Sage Therapeutics reported topline results from the pivotal Phase 3 MOUNTAIN Study evaluating the effect of SAGE-217 on depressive symptoms in adults with major depressive disorder (MDD). The MOUNTAIN Study did not meet its primary endpoint of a statistically significant reduction from baseline compared to placebo in the 17-item Hamilton Rating Scale for Depression (HAM-D) total score at Day 15.
MOUNTAIN was a double-blind, placebo-controlled pivotal study and enrolled 581 adults with major depressive disorder (MDD). The patients were randomized to receive SAGE-217, 20 mg or 30 mg, or placebo, once-nightly for two-weeks. The primary endpoint of the study is the change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) total score at Day 15. SAGE-217 30 mg, given once-daily as an oral treatment, was associated with a mean reduction of 12.6 in HAM-D total score compared to 11.2 for placebo (p=0.115). Patients in the SAGE-217 30 mg group achieved statistically significant reductions in the HAM-D total score at Days 3, 8 and 12 (p<0.018 for each timepoint). The most common AEs (≥5%) in either SAGE-217 group were headache, dizziness, somnolence, fatigue, diarrhea, sedation and nausea.
According to Steve Kanes, M.D., Ph.D., chief medical officer at Sage. “As a designated breakthrough therapy, we are evaluating the path forward to more fully inform a potentially expedited pathway to approval, and any amendments we might consider to the ongoing SAGE-217 pivotal program.”
SAGE-217 is an oral neuroactive steroid (NAS) GABAA receptor positive allosteric modulator (PAM). The GABA system is the major inhibitory signaling pathway of the brain and central nervous system (CNS), and contributes significantly to regulating CNS function.
The clinical program evaluating SAGE-217 in depression is progressing. To date, two positive pivotal studies have been completed, one in MDD (MDD-201) and one in postpartum depression (ROBIN Study). Ongoing studies include the REDWOOD, SHORELINE and RAINFOREST studies.
About Major Depressive Disorder
Major depressive disorder (MDD), commonly referred to as depression, is a brain health disorder that affects an estimated 17 million adults in the U.S. each year. It is one of the largest contributors to disability in the U.S. and worldwide and is characterized by symptoms of depressed mood and/or loss of interest in pleasurable activities. MDD causes significant impairment in daily life and can limit a person’s ability to fulfill work, school, family, or social responsibilities; enjoy leisure activities; or maintain health and hygiene. While antidepressants are widely used to treat MDD, large-scale studies have demonstrated that there is an unmet need in the treatment of MDD as well as the need for new therapeutic options.