Sage Therapeutics and Biogen reported topline results from the Phase 2 KINETIC Study evaluating SAGE-324 in the treatment of patients with essential tremor (ET). The study achieved its primary endpoint of a significant reduction in tremor score compared to placebo at Day 29. The treatment was safe and well tolerated. Full data from the KINETIC Study will be shared at future scientific forums and in publications.
KINETIC was a multicenter, randomized, double-blind, placebo-controlled study conducted in 69 patients with essential tremor aged 18 to 80 years old. Patients were randomized 1:1 to receive SAGE-324 (60 mg) or matched placebo once daily in the morning for 28 days. The primary endpoint was to demonstrate a statistically significant reduction from baseline compared to placebo in The Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Item 4 upper limb tremor score on Day 29. The endpoint was reached, with a 36% reduction from baseline in upper limb tremor amplitude in patients receiving SAGE-324 compared to a 21% reduction in patients receiving placebo. Activities of daily living (ADL) scores showed a statistically significant correlation with upper limb tremor score at all timepoints. The most common TEAEs that occurred in ≥10% of patients in the SAGE-324 treatment group and at a rate at least twice as high as that of patients in the placebo group included somnolence (68%); dizziness (38%); balance disorder (15%); diplopia (12%); dysarthria (12%); and gait disturbance (12%).
SAGE-324 is an oral neuroactive steroid (NAS) GABAA receptor positive allosteric modulator (PAM). NAS GABAA receptor PAMs bind to both synaptic and extrasynaptic GABAA receptors, enhancing inhibitory activity of the GABAergic system, the major inhibitory neurotransmission system in the brain. GABA is the primary inhibitory neurotransmitter in the central nervous system and plays a critical role in maintaining balanced neuronal activity in the brain. GABA dysregulation has been implicated in the pathophysiology of ET.
About Essential Tremor
Essential Tremor is a movement disorder leading to uncontrollable shaking of the hands, head, voice, or legs, thus creating difficulty with eating, dressing, writing, and other day-to-day tasks. The only U.S. Food and Drug Administration (FDA) approved pharmacological treatment for ET, Inderal (propranolol), was approved more than 50 years ago. More than 50% of patients with ET experience a sub-optimal response with standard-of-care treatments, highlighting a significant unmet need in care.