Praxis Precision Medicines, Inc. announced the outcomes from a recent end-of-Phase 2 meeting with the U. S. Food and Drug Administration (FDA) regarding plans to advance ulixacaltamide into Phase 3 for essential tremor (ET). Use of the modified Activities of Daily Living 11 (mADL111) as the primary endpoint is acceptable. In the Phase 2 Essential1 study, mADL11 was nominally significant (p=0.042).

Agreement to use a single dose of 60 mg for the Phase 3 trials. Base case assumption confirmed for two Phase 3 trials, one of which will be a 12-week, parallel design study and one of which will be a 12-week randomized withdrawal study for stable responders. Safety database required for a New Drug Application (NDA) at the minimum required by ICH guidelines: 300 patients with six-months of exposure and 100 patients with one-year of exposure.

Agreement that the completed and planned clinical pharmacology and toxicology studies would be sufficient for submission of an NDA. The protocols for the Phase 3 trials are being finalized and Praxis intends to submit to the current Investigational New Drug Application shortly. Ulixacaltamide is a differentiated and highly selective small molecule inhibitor of T-type calcium channels designed to block abnormal neuronal burst firing in the Cerebello-Thalamo-Cortical (CTC) circuit correlated with tremor activity.

Ulixacaltamide, the most advanced program within Praxis' Cerebrum™ small molecule platform, is currently in development for the treatment of essential tremor and as a non-dopaminergic treatment for the motor symptoms of Parkinson's disease. Essential Tremor (ET) is the most common movement disorder, affecting roughly seven million people in the United States alone, including approximately two million diagnosed patients. ET is characterized by involuntary rhythmic movement in the upper limbs, with or without tremor in other body locations such as the head, vocal cords, or legs.

These tremors significantly disrupt daily living and are progressive in nature, with increases in tremor severity and amplitude commonly observed over the course of the disease. There is only one approved pharmacotherapy for ET, propranolol, a beta blocker approved by the FDA in 1967, that offers limited efficacy and poor tolerability and that is contraindicated for comorbidities that affect a significant share of the ET population. Other beta blockers and anti-convulsants are used off-label, though similarly are characterized by limited efficacy and tolerability.

For these reasons, approximately 40% of patients who seek pharmacotherapy treatment for ET discontinue within two years.