Sage Therapeutics and Biogen have reported that zuranolone (SAGE-217/BIIB125) met the primary goal in the Phase III WATERFALL Study in patients with major depressive disorder (MDD).
Zuranolone is an investigational neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator. It is intended for oral once-daily use for two weeks.
The double-blind, placebo-controlled Phase III WATERFALL study analysed the efficacy and safety of the drug in 543 adults aged 18 to 64 with MDD. Participants received either zuranolone 50mg or placebo.
The primary endpoint was the change in the 17-item Hamilton Rating Scale for Depression (HAM-D) total score from baseline to day 15.
Change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A) total score, among others, were the secondary goals.
Data from the trial showed that zuranolone provided a statistically significant and clinically meaningful decrease in depressive symptoms as measured by HAMD-17 versus placebo at day 15, meeting the primary goal.
LS mean difference of -1.7 points was observed between subjects receiving zuranolone and placebo.
Furthermore, subjects who experienced a response at day 15 in the zuranolone arm retained on average 86.1% of their HAMD-17 improvement at day 42, which was four weeks after dosing concluded.
Zuranolone was generally well-tolerated in this trial and its safety profile was in line with earlier reported clinical data.
Biogen Research and Development head Alfred Sandrock said: “These results represent hope and positive progress for the more than 250 million patients worldwide who are estimated to live with depression.
“We believe zuranolone has the potential to offer a unique, first-in-class therapeutic for depression with a distinct benefit-risk profile to people living with this common but serious mental health condition.”
Zuranolone is currently being analysed as a rapid-acting, two-week therapy for postpartum depression and MDD in the NEST and LANDSCAPE clinical trial programmes.
The latest development comes after Biogen’s Phase III trial of its gene therapy, timrepigene emparvovec, did not meet its primary or key secondary endpoints in patients with the rare inherited eye disease choroideremia.