Sage Therapeutics and Biogen Announce that the Phase 3 SKYLARK Study of Zuranolone in Postpartum Depression Met its Primary and All Key Secondary Endpoints

Zuranolone 50 mg demonstrated a statistically significant and clinically meaningful improvement in depressive symptoms at Day 15, the primary endpoint, and at Days 3, 28, and 45, key secondary endpoints

Zuranolone 50 mg was generally well-tolerated and demonstrated a safety profile consistent with prior studies

Postpartum depression is one of the most common medical complications during and after pregnancy impacting approximately 1 in 8 women annually in the U.S.

CAMBRIDGE, MA, USA I June 1, 2022 I Biogen Inc. (Nasdaq: BIIB) and Sage Therapeutics, Inc. (Nasdaq: SAGE) today announced that the Phase 3 SKYLARK Study of zuranolone, an investigational oral drug being evaluated in women with postpartum depression (PPD), met its primary and all key secondary endpoints. Women treated with zuranolone 50 mg (n=98) demonstrated 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. The least-squares (LS) mean (SE) CFB in HAMD-17 total score at Day 15 for women who received zuranolone 50 mg was -15.6 (0.82) compared with -11.6 (0.82) for women who received placebo (LS mean difference -4.0 points; p=0.0007).

“Reducing suffering from postpartum depression as rapidly and effectively as possible to restore maternal mental health is of the utmost importance for moms and their babies,” said Dr. Kristina Deligiannidis, principal investigator of the SKYLARK Study and Associate Professor, the Feinstein Institutes for Medical Research in Manhasset, New York. “These encouraging results are another important step in efforts to develop a novel treatment option for patients who suffer from this prevalent condition.”

The study met all key secondary endpoints with rapid and statistically significant improvement in depressive symptoms as early as Day 3 for participants treated with zuranolone 50 mg compared to placebo, which was sustained at all measured timepoints through Day 45 as measured by CFB in HAMD-17 total score.

SKYLARK Study Summary Results

*Key Secondary Endpoint

In addition, the study demonstrated statistically significant improvement in the key secondary endpoint of change from baseline in the Clinical Global Impression Severity (CGI-S) scale at Day 15 for participants treated with zuranolone 50 mg as compared to placebo (zuranolone -2.2 vs. placebo -1.6, p= 0.0052). The CGI-S is a clinician-administered 7-point scale that rates the severity of a person’s disease at the time of assessment. 

Zuranolone is an investigational two-week, once-daily oral drug being developed for major depressive disorder (MDD) and PPD. The SKYLARK Study in PPD was a randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of zuranolone 50 mg dosed once daily for 14 days compared to placebo. Women enrolled in the study (n=200) had a total score of equal to or greater than 26 at baseline in the HAMD-17 and were followed for up to 45 days. The study population included approximately 22% Black or African American women and 38% Hispanic or Latina women.

Zuranolone 50 mg was generally well-tolerated and demonstrated a safety profile consistent with that observed in the clinical development program to date. In women in both treatment groups who experienced treatment emergent adverse events (TEAEs), the majority were mild to moderate in severity. The most common TEAEs (>5% in the zuranolone 50 mg arm) were somnolence, dizziness, sedation, headache, diarrhea, nausea, urinary tract infection and COVID-19. No evidence of withdrawal symptoms or increased suicidal ideation or behavior were identified as assessed by the 20 item Physician Withdrawal Checklist and the Columbia Suicide Severity Rating Scale, respectively.  

“The positive outcomes of the SKYLARK Study are a critical step in our mission to help women suffering with postpartum depression find rapid relief from their depressive symptoms so they can get back to feeling like themselves,” said Barry Greene, Chief Executive Officer at Sage. “Postpartum depression can be devastating for women and their families. If approved, zuranolone would be the first oral medication specifically indicated to treat PPD.”

“Postpartum depression is frequently under-recognized, and it can take time for women to be clinically diagnosed and treated,” said Katherine Dawson, M.D., Head of the Therapeutics Development Unit at Biogen. “Our hope is to be able to offer an innovative treatment option to potentially reduce the overwhelming impact postpartum depression can have on women and their families.”

PPD is one of the most common medical complications during and after pregnancy¹ and is estimated to affect approximately one in eight women who have given birth in the U.S. or approximately 500,000 women annually.²  Symptoms of PPD can include depressed mood, loss of interest in activities, changes in sleep patterns and appetite, decreased energy, feelings of guilt or worthlessness, trouble concentrating and in some cases thoughts of suicide.³ While recognized by the U.S. Department of Health and Human Services as a high-priority public health issue, screening rates vary and nearly 70% of women with PPD may go undiagnosed.¹

“Every day we hear about the devastating consequences PPD and other perinatal mood disorders have on women and their families,” said Wendy N. Davis, PhD, PMH-C, Executive Director, Postpartum Support International. “Access to treatment for women with PPD is still very low, and promising new medicines that have the potential to work quickly and specifically could provide an additional option that is desperately needed.”

The NEST clinical development program for zuranolone in PPD includes the SKYLARK and ROBIN Studies. The first study in the NEST program, the Phase 3 ROBIN Study, also met its primary endpoint. The ROBIN Study was a multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and pharmacokinetics of zuranolone 30 mg in the treatment of PPD. The LANDSCAPE and NEST development program for zuranolone includes 7 clinical studies evaluating the safety and efficacy of zuranolone in MDD and PPD.

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 plan to complete the MDD NDA filing in the second half of 2022. An associated NDA filing for PPD is anticipated in early 2023.

Conference Call Information
Sage will host a conference call and webcast on June 1 at 8:00 a.m. ET to review the totality of the SKYLARK Study. The live webcast can be accessed on the investor page of Sage’s website at investor.sagerx.com. A replay of the webcast will be available on Sage’s website approximately two hours after the completion of the event and will be archived for up to 30 days.

About the SKYLARK Study
The SKYLARK Study (217-PPD-301) was a Phase 3, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of zuranolone 50 mg compared to placebo in adult women with severe PPD. The 200 patients enrolled in the study were randomized to receive zuranolone 50 mg or a placebo once nightly for 14 days. People in the study were then followed for an additional four weeks. The primary endpoint was the change from baseline in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score at Day 15. The companies anticipate further data disclosures at upcoming meetings and publications. For more information about this trial, please visit clinicaltrials.gov.

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, two-week, investigational drug in development for the treatment of major depressive disorder (MDD) and postpartum depression (PPD). Zuranolone is an investigational 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.

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. For more information, please visit www.sagerx.com.

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.

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References

1. “ACOG Committee Opinion No. 757: Screening for Perinatal Depression.” Obstetrics and gynecology vol. 132,5 (2018): e208-e212. doi:10.1097/AOG.0000000000002927
2. Bauman BL, et al. Morbidity and Mortality Weekly Report, 2020;69(19):575-581
3. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596

SOURCE: Sage Therapeutics