Assessing the Need for Repeat Treatment Courses with Zuranolone in Adult Patients With Major Depressive Disorder With Elevated Anxiety: An Analysis of the Open-Label, Phase 3 SHORELINE Study

Abstract: Introduction Zuranolone is an investigational neuroactive steroid and positive allosteric modulator of synaptic and extrasynaptic GABAA receptors in clinical development as an oral, once-daily, 14-day treatment course for adults with major depressive disorder (MDD). Data for patients with MDD with/without elevated anxiety from the 30-mg Cohort of the ongoing, open-label, Phase 3 SHORELINE Study (NCT03864614), evaluating zuranolone safety/efficacy after initial/repeat treatment courses, are reported. Methods The SHORELINE Study includes adults (18-75 years) with MDD and 17-item Hamilton Rating Scale for Depression (HAMD-17) total score ≥20. Day (D)15 HAMD-17 responders (≥50% reduction from baseline) may continue year-long follow-up and receive episodic repeat treatments. Elevated anxiety was defined as HAMD-17 anxiety subscale score ≥39. Primary endpoint is safety/tolerability. Secondary endpoints include HAMD-17 change from baseline (CFB) and need for repeat treatment. Results Zuranolone 30-mg Cohort patients with MDD both with/without elevated anxiety (Nf569/156) were predominantly female (70.7%/55.8%) and White (79.1%/77.6%). Patients both with/without elevated anxiety reporting treatment-emergent adverse events (n=379[66.6%]/114[73.1%]) had mostly mild-to-moderate events (90.0%/93.9%). Mean±SD HAMD-17 at baseline, D15, and D70 (among D15 responders), respectively, was 26.3±3.8, 10.5±6.9 (CFB −15.9±7.2), and 13.5±8.7 (−12.9±9.1) with elevated anxiety and 21.6±2.6, 8.7±5.7 (−12.9±6.1), and 13.3±8.6 (−9.0±8.6) without elevated anxiety. Most patients both with/without elevated anxiety received 1-2 total treatment courses (68.2%/69.5%). Conclusions Patients with MDD both with/without elevated anxiety experienced improvements in depressive symptoms; most (≈70%) received 1-2 total treatment courses through 1 year. These results support further development of zuranolone as an episodic oral treatment for patients with MDD both with/without elevated anxiety.Short Description: In this post-hoc analysis of the ongoing, open-label, Phase 3 SHORELINE Study (NCT03864614)—designed to evaluate safety/efficacy of zuranolone in a naturalistic manner—patients with MDD with/without elevated anxiety from the 30-mg Cohort showed improvements in depressive symptoms following 14-day treatment(s), with approximately 70% of patients receiving ≤2 total treatments through 1 year of follow-up. These results support that episodic treatment with zuranolone may be effective in treating patients with MDD, regardless of baseline anxiety.Name of Sponsoring Organization(s): Sage Therapeutics, Inc. and Biogen, Inc.