Sage Therapeutics and Biogen Release Phase 2 KINETIC 2 Results for SAGE-324 in Essential Tremor

Sage Therapeutics, Inc. and Biogen Inc. recently unveiled the topline results from their Phase 2 KINETIC 2 dose-range study of SAGE-324 (BIIB124), an investigational oral drug aimed at treating essential tremor (ET). The findings from the study, however, did not show a statistically significant dose-response relationship on the primary endpoint, which was the change from baseline to Day 91 based on the Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale (PS) Item 4 total score. This assessment focuses on upper limb tremor in participants with ET. Moreover, no statistically significant differences were observed between any dose of SAGE-324 and placebo regarding the primary endpoint or the TETRAS Activities of Daily Living (ADL) Composite Score.

Due to these outcomes, Sage and Biogen have decided to terminate the ongoing open label safety study of SAGE-324 in ET and do not intend to pursue further clinical development of SAGE-324 for this specific condition. The companies are, however, contemplating the next steps for other potential applications of the drug.

Dr. Laura Gault, Chief Medical Officer at Sage Therapeutics, expressed disappointment over the results, emphasizing the urgent need for innovative treatments in the essential tremor field, which has seen little advancement over the past five decades. She extended her gratitude to the essential tremor community and study investigators for their contributions to the research. Despite the setback, Sage remains committed to developing new treatments for brain health conditions.

Dr. Katherine Dawson, Head of Therapeutics Development Unit at Biogen, also acknowledged the disappointment but stressed that the findings contribute to the broader understanding of essential tremor, which might help guide future research and therapeutic strategies. She thanked the study participants and investigators for their invaluable contributions.

The KINETIC 2 Study aimed to evaluate the dose-response relationship of varying doses of SAGE-324 on upper limb tremor, as well as assess the drug’s safety and tolerability. The study's primary outcome measure was the TETRAS PS Item 4 Total Score at Day 91. It also analyzed the change from baseline to Day 91 on this score and the secondary endpoint, the TETRAS ADL Composite Score, for each dose of SAGE-324 compared to placebo. A total of 147 participants were involved in the study, with 129 on monotherapy and 18 on adjunct therapy, all maintaining a stable dose of propranolol prior to and during the study. Participants were randomized in roughly equal numbers to receive placebo, 15 mg, 30 mg, and 60 mg (with dose uptitration) over a three-month treatment period.

SAGE-324, also known as BIIB124, is an investigational oral neuroactive steroid (NAS) GABA_A receptor positive allosteric modulator (PAM). These modulators bind to both synaptic and extrasynaptic GABA_A receptors, enhancing the inhibitory activity of the GABAergic system, which is the primary inhibitory neurotransmission system in the brain. GABA, the main inhibitory neurotransmitter in the central nervous system, plays a crucial role in maintaining balanced neuronal activity in the brain. Dysregulation of GABA has been linked to the pathophysiology of essential tremor. However, the safety and effectiveness of SAGE-324 are yet to be established.

Sage Therapeutics is a biopharmaceutical company focused on developing life-changing brain health medications. The company has already developed two FDA-approved treatments for postpartum depression and continues to advance its pipeline to address unmet needs in brain health. Founded in 2010, Sage is headquartered in Cambridge, Massachusetts.

Biogen, established in 1978, is a leading biotechnology company that focuses on pioneering innovative science to deliver new medicines, thereby transforming patients' lives and creating value for shareholders and communities. The company leverages its deep understanding of human biology to advance first-in-class treatments or therapies that aim for superior outcomes. Biogen’s approach balances bold risks with return on investment to ensure long-term growth.