Biogen and Sage Therapeutics’ investigational neuroactive steroid did not significantly improve upper limb tremors in patients with essential tremor, the companies announced Wednesday.
Biogen and Sage Therapeutics on Wednesday announced their decision to discontinue the Phase II KINETIC 2 study in essential tremor after their investigational neuroactive steroid BIIB124 failed to meet its primary efficacy endpoint.
At day 91, BIIB124—also known as SAGE-324—failed to elicit a significant dose-response improvement in upper limb tremors, as assessed by scores in the fourth item of The Essential Tremor Rating Assessment Scale (TETRAS). Patients treated with the candidate also did not appear to see significant improvements in activities of daily living.
By contrast, BIIB124 did show a dose-relationship effect on the incidence of central nervous system depressant treatment-emergent adverse events. There was also a dose effect on the number of study dropouts due to toxicities.
The companies did not provide specific data in their announcement but said that because of these disappointing findings, they have elected to “close” the ongoing open-label safety analysis of BIIB124 in essential tremor (ET). Sage and Biogen will also no longer develop the candidate in this indication.
However, the partners have yet to completely close their doors on BIIB124 and are currently “evaluating next steps, if any,” for the development of the candidate in other indications, according to their announcement.
Sage CMO Laura Gault in a statement said that the companies are “disappointed” by the results of KINETIC 2, which “do not support further development of SAGE-324 in ET.” Katherine Dawson, head of Biogen’s therapeutic development Unit, said that the partners “believe that the finings add to the collective understanding of this debilitating condition and may help inform the field on potential future research and therapeutic approaches.”
Designed to be orally available, BIIB124 is a neuroactive steroid that works by binding to both the synaptic and extrasynaptic GABAA receptors, boosting the activity of the GABAergic system which is the brain’s major inhibitory neurotransmission system. This mechanism of action could potentially allow BIIB124 to rebalance dysregulated levels of GABA in the central nervous system, which has been implicated in various neurological conditions including ET.
BIIB124 was originally developed by Sage. In November 2020, Biogen paid $1.525 billion upfront in cash and equity investment, while pledging up to $1.6 billion in potential milestones, to gain access to several of Sage’s candidates. The centerpiece of the deal was the oral pill zuranolone, which won the FDA’s approval in August 2023 for postpartum depression but failed to nab the larger major depressive disorder indication. The drug is now marketed as Zurzuvae.
