Sage Therapeutics, a clinical-stage biopharmaceutical company developing novel medicines to treat life-altering central nervous system (CNS) disorders, announced encouraging top-line results from its Phase 2 clinical trial of orally-administered SAGE-217 for the treatment of major depressive disorder (MDD). The primary endpoint of the 13 patient Part A open-label trial was to evaluate safety and tolerability. SAGE-217 was found to be generally well-tolerated with no serious adverse events or discontinuations reported. The trial also examined the effect of SAGE-217 on the Hamilton Rating Scale for Depression (HAM-D) total score, in addition to other secondary measures. Patients in the trial had a mean HAM-D total score of 27.2 at baseline. Data demonstrated a mean reduction from baseline in the HAM-D of 19.9 points at Day 15, with 85% (11 of 13) patients showing at least a 50% reduction of their HAM-D and 62% (8 of 13) of patients achieving remission, as determined by a HAM-D ≤7. Statistically significant mean change from baseline was observed by Day 2 of the study, following the first of once-daily, nighttime oral dosing of 30 mg of SAGE-217. A significant mean change from baseline was maintained throughout the treatment period (p < 0.0001 at Day 15). The reduction from baseline in depression ratings seen in Part A of the trial met the company’s criteria for advancing SAGE-217 into a planned double-blind, placebo-controlled study (Part B).
“Understanding the caveats associated with open-label data, we are highly encouraged by the strong signal we achieved in this study, which met our internal criteria for achieving a positive signal and thus supported our plan to proceed to the double-blind, placebo-controlled part of the Phase 2 trial,” said Jeff Jonas, M.D., Chief Executive Officer of Sage. “These initial results in MDD were achieved utilizing our data-driven approach to CNS drug development – employing efficient human proof-of-concept studies to both uncover activity signals and help understand future trial methodology, before investing in larger clinical programs.”
“Our novel, orally-administered molecule, SAGE-217, was designed to reproduce the important GABA-related pharmacology of our intravenous agent SAGE-547, and is an example of our translational approach to drug development. The positive results from this clinical trial, along with the outcomes observed with SAGE-547 in postpartum depression, further validate studying this mechanism as a potential broad therapy for the treatment of mood disorders,” said Steve Kanes, M.D., Ph.D., Chief Medical Officer of Sage. “SAGE-217 has the potential to be a rapid-acting, once-daily oral therapy for MDD, with a novel mechanism of action.”
The major depressive disorder program is a two-part Phase 2 clinical trial evaluating the safety, tolerability, pharmacokinetics and efficacy of SAGE-217 in moderate to severe MDD patients. Part A of the Phase 2 trial was an open-label study evaluating SAGE-217 in 13 patients. The primary endpoint for the Part A study was to evaluate the safety and tolerability of SAGE-217. The secondary endpoint was to evaluate the effect of SAGE-217 compared to baseline following two weeks of once-daily treatment as measured by the HAM-D total score. The Part B phase of the trial will be a randomized, double-blind, parallel-group, placebo-controlled study evaluating SAGE-217 as a treatment for MDD. The design of this study will be finalized after analyses of the Part A data set are complete.
Filed Under: Drug Discovery