Positive results were announced from a phase 3 study evaluating zuranolone (SAGE-217/BIIB125) for the treatment of adults with major depressive disorder (MDD).
Zuranolone is an investigational oral neuroactive steroid GABA-A receptor positive allosteric modulator that is administered once daily for 2 weeks. The double-blind, randomized, placebo-controlled WATERFALL study (ClinicalTrials.gov Identifier: NCT04442490) included 543 adults 18 to 64 years of age with MDD.
Patients were randomly assigned to receive either zuranolone 50mg or placebo once daily for 14 days. The primary endpoint was the change from baseline in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score at day 15. Key secondary endpoints included the change from baseline to day 15 in the Montgomery-Åsberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HAM-A) total score, and the Clinical Global Impression-Improvement (CGI-I) Response.
Results showed that at day 15, patients in the zuranolone treatment arm demonstrated a statistically significant and clinically meaningful improvement in depressive symptoms as measured by HAMD-17 total score (LS mean difference, -1.7 points; P =.0141). Patients with a response at day 15 retained on average 86% of their HAMD-17 improvement at day 42 (4 weeks after dosing ended).
Zuranolone was also associated with significant improvements in key secondary endpoints including MADRS (LS mean difference, -2.4; P =.0238), HAM-A (LS mean difference, -1.4; P =.0199), and CGI-I response (odds ratio, 1.5; P =.0191).
The most common treatment emergent adverse events observed in patients treated with zuranolone compared with placebo included somnolence (15.3% vs 3%), dizziness (13.8% vs 2.2%), headache (10.8% vs 7.8%), and sedation (7.5% vs 0.4%). There were no signals for withdrawal symptoms or for increased suicidal ideation or behavior.
Additional data from the WATERFALL study will be presented at a future medical meeting.
Sage Therapeutics and Biogen announce positive pivotal phase 3 results for zuranolone, an investigational two-week, once-daily therapeutic being evaluated for major depressive disorder. [press release]. Cambridge, MA: Sage Therapeutics, Inc and Biogen Inc.; June 15, 2021.