Phase 2 Trial of SAGE-324 Fails to Meet Primary Endpoint for Essential Tremor
Key Insights
The Phase 2 KINETIC 2 study of SAGE-324 (BIIB124) did not meet its primary endpoint of demonstrating a statistically significant dose-response relationship in essential tremor (search) patients.
No statistically significant differences were observed between any dose of SAGE-324 and placebo in improving upper limb tremor or activities of daily living.
Sage Therapeutics and Biogen will discontinue the open-label safety study and halt further clinical development of SAGE-324 for essential tremor (search).
Sage Therapeutics and Biogen have announced that the Phase 2 KINETIC 2 study of SAGE-324 (BIIB124), an investigational oral drug for essential tremor (search) (ET), did not meet its primary endpoint. The trial failed to demonstrate a statistically significant dose-response relationship in reducing upper limb tremor, as measured by the Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale (PS) Item 4, at Day 91.
The KINETIC 2 study was a dose-ranging trial designed to evaluate the efficacy and safety of SAGE-324 in participants with essential tremor (search). A total of 147 participants were randomized to receive placebo, 15 mg, 30 mg, or 60 mg of SAGE-324 over a three-month treatment period.
Lack of Statistically Significant Improvement
In addition to the primary endpoint, the study also assessed the change from baseline to Day 91 on the TETRAS PS Item 4 Total Score and the TETRAS Activities of Daily Living (ADL) Composite Score for each dose of SAGE-324 compared to placebo. No statistically significant differences were observed in either of these secondary endpoints.
"There has been little innovation in the pharmacological treatment of essential tremor (search) over the past 50 years, and people living with this debilitating condition have a pressing need for new treatment options," said Laura Gault, MD, PhD, Chief Medical Officer, Sage Therapeutics. "We are disappointed that the results of the KINETIC 2 Study do not support further development of SAGE-324 in ET."
Safety and Tolerability
The study revealed a dose-related increase in the incidence of CNS depressant treatment-emergent adverse events (TEAEs) and in the frequency of TEAEs leading to study drug discontinuation. Common TEAEs included somnolence, dizziness, fatigue, feeling abnormal, headache, and balance disorder, with most being mild to moderate in intensity.
Future Plans for SAGE-324
Given the results, Sage and Biogen will discontinue the ongoing open-label safety study of SAGE-324 in ET and do not plan to pursue further clinical development of the drug for this indication. The companies are currently evaluating potential next steps for SAGE-324 in other possible indications.
"We wish to thank the study participants and investigators who made this important research possible. While we share in their disappointment, we believe that the findings add to the collective understanding of this debilitating condition and may help inform the field on potential future research and therapeutic approaches," said Katherine Dawson, MD, Head of Therapeutics Development Unit, Biogen.
About SAGE-324
SAGE-324 is an investigational oral neuroactive steroid (NAS) GABAA receptor (search) positive allosteric modulator (PAM). It is designed to enhance the inhibitory activity of the GABAergic system in the brain. GABA dysregulation has been implicated in the pathophysiology of ET.