Maintenance of Response and Durability of Effect with Ulixacaltamide in Essential Tremor: Topline Phase Three Results from Essential3 Study Two (Randomized Withdrawal Study)
Jill Farmer1, Salima Brillman2, Alexander Shtilbans3, Monique Giroux4, Melanie Fridley4, Kimberly Crimin4, Minao Tang4, Taylor Crush4, Claudio Santos4, Steven Petrou4, Alyssa Wyant4, Megan Sniecinski4, Marcio Souza4
1BoroNeuro, Hopewell, NJ, USA, 2Parkinson's Disease and Movement Disorders Center of Silicon Valley, Palo Alto, CA, USA, 3Hospital for Special Surgery, Department of Neurology, New York, NY, USA, 4Praxis Precision Medicines, Boston, MA, USA
Objective:
Assessing maintenance of response and durability of effect of ulixacaltamide in essential tremor (ET) as part of the pivotal Phase 3 Essential3 Program.
Background:
ET is a progressive neurologic disorder characterized by involuntary tremor that impairs daily activities and quality-of-life. Current therapies offer limited benefit, and discontinuation due to tolerability, modest efficacy or limited durability remains common. Ulixacaltamide is a selective T-type calcium channel (TTCC) modulator in development for ET. The Essential3 Program comprised 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:
Study 2 was a randomized, double-blind, placebo-controlled trial designed to assess durability of ulixacaltamide hydrochloride. Participants aged 18–85 years with ET (symptoms ≥3 years; if on ET medication(s), stable dose for ≥28 days pre-screening) received ulixacaltamide hydrochloride 60mg QD (after 2-week titration) during a blinded 8-week lead-in. Participants meeting predefined responder criteria were re-randomized 1:1 to continue treatment or switch to placebo for 4 weeks. The primary endpoint was the proportion of responders maintaining response defined as ≥3-point change in mADL11 (TETRAS-ADL items 1-11, modified score) at Day 84. Secondary endpoints included rate of disease improvement, Patient/Clinical Global Impression scores, and safety outcomes.
Results:
A total of 238 participants were enrolled. The primary endpoint was met, with topline results to be presented.
Conclusions:
Essential3 is the only ongoing Phase 3 Program in ET, with Study 2 representing the first registrational study exploring the maintenance of effect following pharmacologic TTCC modulation with ulixacaltamide. Findings highlight ulixacaltamide's potential to redefine the treatment landscape and address the persisting impact on daily life in patients with ET.
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