Benzinga | Mar 17, 2021 06:40AM EDT

Sage Therapeutics Reports 12-Month Data From 30 mg And 50 mg Cohort Of Zuranolone SHORELINE Study; Says 'more than 70% of patients who received 30 mg and 80% of patients who received 50 mg achieved positive response at Day 15'



In the now completed 30 mg zuranolone cohort, approximately 70% of participants with positive response to an initial 2-week treatment required at most one additional zuranolone treatment during the 12-month study

After the initial 2-week zuranolone treatment, more than 70% of patients who received 30 mg and 80% of patients who received 50 mg achieved positive response at Day 15

In both 30 mg and 50 mg cohorts, zuranolone was generally well-tolerated with an adverse event profile consistent with data reported earlier

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Sage Therapeutics, Inc. (NASDAQ:SAGE) today reported complete 12-month data from the 30 mg cohort and interim data from the 50 mg cohort of the ongoing Phase 3 open-label SHORELINE Study. This clinical study was designed to naturalistically follow patients with major depressive disorder (MDD) and evaluate the safety and tolerability of zuranolone 30 mg and 50 mg in adults for up to one year. For the primary endpoint of safety and tolerability, the data analyzed to date show that zuranolone was generally well-tolerated in both the 30 mg and 50 mg dose cohorts. Adverse events reported in the trial during the period analyzed were generally consistent with results seen in previous zuranolone clinical trials.

Secondary endpoints included response and remission as evaluated by the 17-item Hamilton Rating Scale for Depression (HAMD-17) and the number of times a patient received retreatment. Patients with a clinical response (decrease in HAMD-17 baseline score of ?50%) to the initial 14-day course of zuranolone 30 mg required a mean of 2.2 treatments in the 12-month study. As the first naturalistic, longitudinal, clinical development trial conducted in MDD, the SHORELINE Study provides real-world insight into the potential use of zuranolone, if successfully developed and approved, as an as-needed treatment for MDD, and builds on the data assembled in the LANDSCAPE clinical program to date. The Company plans to report additional data from patients in the 50 mg dose cohort in late 2021. Additionally, the Company plans to present additional data from the SHORELINE Study at medical and scientific conferences and in peer-reviewed journal articles.

"Sage embarked on the LANDSCAPE clinical program to evaluate the safety and efficacy of zuranolone with the ambition of reimagining the treatment for depression with the goal of a rapid-acting, durable, treat-as-needed option in a disease where innovation is lacking and the incidence rate has unfortunately increased exponentially in the last 20 years," said Barry Greene, Chief Executive Officer at Sage Therapeutics. "Today we are announcing additional positive data from the SHORELINE Study that demonstrate continued strong results from the 30 mg dose and strengthens our confidence in the potential of the 50 mg dose. Designed as a naturalistic study, these data approximate real-world evidence of use of zuranolone at 30 mg and 50 mg doses. We look forward to the results of the WATERFALL and CORAL Phase 3 pivotal data readouts in MDD this year."

Zuranolone 30 mg: Summary of Complete 12-Month Results from SHORELINE Study

The Phase 3 SHORELINE Study is evaluating the safety and tolerability of zuranolone 30 mg and 50 mg in adults 18-75 who have MDD with a baseline HAMD-17 total score ?20.

* 725 people with MDD (HAM-D ?20 and Montgomery Asberg Depression Rating Scale (MADRS) ?28) were treated with a first dose of zuranolone 30 mg once nightly for 14 days.

* The mean baseline HAM-D score (? SD) at entry into the study was 25.3 ? 4.1 (n=725).

* 173 (23.9%) did not achieve response to the first course and exited the study. Subjects were required by protocol to achieve response to continue into the naturalistic follow-up period. At Day 15, the mean change from baseline was -15.2 ? 7.1 (n=687); 505 (73.5%) patients achieved response and 276 (40.2%) achieved remission (HAM-D ?7). 304 (42%) patients were on pre-existing antidepressant therapy (ADT) which was continued, while 421 (58%) were on no ADT; there were no meaningful differences in efficacy outcomes between the two groups.

Safety and tolerability of initial treatment:

* In the first course of treatment (n=725), the adverse events reported were similar in nature and frequency to those previously reported for completed zuranolone studies, with 368 (51%) patients reporting at least one adverse event.

* The most common treatment emergent adverse events (TEAEs) (reported ?5%) were somnolence (86; 11.9%), headache (103; 14.2%), and dizziness (54; 7.4%). Most adverse events were mild or moderate.

* Similar adverse events were reported regardless of the presence or absence of ADT.

* Causes of adverse event-related discontinuations during the 14-day course of treatment were varied. The overall rate of study drug discontinuation due to TEAEs was 2.6%.

* No events of loss of consciousness were reported at any time during the study.

Retreatment:

489 patients were responders to initial 30 mg treatment and continued in the study beyond the first treatment course.

* Of the 489 patients continuing in the study, 210 (42.9%) patients used only the single initial zuranolone course, while 125 (25.6%) used a total of two courses, 58 (11.9%) used a total of three courses, 53 (10.8%) used a total of four courses, and 43 (8.8%) used a total of five courses.

* The number of zuranolone retreatments used were similar regardless of the presence or absence of ADT.

* The overall incidence rates of TEAEs during the second, third, fourth, and fifth treatment courses were, 42% (120/286), 28.6% (45/157), 29% (28/96), and 27.9% (12/43), respectively. The incidence of TEAEs in the first treatment course was 51% (368/725). The TEAEs were observed to decrease in frequency through the first three courses and remained stable over the next two courses.

* Safety on treatment, off-treatment, and in between treatments has shown a consistent pattern to date, in AE presentation across treatment courses.

* No signal on suicidality was identified during or in between treatment courses.

* Outcomes on efficacy measures and safety events were similar to those observed in the initial treatment course; and the presence or absence of ADT did not change the results.

Zuranolone 50 mg Dosing Cohort Initial Treatment Course:

Since May 2020, all newly enrolled patients in the SHORELINE Study received zuranolone 50 mg.

* In the 199 patients who received zuranolone 50 mg only (n=199), the mean HAM-D baseline score was 25.1 ? 3.3.

* At Day 15 of the initial treatment course in this group, the mean HAM-D change from baseline was -16 ? 6.0; 149/185 (80.5%) achieved response and 80/185 (43.2%) achieved remission.

* In this cohort the adverse event profile was similar to that seen in patients who received 30 mg zuranolone, with 62.8% (125/199) subjects reporting at least one AE. Events >5% of somnolence, dizziness, and sedation were observed to be more frequent in the 50 mg cohort, but were similar in severity to the events seen with 30 mg. Most adverse events were mild or moderate.

* The 50 mg cohort completed course one and is due for completion of the full 12-month follow-up in late 2021.