Sage Therapeutics and Biogen announce SAGE 324 (BIIB124) did not demonstrate a statistically significant dose-response relationship on the primary endpoint in participants with essential tremor

The KINETIC 2 Study did not demonstrate a statistically significant dose-response relationship in change from baseline to Day 91 based on the primary endpoint, The Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale (PS) Item 4 (upper limb) total score, in participants with ET. In addition, there were no statistically significant differences demonstrated for any dose of SAGE-324 versus placebo in the change from baseline to Day 91 on the TETRAS PS Item 4 Total Score or the TETRAS Activities of Daily Living (ADL) Composite Score. Given these results, Sage and Biogen will close the ongoing open label safety study of SAGE-324 in ET and do not plan to conduct further clinical development of SAGE-324 in ET. The companies are evaluating next steps, if any, for other potential indications.

KINETIC 2 Study Results

The KINETIC 2 Study was designed to evaluate the dose-response relationship of different doses of SAGE 324 on upper limb tremor. The study also evaluated the safety and tolerability of SAGE 324. The primary outcome measure was TETRAS PS Item 4 Total Score at Day 91, and the primary analysis assessed the dose-response relationship across SAGE 324 doses on this measure. Additional analyses evaluated the change from baseline to Day 91 on the TETRAS PS Item 4 Total Score and the secondary endpoint, TETRAS ADL Composite Score, for each dose of SAGE-324 versus placebo.

In the study, 147 participants (129 monotherapy and 18 adjunct therapy, on a stable dose of propranolol prior to and during the study) were randomized in approximately equal proportions to placebo, 15 mg, 30 mg, and 60 mg (with uptitration) for a three-month treatment period.

i SAGE 324 did not demonstrate a statistically significant dose-response relationship on the primary endpoint in participants with ET. ii No statistically significant differences were demonstrated between any dose of SAGE 324 and placebo in the change from baseline at Day 91 on the TETRAS PS Item 4 Total Score or TETRAS ADL Composite Score. iii Overall, there was a dose-relationship observed in the incidence of CNS depressant treatment emergent adverse events (TEAEs) and in the frequency of TEAEs leading to study drug discontinuation. iv The most common TEAEs reported in any treatment group were somnolence, dizziness, fatigue, feeling abnormal, headache, and balance disorder. The majority of TEAEs were mild or moderate in intensity.