Ulixacaltamide Improves Daily Function in Patients With Essential Tremor

Topline data were announced from two phase 3 trials evaluating ulixacaltamide in patients with essential tremor (ET). 

Ulixacaltamide is a highly selective small molecule T-type calcium channel inhibitor designed to block neuronal bursting in the cerebello-thalamo-cortical circuit linked to tremor activity. The decentralized Essential3 phase 3 program (ClinicalTrials.gov Identifier: NCT06087276) consisted of 2 simultaneous trials in which ET participants on no more than 1 stable ET medication were randomly assigned 2:1 to either Study 1 or Study 2. 

Study 1 was a double-blind, parallel design, placebo-controlled trial. Participants were randomly assigned 1:1 to receive ulixacaltamide (n=199) or placebo (n=233) for 12 weeks. The primary endpoint was the change from baseline to week 8 in Modified Activities of Daily Living 11 (mADL11) score. The mADL11 score ranges from 0 to 33; larger values equate to an increase in direct tremor impact on activities of daily living. 

Findings showed a statistically significant and clinically meaningful improvement in the mADL11 score at week 8 with ulixacaltamide vs placebo (change in mADL11: -4.3 vs -1.7, respectively; P <.0001). Statistical significance was also observed in all key secondary endpoints including the rate of disease improvement (-4.0 vs -1.7; P <.0001), Patient Global Impression of change (PGI-C; 3.3 vs 3.9; P <.0001), and Clinical Global Impression of severity (CGI-S; -0.41 vs -0.12; P =.0007). 

Study 2 was a randomized, stable-responder, withdrawal trial that included 238 patients who initially received ulixacaltamide for 8 weeks. Those who improved by 3 points in mADL11 score from baseline (N=80) were then randomly assigned to receive placebo (n=40) or continue ulixacaltamide therapy (n=40) for an additional 4 weeks. The primary endpoint was the proportion of patients who maintained response, as assessed by change in mADL11 score, after the randomized withdrawal. 

Findings showed 55% of patients receiving ulixacaltamide maintained response compared with 33% of those receiving placebo (P =.037). Additionally, statistical significance was observed for the key secondary endpoint, rate of disease improvement from baseline to day 84 (2.8 vs 5.2 with placebo; P =.004). Other secondary endpoints (PGI-C at day 84 and CGI-S from day 54 to day 84) did not achieve statistical significance, though results were numerically favorable toward ulixacaltamide. 

Ulixacaltamide was well tolerated, with the most common treatment emergent adverse events being constipation, dizziness, euphoric mood, brain fog, headache, paraesthesia and insomnia. No deaths or drug-related serious adverse events were reported. 

“The trial’s innovative home-based design, with participants across all 50 states completing visits from their homes, brings real-world results to the ET community,” said Jill Farmer, DO, MPH, FCPP, DipABLM, BoroNeuro, co-lead investigator of the E3 program. “The ulixacaltamide phase 3 studies allowed us to engage a broad and representative ET population that truly reflects the diversity of those living with this condition, including people who might not have participated in clinical research otherwise. These positive results truly reflect the patient experience and highlight what is most meaningful to those living with essential tremor.”

According to Praxis, additional data from the trials will be shared at an upcoming medical conference and in peer reviewed publications. The Company has submitted a pre-New Drug Application meeting request to the Food and Drug Administration to discuss the requirements for submission.

This article originally appeared on MPR