Recently announced topline results from a Phase II study show SAGE-324, Sage Therapeutics’ investigational oral neuroactive steroid GABAA receptor positive allosteric modulator, significantly reduced tremor score in adult patients with essential tremor.
SAGE-324 performing well in movement disorder patients. (PictureDesignSwiss/Shutterstock)
Recently announced topline results from a Phase II study show SAGE-324, Sage Therapeutics’ investigational oral neuroactive steroid GABAA receptor positive allosteric modulator, significantly reduced tremor score in adult patients with essential tremor.
SAGE-324 binds to synaptic and extrasynaptic GABAA receptors, which subsequently enhances inhibitory activity of the GABAergic system, the brain’s major inhibitory neurotransmission system.
In November of last year, Sage and Biogen entered into a global collaboration agreement to develop and commercialize the therapy in essential tremor and other neurological indications. Under the deal, Biogen provided Sage an upfront payment of $1.52 billion to develop and commercialize SAGE-324, in addition to zuranolone for major depressive disorder, postpartum depression (PPD) and other psychiatric disorders.
The new topline findings announced by Sage and Biogen come from the multicenter KINETIC study, which included patients between 18 and 80 years of age with essential tremor, a common movement disorder that affects approximately 6.4 million people in the United States.
“There is an extraordinary unmet need for people suffering with essential tremor, a condition that can cause significant disability in patients,” according to a statement made by Dr. Rodger Elble, M.Da neurologist at the Southern Illinois University School of Medicine. “The only approved medicine was developed more than 50 years ago, and most medicines used for ET were developed for other conditions, and their benefits to people with ET were only discovered serendipitously. Current investigational drugs like SAGE-324, if successful, may offer potential for new treatment options for tremor management, as more than 50% of people with ET do not respond optimally to the current standard of care.”
In the KINETIC study, researchers assessed the therapy’s efficacy, safety and tolerability when administered at 60 mg. The primary endpoint of this placebo-controlled trial was the change in the upper limb tremor score, measured by Item 4 of The Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale, from baseline to day 29.
In the full analysis set (n=67), the study met the primary endpoint, showing treatment with SAGE-324 significantly reduced the TETRAS by day 29 compared with placebo (p=0.049). Overall, treatment with SAGE-324 in this study was associated with a 36% reduction in the score from baseline when compared with treatment with placebo.
Participants with a more severe tremor at baseline also achieved a statistically significant reduction in their TETRAS Performance Subscale Item 4 upper limb tremor score if they received SAGE-324 versus placebo (p=0.007). This subpopulation experienced a 41% reduction from baseline in this score, while those who received placebo only experienced an 18% reduction.
“The strong correlation observed in this study between TETRAS performance scale – measuring reduction of upper limb tremor, a disabling symptom experienced by more than 90% of people suffering from essential tremor -- and improvement on the ADL score provides suggestive evidence that these findings have the potential to be truly impactful for people with essential tremor,” said Sage Therapeutics Chief Executive Officer Barry Greene. “We believe the data announced today provide clear support and insights for the continued development of SAGE-324 in an area of significant unmet medical need.”
Biogen’s Head of Research and Development, Alfred Sandrock, Jr., M.D., Ph.D., added that he and his team are encouraged by the KINETIC results, given the unmet needs involved in the disorder.
“For people with essential tremor, uncontrollable shaking of the hands, head, voice, or legs can create difficulty eating, dressing, writing, and pursuing other day-to-day tasks,” Sandrock said. “It is our hope that, in collaboration with Sage, we will be able to deliver an innovative and meaningful new treatment option for these patients.”
