movement Disorders (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

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.

Objective Assessing clinically meaningful change related to ulixacaltamide (PRAX-944) treatment in adults with essential tremor (ET) in combination with 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.

Authors/Disclosures
Richard A. Able, Jr., PhD PRESENTER	Dr. Able has received personal compensation for serving as an employee of Praxis Medicines. Dr. Able has received personal compensation for serving as an employee of PTC Therapeutics. Dr. Able has stock in PTC Therapeutis. Dr. Able has stock in Praxis Medicines. Dr. Able has received personal compensation in the range of $0-$499 for serving as a Employee with PTC therapeutics.
Monique L. Giroux, MD	Dr. Giroux has received personal compensation for serving as an employee of Praxis Precision Medicine.
Alex La Croix (Praxis Precision Medicines)	Mr. La Croix has received personal compensation for serving as an employee of Praxis Precision Medicines. Mr. La Croix has stock in Praxis Precision Medicines.
Jeff Zhao	No disclosure on file
Gene Wright (Praxis Precision Medicines)	No disclosure on file
Henry Jacotin (Praxis)	No disclosure on file
Megan Sniecinski	Megan Sniecinski has received personal compensation for serving as an employee of Praxis Precision Medicines. Megan Sniecinski has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Praxis Precision Medicines.
Aubryn Samaroo (Praxis Precision Medicines)	No disclosure on file
Candace Griffin	No disclosure on file
Claudio Santos	No disclosure on file
Marcio Souza	No disclosure on file