Treatment with SAGE-217 (Sage Therapeutics) led to significant improvements on a depression rating scale and remission among 64% of patients with major depressive disorder (MDD) at day 15, according to phase 2 data released by the company.
“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,” said Steve Kanes, MD, PhD, Sage’s chief medical officer. “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.”
Sage announced positive top-line results from the double-blind, placebo-controlled clinical trial of SAGE-217 in the treatment of 89 adults with moderate to severe 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% of patients who received SAGE-217 achieved remission, defined as a score of 7 or less on the HAM-D scale, compared with 23% of patients who received placebo (P = 0.0005).
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 FDA in May 2017.
The positive findings support moving SAGE-217 into later stage clinical development, the company said.
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 central nervous system disorders.
Source: Sage Therapeutics; December 7, 2017.