Zuranolone found effective for postpartum depression in phase 3 study

CAMBRIDGE, Mass: 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.

*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.