Safety, Tolerability, and Efficacy of Zuranolone Repeat Treatment Courses in Adult Patients With Major Depressive Disorder–An Analysis of the Open-Label, Phase 3 SHORELINE Study

Abstract: Introduction Rapid response and episodic treatment potential are important in the treatment of major depressive disorder (MDD). Zuranolone is a neuroactive steroid and positive allosteric modulator of synaptic and extrasynaptic GABAA receptors in development as an oral, once-daily, 14-day treatment for adults with MDD. SHORELINE is an ongoing, open-label, longitudinal, Phase 3 study (NCT03864614) assessing safety and efficacy of episodic treatment with zuranolone in adults with MDD. Results from initial and repeat treatment courses in patients initiating on zuranolone 30 mg are reported. Methods Eligible patients were adults (18-75 years) with MDD and 17-item Hamilton Rating Scale for Depression total score (HAMD-17)≥20. HAMD-17 responders (≥50% reduction from baseline) at Day (D)15 of treatment period 1 were followed-up for ≤48 weeks. Patients with posttreatment HAMD-17≥20 were eligible for repeat treatment with zuranolone 30 or 50-mg beginning at D70 of each treatment period. Results Patients initiating on zuranolone 30 mg (n=725) were predominantly female (67.4%); baseline mean(SD) HAMD-17 was 25.3(4.1), and mean(SD) change from baseline (CFB) in HAMD-17 at D15 was −15.2(7.1;n=687). Baseline mean(SD) HAMD-17 for retreatment was 25.8(4.4). For treatment courses 2–5 in initial responders, CFB HAMD-17 at D15 (of given treatment period) was −13.2(6.8;n=266), −13.7(6.4;n=151), −14.1(7.5; n=93), and −14.9(8.2;n=39), respectively. Incidence and severity of TEAEs were highest in treatment courses 1/2; no new trends identified with repeat treatments; no evidence for increased suicidal ideation. Conclusions Zuranolone was generally well tolerated and consistently led to improved depressive symptoms across all treatment courses, supporting episodic treatment of MDD with zuranolone.Short Description: In this analysis of the ongoing, open-label, Phase 3, longitudinal SHORELINE Study (NCT03864614)—designed to naturalistically evaluate the safety and efficacy of episodic treatment with zuranolone over up to 1 year—adult patients with major depressive disorder initially treated with zuranolone 30 mg showed similar improvement from baseline in depressive symptoms after first and repeat (zuranolone 30 or 50 mg) 14-day treatment courses with zuranolone. All treatment courses were generally well tolerated.Name of Sponsoring Organization(s): This study was sponsored by Sage Therapeutics, Inc., and Biogen Inc.