CAMBRIDGE, Mass. – December 1, 2021 -- Sage Therapeutics, Inc. (Nasdaq: SAGE), and Biogen Inc. (Nasdaq: BIIB) today announced 12-month data for the cohort of patients (n=199), who received zuranolone 50 mg once nightly for 14-days as their initial dose in the ongoing Phase 3 open-label SHORELINE Study and had the opportunity to be followed for 12-months. The SHORELINE Study, part of the LANDSCAPE clinical program, was designed to naturalistically follow adult patients with major depressive disorder (MDD) and evaluate the safety and tolerability of zuranolone as well as the need for repeat dosing for up to one year. For the primary endpoint of safety and tolerability, the data analyzed to date show zuranolone was generally well-tolerated, with no new safety findings or trends identified in the long-term safety data available regardless of the number of courses of zuranolone a patient received. Zuranolone has consistently demonstrated rapid and sustained improvements in depressive symptoms and a well-tolerated safety profile throughout the LANDSCAPE clinical program.

Secondary endpoints included the percentage of patients who received repeat dosing with zuranolone as well as response and remission as evaluated by the 17-item Hamilton Rating Scale for Depression (HAMD-17). In the zuranolone 50 mg cohort, nearly 75% of patients responded to the initial 2-week treatment course. Of those who responded to the initial course and continued in the study, approximately 80% of those patients received at most one additional zuranolone treatment during their time in the study.

The SHORELINE Study, with nearly 1,000 patients enrolled to date, is comprised of multiple cohorts, including a completed cohort with zuranolone 30 mg as a starting dose (data previously reported in 2020 and earlier in 2021) and an ongoing cohort with zuranolone 50 mg as a starting dose; both cohorts are administered zuranolone once nightly for 14 days. Enrollment of an anticipated 300 additional patients in the 50 mg cohort is ongoing. The study provides real-world insight into the potential use of zuranolone, if approved, as an as-needed treatment for MDD and builds on the data assembled in the LANDSCAPE clinical program to date. Data from the LANDSCAPE clinical program has been presented at numerous medical and scientific conferences and the Companies plan to present additional data from the ongoing SHORELINE Study in future scientific forums.

“We believe zuranolone has the potential to offer an innovative treatment approach that may enable patients with MDD to experience reductions in depressive symptoms quickly, achieve related improvements in functioning and well-being, and maintain long treatment free intervals without the types of burdensome side effects that are often associated with discontinuation of standard of care antidepressants. The SHORELINE Study helps provide important information on how zuranolone, if approved, could be used to treat people with MDD,” said Barry Greene, Chief Executive Officer at Sage Therapeutics. “We are pleased by the progress made with zuranolone throughout 2021 and the data we have generated in clinical development to date supports our belief in the overall profile of zuranolone, and its potential to make a profound difference in the lives of many patients living with MDD.”

“In the SHORELINE Study, zuranolone was generally well-tolerated by participants regardless of the number of treatment courses received during the one-year study,” said Priya Singhal, M.D., M.P.H., Head of Global Safety and Regulatory Sciences and Interim Head of R&D at Biogen. “These new data further reinforce positive findings from multiple late-stage studies of zuranolone and underscore the potential of zuranolone as a well-tolerated, rapid-acting and durable treatment option for depression.”

Zuranolone 50 mg: Summary of One-Year Results

This cohort of the ongoing Phase 3 SHORELINE Study is evaluating the safety and tolerability of zuranolone 50 mg in adults 18-75 who have MDD.

• 199 people with MDD (HAMD-17 ≥20 and Montgomery Asberg Depression Rating Scale (MADRS) ≥28) were treated with an initial dose of zuranolone 50 mg once nightly for 14 days and had the opportunity to be followed for up to one year.
• The mean baseline HAMD-17 score (± SD) at entry into the study was 25.1 ± 3.29 (n=199).
• At baseline, 81 (40.7%) patients were on pre-existing antidepressant therapy (ADT) that was continued, while 118 (59.3%) were not on ADT.

