Phase III MOUNTAIN Study of SAGE 217 fails to meet endpoint in major depressive disorder.- Sage Therapeutics

Sage Therapeutics reported topline results from the pivotal Phase III MOUNTAIN Study evaluating the effect of SAGE 217 (zuranolone) 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. 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 SAGE-217 development program includes five other pivotal studies, two of which have reported positive data, one in MDD and one in postpartum depression (PPD), and three of which are ongoing. Post-hoc analysis revealed that in the MOUNTAIN Study, approximately 9% of patients in the SAGE-217 30 mg group had no measurable drug concentration, consistent with non-compliance in taking SAGE-217. Excluding these patients from the primary analysis set (SAGE-217 30 mg vs. placebo) resulted in statistical significance at all timepoints through, and including, Day 15 (p<0.048).>

The study enrolled more patients with an overall distribution of milder severity of symptoms than previous studies of SAGE-217. When including only patients with a HAM-D>24 (n=124 for SAGE-217 30 mg), a post-hoc analysis demonstrated statistical significance at all timepoints through, and including, Day 15 (p<0.032). analyses utilizing a ham-d cutoff of 25 or 26 were also statistically significant. sage-217 was generally well-tolerated and showed a similar safety profile as seen in earlier studies. overall reports of adverse events (aes) during the 14-day treatment period and 28-day follow-up were similar between sage-217 and placebo (30 mg 54.2%, 20 mg 50.0%, placebo 48.9%). the most common aes ( greater than 5%) in either sage-217 group were headache, dizziness, somnolence, fatigue, diarrhea, sedation and nausea.>