The treatment was well-tolerated with a safety profile consistent with previous clinical trials.
New data shows zuranolone (SAGE-217/BIIB125) 50 mg provided statistically significant improvement in depressive symptoms compared to placebo at day 15 in patients with major depressive disorder (MDD).
Stakeholders from Sage Therapeutics and Biogen announced the positive results from the phase 3, double-blind, randomized, placebo-controlled WATERFALL study showing the treatment met the predetermined primary endpoint, assessed by the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score.
The LS mean changes from baseline in HAMD-17 total score at day 15 for patients treated with zuranolone 50 mg was -14.1, compared to the placebo group with an LS mean score of -12.3 (LS mean difference, -1.7 points; P = 0.0141).
In the WATERFALL study, the researchers evaluated the efficacy and safety of the drug in 543 adults with MDD aged 18-64 years old. Each patient enrolled in the study had a HAMD-17 total score of at least 24 at screening and day 1 prior to dosing.
For the past 6 decades, clinicians have mainly relayed on monoamine-based antidepressants to treat chronic MDD. This class of treatment is administered daily and require sufficient exposure and continuous use to maintain effect. However, the new treatment is a two-week, once-daily oral drug with a molecule designed to provide a rapid-acting, sustainable treatment option.
The safety analysis shows the treatment was generally well-tolerated and exhibited a safety profile consistent with previous clinical trials.
A total of 161 patients (60.1%) in the treatment cohort experienced a treatment emergent adverse event, compared to 120 patients (44.6%) in the placebo group. However, the majority of these adverse events were considered mild to moderate, with the most common events being somnolence 15.3% (vs 3.0%), dizziness 13.8% (vs 2.2%), headache 10.8% (vs 7.8%), and sedation 7.5% (vs 0.4%).
The majority of these events occurred during the 14-day treatment period.
In addition, 2 patients in both the placebo group and the zuranolone group experienced a serious adverse event, while no deaths occurred in either study group. Nine (3.4%) patients reported a treatment emergent adverse event that led to drug discontinuation in the treatment arm, compared to 4 patients (1.5%) in the placebo group.
Finally, there was no signal for withdrawal symptoms identified as assessed by the 20-item Physician Withdrawal Checklist (PWC-20), or for increased suicidal ideation or behavior as per the Columbia-Suicide Severity Rating Scale (C-SSRS).
“Sage’s expertise in the modulation of the GABA receptor pathway in the brain, coupled with insights on the treatment wants and needs of clinicians and patients, has resulted in our targeting a unique benefit/risk profile with the development of zuranolone supported to date by the data generated in the WATERFALL Study and the broader Landscape and NEST programs,” said Barry Greene, Chief Executive Officer at Sage Therapeutics, in a statement.
“We dared to imagine a different future for the treatment of MDD where patients have the potential to experience a rapid response that is well-tolerated and that may enable them to stay better with long periods free from depression symptoms, and free from daily chronic treatments and related side effects.”