Benzinga | Dec 1, 2021 06:31AM EST

Sage Therapeutics And Biogen Announce One-Year Zuranolone 50 mg Data In Ongoing Open-Label SHORELINE Study

In the zuranolone 50 mg cohort, the majority of patients who responded to an initial 14-day course received only one two-week course of treatment during the study and nearly 80% received only one or two treatment courses in total

Zuranolone 50 mg was generally well-tolerated with an overall adverse event profile consistent with data reported earlier and 6.5% of patients discontinuing study drug due to adverse events

Across the LANDSCAPE clinical program to date, zuranolone has consistently demonstrated rapid and sustained improvements in depressive symptoms and a well-tolerated safety profile

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.

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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.