Sage Therapeutics and Biogen Present Further Analyses from Phase 3 SKYLARK Study of Zuranolone in Postpartum Depression at the European College of Neuropsychopharmacology (ECNP) Congress

• Zuranolone 50 mg demonstrated a clinically meaningful and statistically significant improvement in depressive symptoms at Day 15, the primary endpoint, and at Days 3, 28, and 45, key secondary endpoints as previously reported
• Newly presented data offered additional insight into the SKYLARK Study and further demonstrated the rapid improvements in depressive symptoms observed in the clinical trial
• Zuranolone was generally well-tolerated, with a safety profile consistent with previous clinical trials; most treatment-emergent adverse events (TEAEs) were mild or moderate in severity in the SKYLARK Study

Sage Therapeutics, Inc. (Nasdaq: SAGE) and Biogen Inc. (Nasdaq: BIIB) today presented additional data from the Phase 3 SKYLARK Study of zuranolone in adult women with postpartum depression (PPD), at the 35th European College of Neuropsychopharmacology (ECNP) Congress, taking place October 15-18, 2022, in Vienna, Austria. This was the first time the SKYLARK Study was presented at a medical congress. Zuranolone is an investigational therapy being evaluated as a once-daily, 14-day oral short course treatment in adults with major depressive disorder (MDD) and PPD.

The SKYLARK Study, as previously reported, achieved the primary and all key secondary endpoints, with study participants demonstrating rapid and significant improvements in depressive symptoms as early as Day 3 that were sustained through Day 45. Women with PPD who were treated with zuranolone 50 mg (n=98) showed a statistically significant and clinically meaningful improvement in depressive symptoms at Day 15, the primary endpoint, compared to placebo (n=97) as measured by a change from baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score (least-squares mean ±SE: zuranolone 50 mg −15.6 ±0.82 vs. placebo −11.6 ±0.82; [p=0.0007]). The study population was diverse, including approximately 22% Black or African American women and 38% identifying ethnically as Hispanic or Latina women.

In the presentation at ECNP, additional secondary endpoint data demonstrated that a higher proportion of patients in the zuranolone 50 mg arm achieved a HAMD-17 response (≥ 50% decrease from baseline HAMD-17 total score) as compared with the placebo arm at Days 3, 8, 15, 21, and 28 (p less than 0.05, at all time points). Data also showed that a higher proportion of patients in the zuranolone arm achieved HAMD-17 remission (HAMD-17 total score ≤ 7) than in the placebo arm from Day 3 through Day 45 (Day 45 pless than 0.05).

“The results of the SKYLARK Study are incredibly encouraging and show the potential positive impact zuranolone could have for women with PPD. Rapid symptom relief is critical for women with PPD, because delays in treatment efficacy can negatively impact resolving depressive symptoms and overall clinical outcomes for mother and baby,” said Dr. Kristina Deligiannidis, Principal Investigator of the study and Professor, the Feinstein Institutes for Medical Research in Manhasset, New York. “I’ve seen the consequences PPD can have on a mother’s ability to care for herself, her baby, and her family in a way that can have a generational impact. There are currently no oral therapies approved for PPD and we desperately need new treatment options to help women get well as soon as possible and stay well.”

Additional secondary endpoints showed further evidence of the potential impact of zuranolone on the reduction of other PPD related symptoms, including anxiety in these patients. Treatment with zuranolone was shown to significantly improve symptoms of anxiety at Days 3, 8, 15, and 45 (p less than 0.05, at all time points) when compared to placebo as measured by the Hamilton Anxiety Rating Scale (HAM-A).

In the SKYLARK Study, zuranolone was generally well-tolerated, with a safety profile consistent with that observed in the clinical development program to date. The majority of treatment-emergent adverse events (TEAEs) experienced by women in both treatment groups were mild to moderate in severity. A total of two participants (all in the zuranolone group) experienced four serious adverse events all of which were assessed by the investigator as unrelated to the therapy. Common TEAEs (>5% in the zuranolone 50 mg arm) were somnolence, dizziness, sedation, headache, diarrhea, nausea, urinary tract infection and COVID-19.

Sage Therapeutics and Biogen have initiated a rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration for zuranolone in the treatment of MDD and PPD, and plan to complete the NDA filing in the second half of 2022.

About Postpartum Depression (PPD)
Postpartum depression (PPD) is one of the most common medical complications during and after pregnancy.¹ PPD can have a serious negative impact on a woman, including significant functional impairment, depressed mood and/or loss of interest in her newborn, and associated symptoms of depression such as loss of appetite, difficulty sleeping, motor challenges, lack of concentration, loss of energy and poor self-esteem. PPD is estimated to affect approximately one in eight women who have given birth in the U.S. or approximately 500,000 women annually.²

About Zuranolone
Zuranolone (SAGE-217/BIIB125) is a once-daily, 14-day, investigational drug in development for the treatment of major depressive disorder (MDD) and postpartum depression (PPD). Zuranolone is an oral neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). The GABA system is the major inhibitory signaling pathway of the brain and central nervous system and contributes to regulating brain function. Zuranolone has been granted Fast Track and Breakthrough Therapy Designation for MDD and Fast Track Designation for PPD by the U.S. Food & Drug Administration.

Zuranolone is being evaluated in the LANDSCAPE and NEST clinical development programs. The two development programs include multiple studies examining use of zuranolone in several thousand people with a variety of dosing, clinical endpoints, and treatment paradigms. The LANDSCAPE program includes five studies of zuranolone in people with MDD (MDD-201B, MOUNTAIN, SHORELINE, WATERFALL, and CORAL Studies). The NEST program includes two placebo-controlled studies of zuranolone in women with PPD (ROBIN and SKYLARK Studies). Additionally, Shionogi completed a Phase 2 study of zuranolone in Japan in people with MDD.

Sage Therapeutics and Biogen have initiated a rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration for zuranolone in the treatment of MDD and PPD, and plan to complete the NDA filing in the second half of 2022. If approved, zuranolone would be the first oral medication specifically indicated to treat PPD.

About Sage Therapeutics
Sage Therapeutics is a biopharmaceutical company fearlessly leading the way to create a world with better brain health. Our mission is to pioneer solutions to deliver life-changing brain health medicines, so every person can thrive.

About Biogen
As pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has a leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and developed the first and only approved treatment to address a defining pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and focusing on advancing one of the industry’s most diversified pipeline in neuroscience that will transform the standard of care for patients in several areas of high unmet need.

In 2020, Biogen launched a bold 20-year, $250 million initiative to address the deeply interrelated issues of climate, health, and equity. Healthy Climate, Healthy Lives™ aims to eliminate fossil fuels across the company’s operations, build collaborations with renowned institutions to advance the science to improve human health outcomes, and support underserved communities.