Biogen and Sage Therapeutics Discontinue Development of SAGE-324 for Essential Tremor Following Mid-Stage Trial Failure

1. Trial Failure: Biogen and Sage Therapeutics announced the failure of their Phase 2 KINETIC 2 study of SAGE-324 (BIIB124) for the treatment of essential tremor, as the drug did not demonstrate a statistically significant dose-response relationship on the primary endpoint.
2. Discontinuation of Development: The companies have decided to halt the ongoing open-label safety study of SAGE-324 in essential tremor and will not pursue further clinical development of the drug for this indication.
3. Mechanism of Action: SAGE-324 is an oral neuroactive steroid that binds to both synaptic and extrasynaptic GABA A receptors, enhancing inhibitory activity in the brain.
4. Adverse Events: The trial showed a dose-response relationship for central nervous system depressant treatment-emergent adverse events, leading to a significant number of study dropouts due to toxicities.
5. Future Plans: Biogen and Sage are evaluating next steps for the development of SAGE-324 in other indications, but no specific plans have been announced.
6. Background: In 2020, Biogen invested over $1 billion in Sage Therapeutics, gaining access to several of Sage's candidates, including SAGE-324 and zuranolone (marketed as Zurzuvae for postpartum depression).