“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. These results represent hope and positive progress for the more than 250 million patients worldwide who are estimated to live with depression,” said Head of Research and Development at Biogen, Alfred Sandrock, Jr, MD, PhD. “Major depressive disorder is a common comorbidity of many diseases represented in Biogen’s neuroscience portfolio. 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.”1
Zuranolone is a two-week, once-daily oral drug under investigation for the treatment of MDD and postpartum depression designed to potentially provide a rapid-acting, sustainable treatment option. It is an investigational, oral, neuroactive steroid GABA-A receptor positive allosteric modulator. Zuranolone has been granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA).2
“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. “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. In doing so, we aspire to help eliminate stigma associated with brain health disorders so that we can move beyond brain health awareness to brain health action.”1
The WATERFALL Study was a phase 3, double-blind, randomized, placebo-controlled study that evaluated the efficacy and safety of zuranolone 50 mg in adults aged 18 to 64 years with MDD. The study enrolled 543 patients with MDD, who received either 50 mg of zuranolone or placebo once nightly for 14 days. The study’s primary endpoint was to change from baseline in the17-item Hamilton Rating Scale for Depression (HAM-D) total score by day 15. The patients who responded by day 15 retained on average 86.1% of their HAMD-17 improvement 4 weeks later.
Zuranolone was generally well-tolerated in the WATERFALL Study, and the safety profile was consistent with previous clinical studies. The rate of treatment emergent adverse events in the zuranolone group was 60.1% vs the placebo group at 44.6%. The majority of the treatment emergent adverse events were mild to moderate and included somnolence (15.3%), dizziness (13.8%), headache (10.8%), and sedation 7.5%. The events happened primarily during the 14-day treatment period.
“I’m really excited about these breakthrough data: we know MDD is episodic and zuranolone has the potential to treat episodically. The LANDSCAPE clinical studies are all helpful taken together because they provide data on both short- and long-term use of zuranolone,” said Anita H. Clayton, MD, Chair of Psychiatry and Neurobehavioral Sciences at the University of Virginia School of Medicine. “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. 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.”1
In terms of the future, Sage and Biogen intend to discuss next steps with the FDA, as well as present the full data from The WATERFALL Study at conventions and forums.
“MDD is a pressing mental health concern and, unlike physical health concerns where innovation is commonplace, many of the treatments for MDD were first approved more than two decades ago,” said Paul Gionfriddo, President and CEO of Mental Health America (MHA). “We welcome today’s news, and the potential for a new and innovative treatment that could change the way we treat depression.”1
References
1. Sage Therapeutics. 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. June 15, 2021. https://investor.sagerx.com/news-releases/news-release-details/sage-therapeutics-and-biogen-announce-positive-pivotal-phase-3
2. Kuntz L. Anticipated phase 3 interim results for Sage’s depression treatment, zuranolone. Psychiatric Times. October 15, 2020. https://www.psychiatrictimes.com/view/anticipated-phase-3-interim-results-for-sage-s-depression-treatment-zuranalone