Sage Therapeutics and Biogen have ceased the development of SAGE-324 (BIIB124) for essential tremor following a disappointing phase 2 trial. Despite efforts to address prior tolerability issues, the drug failed to outperform placebo in reducing upper limb tremors over a 91-day period, leading the study to miss its primary endpoint. This outcome forced the partners to close an open-label safety study and shelve further trials of SAGE-324 for this indication, though they are still considering other potential uses for the drug.
The phase 2 trial involved 147 patients randomized to receive one of three doses of SAGE-324 or a placebo. The lack of a statistically significant dose-response relationship on the primary endpoint has raised doubts about the viability of GABAA receptor positive allosteric modulators in treating essential tremor. Following the trial results, Sage's stock plummeted by 27%, with Biogen’s stock also slipping slightly. This reevaluation comes after Biogen invested $1.5 billion upfront in the collaboration, with Sage set to receive up to $820 million more in potential regulatory, commercial milestones, and net sales payments.
The failure of SAGE-324 adds to a series of setbacks in developing pharmacological treatments for essential tremor, a condition that hasn't seen a new drug approval since the 1960s despite recent device authorizations by the FDA. The complexity of essential tremor biology, particularly GABA dysfunction, continues to challenge drug developers. Previous attempts by companies like Neurocrine Biosciences, Praxis Precision Medicines, and Jazz Pharmaceuticals have also met with limited success. Analysts have questioned the future of the Sage and Biogen partnership, particularly in light of the ongoing development of other joint projects such as the postpartum depression medication Zurzuvae.
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