Ulixacaltamide
Ulixacaltamide is an investigational new drug developed by Praxis Precision Medicines for the treatment of essential tremor. It is a small molecule designed to selectively inhibit T-type calcium channels, reducing the abnormal neuronal burst firing in the cerebello-thalamo-cortical circuit that is believed to cause tremors.
In October 2025, the drug met its primary endpoints in the pivotal Phase 3 Essential3 clinical program. Following these results, the U.S. Food and Drug Administration granted ulixacaltamide Breakthrough Therapy Designation in December 2025. The company has announced plans to submit a New Drug Application by mid-February 2026.
Medical uses
Ulixacaltamide is being developed specifically for the treatment of essential tremor in adults. If approved, it would represent a new pharmacological class of treatment for the condition, distinct from the current standard-of-care agents such as propranolol and primidone.In December 2025, the FDA granted the drug Breakthrough Therapy Designation, a status intended to expedite the development and review of drugs for serious conditions where preliminary clinical evidence indicates the drug may demonstrate substantial improvement over available therapies.
Mechanism of action
Ulixacaltamide is a selective blocker of T-type calcium channels.Research suggests that the involuntary rhythmic shaking characteristic of essential tremor is driven by abnormal oscillatory activity within the cerebello-thalamo-cortical circuit. Specifically, T-type calcium channels play a key role in generating "burst firing" patterns in neurons within this pathway. By inhibiting these channels, ulixacaltamide is designed to suppress this pathological burst firing and reduce tremor amplitude without causing the widespread central nervous system depression often associated with non-selective treatments.
History
Discovery and early development
The compound was originally discovered by Zalicus Inc. and was known as Z-944. It was later acquired by Praxis Precision Medicines and renamed PRAX-944.Clinical trials
The drug's efficacy was evaluated in the Phase 2 "Essential1" study, which showed improvements in daily living activities scores.In 2025, Praxis completed the "Essential3" Phase 3 program, which consisted of two concurrent decentralized studies:Study 1 : A 12-week randomized, double-blind, placebo-controlled trial. The study met its primary endpoint, demonstrating a statistically significant improvement in the Modified Activities of Daily Living score for patients on ulixacaltamide compared to placebo.Study 2 : An 8-week open-label period followed by a randomized withdrawal phase. This study also met its primary endpoint, showing that 55% of patients maintained their response on ulixacaltamide compared to 33% on placebo.
These positive results followed a February 2025 interim analysis by an Independent Data Monitoring Committee that had initially recommended discontinuing the study due to perceived futility. Praxis elected to continue the trial, ultimately achieving statistical significance in the final readout.