FDA Grants Breakthrough Therapy Designation for Ulizacaltamine in Essential Tremor

Announced on December 29, 2025, by Praxis Precision Medicines Inc., the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for ulixacaltamine for the treatment of patients with essential tremor.1

“The granting of the Breakthrough Therapy Designation for ulixacaltamide, based on the Essential3 program, further underscores its potential to address the substantial unmet need in patients with ET,” said Marcio Souza, president and chief executive officer, in a statement. “We recently completed a series of positive interactions with the FDA, that, together with this BTD, are enabling us to advance this promising treatment faster to patients. We are diligently preparing for the filing of the ulixacaltamide NDA, which we expect in early 2026.”1

The most common movement disorder globally, essential tremor, affects an estimated 7 million individuals in the United States. Propranolol, a beta-blocker, remains the only pharmacotherapy previously approved for ET. Ulixacaltamide is a differentiated, highly selective small-molecule inhibitor of T-type calcium channels designed to block abnormal neuronal burst firing in the cerebello-thalamo-cortical circuit associated with tremor activity, with the potential to expand treatment modalities.1

The FDA decision was supported by positive topline data from the phase 3 Essential3 program, which consisted of 2 simultaneously enrolled studies using a decentralized design conducted in the United States. Across the program, participants were allocated in a 2:1 blinded randomization.1,2

Study 1 was a double-blind, parallel-group, placebo-controlled trial in which patients were randomized 1:1 to receive either ulixacaltamide or placebo for 12 weeks. The primary endpoint was the change from baseline in the modified Activities of Daily Living 11-item scale (mADL11) at Week 8.2

Study 2 was a stable-responder randomized withdrawal study in which participants received ulixacaltamide for 8 weeks. Patients who achieved a ≥3-point improvement from baseline in mADL11 were then randomized to placebo or continued ulixacaltamide for an additional 4 weeks. The primary endpoint assessed the proportion of patients who maintained response with ulixacaltamide compared with placebo.2

Across both studies, key secondary endpoints included the rate of disease improvement, defined as the slope of mADL11 change, Patient Global Impression of Change (PGI-C), and Clinical Global Impression of Severity (CGI-S).2

Study 1 included 473 patients, and study 2 enrolled 238 patients with essential tremor.2

In Study 1, ulixacaltamide demonstrated a statistically significant and clinically meaningful 4.3-point mean improvement in mADL11 at Week 8 (P <.0001). Treatment effects were observed as early as Week 2 and sustained through the 12-week dosing period. All key secondary endpoints achieved statistical significance.2

In Study 2, among patients meeting responder criteria, 55% of those receiving ulixacaltamide maintained response compared with 33% in the placebo group (P = .0369; Odds Ratio [OR], 2.7; 95% Confidence Interval [CI], 1.06-6.92). The first key secondary endpoint, rate of disease improvement, achieved statistical significance. PGI-C and CGI-S results numerically favored ulixacaltamide but did not reach statistical significance.2

“This is incredibly exciting news. For the first time, we have a medication designed specifically for our ET patients,” said Salima Brillman, MD, founder of the Parkinson’s Disease and Movement Disorders Center of Silicon Valley and co-lead investigator of the Essential3 program. “As a clinical researcher and movement disorder specialist, it is very rewarding to see such positive results with the potential to truly change lives. Ulixacaltamide represents more than data on a chart; it is a real opportunity to help people regain independence and improve daily functioning in meaningful ways.”2

References

1. Praxis Precision Medicines, Inc. Praxis Precision Medicines Announces the FDA Has Granted Breakthrough Therapy Designation for Ulixacaltamide HCl in Essential Tremor. GlobeNewswire News Room. Published December 29, 2025. Accessed December 29, 2025. https://www.globenewswire.com/news-release/2025/12/29/3210888/0/en/Praxis-Precision-Medicines-Announces-the-FDA-Has-Granted-Breakthrough-Therapy-Designation-for-Ulixacaltamide-HCl-in-Essential-Tremor.html

2. ‌Praxis Precision Medicines Announces Positive Topline Results from Two Pivotal Phase 3 Studies of Ulixacaltamide HCl in the Essential3 Program for Essential Tremor - Praxis Precision Medicines, Inc. Praxis Precision Medicines, Inc. Published 2025. Accessed December 29, 2025. https://investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-announces-positive-topline-results-1