Page 1

Sage Therapeutics TM 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 June 15 , 2021 • At the Day 15 primary endpoint , zuranolone 50 mg showed a statistically significant and clinically meaningful reduction in depressive symptoms as measured by HAMD - 17 ( p = 0.0141 ) compared to placebo • Rapid onset of treatment effect was seen in HAMD - 17 results at Days 3 , 8 , and 12 • Patients with a response at Day 15 to zuranolone retained on average 86 % of their HAMD - 17 improvement at Day 42 ( 4 weeks after dosing ended ) • Zuranolone was generally well - tolerated and demonstrated a safety profile consistent with previous clinical studies ; trial completion rate was 90.3 % in the zuranolone group • Zuranolone is an investigational two - week , once - daily oral drug for MDD that represents a potential new class of drug for the management of this common but serious mental health disorder CAMBRIDGE , Mass .-- ( BUSINESS WIRE ) -- Jun . 15 , 2021-- Sage Therapeutics , Inc. ( Nasdaq : SAGE ) and Biogen Inc. ( Nasdaq : BIIB ) today announced that the WATERFALL Study in patients with MDD met its primary endpoint with zuranolone ( SAGE - 217 / BIIB125 ) 50 mg showing statistically significant improvement in depressive symptoms compared with placebo at Day 15 as assessed by the 17 - item Hamilton Rating Scale for Depression ( HAMD - 17 ) total score . LS means ( SE ) change from baseline in HAMD - 17 total score at Day 15 for patients who received zuranolone 50 mg was -14.1 ( 0.51 ) compared with -12.3 ( 0.50 ) for patients who received placebo ( LS mean difference -1.7 points ; p = 0.0141 ) . This press release features multimedia . View the full release here : https://www.businesswire.com/news/home/20210615005402/en/ Monoamine - based antidepressants have been the standard of care for chronic treatment of MDD for the past 60 years . They are treatments administered daily , which require sufficient exposure and continuous use to maintain effect . Zuranolone is a two - week , once - daily oral drug under investigation for the treatment of MDD . It is a molecule that is designed to potentially provide a rapid - acting , sustainable treatment option , and could represent a breakthrough in the current management of depression . The WATERFALL Study was a pivotal , Phase 3 , double - blind , randomized , placebo - controlled study evaluating the efficacy and safety of zuranolone 50 mg in adults 18 to 64 years with MDD ( N = 543 ) . The WATERFALL Study enrolled patients who had MDD with a HAMD - 17 total score ≥24 at screening and Day 1 prior to dosing . " 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 . " " 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 Alfred Sandrock , Jr. , M.D. , Ph.D. , Head of Research and Development at Biogen . " Major depressive disorder is a common co - morbidity 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 . " Zuranolone was generally well - tolerated in the WATERFALL Study and demonstrated a safety profile consistent with previous clinical studies . The rate of treatment emergent adverse events ( TEAEs ) in the zuranolone group was 60.1 % ( 161/268 ) vs the placebo group at 44.6 % ( 120/269 ) . The majority of the TEAEs were mild to moderate . The most common TEAEs that were ≥ 5 % in patients treated with zuranolone ( rates vs placebo ) included 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 % ) ; these events predominantly occurred during the 14 - day treatment period . Throughout the study , a total of two patients each ( 0.7 % ) reported serious adverse events ( SAES ) in the zuranolone and placebo groups ; no death occurred in the study . The percent of patients reporting TEAEs leading to drug discontinuation was 3.4 % ( 9/268 ) and 1.5 % ( 4/269 ) , in the zuranolone and placebo groups , respectively . No signal for withdrawal symptoms 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 ) were identified . " 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 , M.D. , Chair of Psychiatry and Neurobehavioral Sciences , 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 . ”