Sage Therapeutics, a clinical-stage biopharmaceutical company developing novel medicines to treat life-altering central nervous system (CNS) disorders, announced positive top-line results from the Phase 2, double-blind, placebo-controlled clinical trial of SAGE-217 in the treatment of 89 adult patients with moderate to severe major depressive disorder (MDD). In the trial, treatment for 14 days with SAGE-217 was associated with a statistically significant mean reduction in the Hamilton Rating Scale for Depression (HAM-D) 17-Item total score from baseline to Day 15 (the time of the primary endpoint) of 17.6 points for SAGE-217, compared to 10.7 for placebo (p<0.0001). Statistically significant improvements were observed in the HAM-D compared to placebo by the morning following the first dose through Week 4 and the effects of SAGE-217 remained numerically greater than placebo through the end of follow-up at Week 6. At Day 15, 64 percent of patients who received SAGE-217 achieved remission, defined as a score of 7 or less on the HAM-D scale, compared with 23 percent of patients who received placebo (p=0.0005). Other secondary endpoints were all similarly highly significant at Day 15 (p≤0.002).
SAGE-217 was generally well-tolerated with no serious or severe adverse events; the most common adverse events (AEs) in the SAGE-217 group were headache, dizziness, nausea, and somnolence. A low rate of discontinuations due to AEs was reported; overall reports of AEs were similar between drug (53%) and placebo (46%), with a safety profile consistent with that seen in earlier trials. SAGE-217 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) in May 2017.
“These very encouraging data suggest the potential of SAGE-217 in the treatment of MDD as well as other mood-related disorders that we may pursue,” said Jeff Jonas M.D., chief executive officer of Sage Therapeutics. “There has been little innovation in the discovery and development of treatments for depression in the last two decades. Coupled with our recent positive Phase 3 data read-out evaluating brexanolone for the treatment of postpartum depression, the findings in this study suggest our pipeline of proprietary GABAA modulators may impact novel and fundamental brain mechanisms, offering potential development opportunities in a variety of indications. The positive activity and safety findings of SAGE-217 in MDD support advancing the program into later stage clinical development and we will work with the FDA to determine next steps in the further development of SAGE-217.”
The GABA system is the major inhibitory signaling pathway of the central nervous system (CNS), and contributes significantly to regulating CNS function. SAGE-217 is a novel, highly potent and selective, next generation GABAA receptor positive allosteric modulator that is being developed as a once-daily, oral therapy for the treatment of various CNS disorders. SAGE-217 was discovered by Sage, and the Company maintains worldwide rights to the compound.
“There are currently significant gaps in the disease management of depression and our development goal at Sage is to change patients’ expectations by transforming the treatment landscape for MDD,” said Steve Kanes, M.D., Ph.D., chief medical officer of Sage Therapeutics. “If successfully developed, SAGE-217 has the potential to offer the first truly new mechanism of action in the pharmacologic treatment of depression in more than 20 years. If the results from this trial are replicated in Phase 3 trials, SAGE-217 may meet the needs of patients with MDD for a once-daily oral treatment that potentially provides a rapid, well-tolerated and durable response with a high rate of remission.”
Filed Under: Drug Discovery