Biogen and Sage’s once-daily depression therapeutic has hit the primary endpoint in a pivotal phase 3 trial in patients with major depressive disorder (MDD), the companies announced today.
In the phase 3 WATERFALL study, zuranolone met the primary endpoint of significantly improving and reducing depressive symptoms compared with placebo, as assessed by the 17-item Hamilton Rating Scale for Depression (HAMD-17).
The study enrolled adults aged 18 to 64 years who had MDD with a HAMD-17 total score greater than or equal to 24 at screening and day 1 prior to dosing.
After 15 days of treatment, patients receiving zuranolone experienced an average change of -14.1 points on the HAMD-17 compared to -12.3 on placebo, a mean difference of 1.7 points.
Patients who had a response at day 15 in the zuranolone group retained 86.1% of their HAMD-17 improvement at day 42, with a similar maintenance of response also observed with the Montgomery-Åsberg Depression Rating Scale (MADRS).
Although this finding was not statistically significant, there was a ‘numerical advantage’ in favour of zuranolone demonstrated at day 42.
On the safety front, the rate of treatment emergent adverse events (TEAEs) in the zuranolone group was 60.1% compared to 44.6% in the placebo group.
The most common TEAEs in the zuranolone group included somnolence, dizziness, headache and sedation.
Over the course of the study, a total of two patients each reported serious adverse events in the zuranolone and placebo groups. The proportion of patients reporting TEAEs leading to drug discontinuation was 3.4% and 1.5% in the zuranolone and placebo groups, respectively.
“Together with our collaboration partners at Sage, we are proud to announce highly encouraging results from the phase 3 WATERFALL Study of zuranolone in major depressive disorder,” said Alfred Sandrock, Jr., head of research and development at Biogen
“These results represent hope and positive progress for the more than 250 million patients worldwide who are estimated to live with depression. Major depressive disorder is a common co-morbidity of many diseases represented in Biogen’s neuroscience portfolio,” he added.
In November 2020, Biogen signed a $3.1bn deal focused on a series of potential depression and movement disorder therapies under development by Sage.
As part of that agreement, Biogen and Sage are jointly developing and will jointly commercialise zuranolone, which – aside from major depressive disorder (MDD) – is also being studied as a potential treatment for postpartum depression and other psychiatric disorders.