Praxis Reports Positive Phase III Results for Ulixacaltamide in Essential Tremor

Praxis Precision Medicines has shared positive data from its Phase III Essential3 clinical trial program (NCT06087276) assessing ulixacaltamide in essential tremor (ET). Across two studies, the small molecule inhibitor demonstrated statistically significantly improvements in both tremor control and daily functioning.¹

Study 1 shows significant improvement in daily functioning

In Study 1 of Essential3, a placebo-controlled parallel group study:

• Patients receiving ulixacaltamide achieved a mean improvement of 4.3 points from baseline in the Modified Activities of Daily Living 11 (mADL11) score at Week 8, meeting the primary endpoint (p<0.0001).
• All key secondary endpoints including rate of disease improvement over 12 weeks, Patient Global Impression of Change, and Clinical Global Impression of Severity, were statistically significant (p<0.001).

Study 2 confirms sustained efficacy in withdrawal phase

In Study 2, a randomized withdrawal study:

• The primary endpoint was met, with topline data showing superior maintenance of effect with ulixacaltamide compared to placebo (p=0.0369).
• The first key secondary endpoint, rate of disease improvement during randomized withdrawal, also favored ulixacaltamide (p=0.0042).

Overall, ulixacaltamide was generally well tolerated, with no drug-related serious adverse events and a safety profile consistent with earlier studies.

In a press release, Salima Brillman, MD, Founder, Parkinson's Disease and Movement Disorders Center of Silicon Valley, co-lead investigator of the E3 program, said: “This is incredibly exciting news, for the first time we have a medication designed specifically for our ET patients. 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 their independence and improve their daily functioning in meaningful ways.”

Trial continuation followed early recommendation for discontinuation

This latest readout actually follows an earlier recommendation to halt the trial. In February, the Independent Data Monitoring Committee (IDMC) overseeing the interim analysis of Study 1 of Essential3 recommended that the study be discontinued due to futility, citing results from the time were unlikely to meet the primary efficacy endpoint based on the statistical model.2

Despite this, Praxis continued with the trial given the advanced state of enrollment the program was already in.

Decentralized Phase III design supports robust findings

The Essential3 Phase III program was based in the US using a decentralized design, with participants randomized 2:1 between Study 1 and Study 2.

• Study 1 was a 12-week trial enrolling 473 patients randomized 1:1 to ulixacaltamide or placebo. The primary endpoint was change from baseline in mADL11 score at Week 8.
• Study 2 enrolled 238 patients who received ulixacaltamide for 8 weeks; those achieving ≥3-point improvement in mADL11 were re-randomized to placebo or continued ulixacaltamide for 4 more weeks. The primary endpoint was the proportion maintaining response.
• Two additional pre-specified hypotheses compared pooled ulixacaltamide arms from both studies to the placebo arm of Study 1.

Praxis prepares for FDA discussions following strong results

In the press release, Marcio Souza, president and chief executive officer of Praxis, said: “To all the patients living with ET, I am thrilled with the results of the Essential3 Program. All of us at Praxis will be forever indebted to the bravery you have demonstrated participating in the program, in the face of such a debilitating condition. Patients in Essential3 had been living with essential tremor for an average of 30 years, with worsening symptoms and no effective treatment options. In just 15 months of recruitment, we had over 200,000 people interested in participating in this study, which is a powerful reflection of the large unmet need for a therapy like ulixacaltamide. We look forward to the opportunity to have a pre-NDA meeting with the FDA soon to discuss the potential NDA.”

References

1. Praxis Precision Medicines Announces Positive Topline Results from Two Pivotal Phase 3 Studies of Ulixacaltamide HCl in the Essential3 Program for Essential Tremor. News release. Praxis Precision Medicines. October 16, 2025. Accessed October 16, 2025. https://ir.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-announces-positive-topline-results-1

2. Praxis Precision Medicines Provides Update on Essential3 and Corporate Update. News release. Praxis Precision Medicines. February 28, 2025. Accessed October 16, 2025. https://investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-provides-update-essential3-and