Two-Week Oral Treatment Shows Promise in Phase 3 Major Depressive Disorder Study

The once-daily, 2-week investigational oral medication zuranolone showed a statistically significant and clinically meaningful reduction in depressive symptoms compared with the placebo in a phase 3 study of patients with major depressive disorder, drugmakers Sage Therapeutics Inc and Biogen Inc recently announced.

The double-blind WATERFALL Study randomized 543 adults with major depressive disorder to 2 weeks of nightly treatment with zuranolone (SAGE-217/BIIB125) 50 mg or placebo. At screening and baseline, patients had a 17-item Hamilton Rating Scale for Depression (HAMD-17) total score of 24 or higher.

At day 15, patients who received zuranolone had an average change of 14.1 on HAMD-17 total score, compared with -12.3 for patients who received placebo. Four weeks later, patients who responded to zuranolone on day 15 retained an average 86.1% of HAMD-17 improvement and 87.6% of Montgomery–Åsberg Depression Rating Scale improvement.

Zuranolone was generally well-tolerated and demonstrated a safety profile consistent with previous studies. Some 90.3% of patients in the zuranolone group completed the trial.

Inflammation Connected to Risk of Major Depressive Disorder

The rate of treatment-emergent adverse events was 60.1% in the zuranolone group compared with 44.6% in the placebo group. The most common treatment-emergent adverse events with zuranolone that affected 5% or more of patients included somnolence (15.3%), dizziness (13.8%), headache (10.8%), and sedation (7.5%). The portion of patients reporting treatment-emergent adverse events leading to drug discontinuation was 3.4% with zuranolone and 1.5% with placebo. Two patients in each group reported serious adverse events; no deaths occurred in the study.

“These data suggest that this treatment, if approved, has the potential to work fast with a short-course of therapy that is well-tolerated, with the effect maintained over the long-term,” said Anita H. Clayton, MD, chair of psychiatry and neurobehavioral sciences at the University of Virginia School of Medicine, Charlottesville, Virginia.

“This will empower my patients to think differently about their depression and treatment, and to rapidly return to their life. Depression is not an identity, it’s an episodic disorder that we hope in the future to be able to treat quickly with treatments that are well-tolerated and with benefits that last.”

—Jolynn Tumolo

Reference

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. News release. Sage Therapeutics, Biogen; June 15, 2021. Accessed June 22, 2021.