Safety and tolerability of zuranolone 50 mg:

• Zuranolone 50 mg was generally well-tolerated with no new safety finding or trend identified in the long-term safety data available to date on patients followed up to one year who received a single or repeat dosing courses. Safety was assessed during treatment and in between treatment courses and over multiple treatment courses to inform tolerability over time and long-term.
• Over the entire study, 137 of 199 (68.8%) patients who initiated treatment with zuranolone 50 mg reported at least one adverse event, similar to the previously reported 30 mg cohort (68.0%). The majority of patients reported treatment emergent adverse events (TEAEs) with maximum severity of mild to moderate.
• The most common TEAEs reported >5% (N, % with TEAE) were somnolence (32; 16.1%), dizziness (30; 15.1%), headache (25; 12.7%), sedation (20; 10.1%), insomnia (14; 7.0%), nausea (13; 6.5%), and tremor (11; 5.5%).
• The types of TEAEs reported by patients receiving zuranolone 50 mg were similar to those previously reported for zuranolone 30 mg. The frequency of adverse drug reactions known to be associated with zuranolone, such as somnolence, dizziness, sedation, and tremor, were higher in the 50 mg cohort; however, the severity and outcome of events remained consistent with the 30 mg cohort and the overall safety profile of zuranolone.
• The percent of patients reporting TEAEs leading to discontinuation of study drug and withdrawal from study, respectively, were 6.5% (13/199) and 8.0% (16/199).
• There was no signal for increased suicidal ideation or suicidal behavior compared to baseline in any study period or dose cohort, as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS).
• The overall adverse event profile from this zuranolone 50 mg cohort is generally consistent with the previously reported SHORELINE Study data, and the types of TEAEs reported are similar to what has been reported across the LANDSCAPE clinical program.

Efficacy of zuranolone 50 mg:

• At Day 15 following the initial 2-week treatment, the HAMD-17 mean change from baseline was -16.0 ± 6.04 (n=185).
  • 149 (74.9%) patients achieved response (at least 50% reduction from baseline) and 80 (40.2%) achieved remission (HAMD ≤7).
  • Of the 149 responders, 3 withdrew from the study prior to Day 28, leaving 146 beyond Day 28.
• 79.5% of the 146 patients who responded to the initial 2-week treatment received at most one additional zuranolone treatment course during their time in the study.
  • 54.8% (N=80) received 1 treatment course in total.
  • 24.7% (N=36) received 2 treatment courses in total.
  • 10.3% (N=15) received 3 treatment courses in total.
  • 6.8% (N=10) received 4 treatment courses in total.
  • 3.4% (N=5) received 5 treatment courses in total.
• The proportion of patients receiving zero or at most 1 additional treatment course was similar regardless of use of antidepressant therapy at baseline.

About the SHORELINE Study

The SHORELINE Study (217-MDD-303) is an ongoing Phase 3, open-label, 1-year longitudinal study evaluating the safety, tolerability, and need for repeat dosing with zuranolone in adults with MDD. The study is comprised of multiple cohorts, including a completed cohort with zuranolone 30 mg as a starting dose and an ongoing cohort with zuranolone 50 mg as a starting dose; both cohorts are administered zuranolone once nightly for 14 days. Enrollment of an additional 300 patients in the 50 mg cohort is ongoing. Patients who achieve a response after the first treatment course are eligible to remain on study with the opportunity to receive additional treatment courses as needed. The need for repeated dosing is assessed every 14 days based on the results of a patient-reported PHQ-9 (≥10) and HAMD-17 (≥20) assessment. There is a minimum of 56 days between zuranolone 14-day courses, to allow for a maximum of five courses over the 12-month study period. The complete 12-month data from the zuranolone 30 mg cohort and initial interim data from the zuranolone 50 mg cohort read out in early 2021.

About Major Depressive Disorder (MDD)

Major depressive disorder (MDD) is a common but serious mood disorder in which people experience depressive symptoms that impair their social, occupational, educational, or other important functioning, such as a depressed mood or loss of interest or pleasure in daily activities, consistently for at least a two-week period. It is estimated that approximately 19 million people in the U.S. and more than 250 million people worldwide suffer from MDD each year. While antidepressants are widely used to treat MDD, large-scale studies have demonstrated the need for additional therapies with a differentiated profile.

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 Breakthrough Therapy Designation by the U.S. Food & Drug Administration.

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

About Sage Therapeutics

Sage Therapeutics is a biopharmaceutical company committed to developing novel therapies with the potential to transform the lives of people with debilitating disorders of the brain. We are pursuing new pathways with the goal of improving brain health, and our depression, neurology and neuropsychiatry franchise programs aim to change how brain disorders are thought about and treated. Our mission is to make medicines that matter so people can get better, sooner. For more information, please visit www.sagerx.com.

About Biogen

At Biogen, our mission is clear: we are pioneers in neuroscience. Biogen discovers, develops and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative 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, Kenneth Murray and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today Biogen has the leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics and is focused on advancing research programs in multiple sclerosis and neuroimmunology, Alzheimer’s disease and dementia, neuromuscular disorders, movement disorders, ophthalmology, neuropsychiatry, immunology, acute neurology and neuropathic pain.

We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media - Twitter, LinkedIn, Facebook, YouTube.

Source: Sage Therapeutics, Inc.

Posted: December 2021