Safety and Efficacy of Zuranolone in Young Adults With Major Depressive Disorder: A Subgroup Analysis of the Open-Label, Long-Term, Phase 3 SHORELINE Study

Abstract: Introduction There is a greater prevalence of major depressive disorder (MDD) in young adults compared with older adults. 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 MDD. SHORELINE is an ongoing, open-label, Phase 3 study (NCT03864614) assessing safety and efficacy of episodic treatment with zuranolone 30 and 50 mg in adults with MDD. The SHORELINE post hoc analysis of zuranolone safety and efficacy in young adults are reported here. Methods Safety and efficacy (change from baseline [CFB] in 17-item Hamilton Rating Scale for Depression total score [HAMD-17]) were analyzed in young adults aged 18-24 years with MDD and HAMD-17≥20 in this interim analysis. Patients with posttreatment HAMD-17≥20 were eligible for repeat treatment. Results In SHORELINE, 68/924 (7.4%) patients were young adults with mean(SD) age 21.4(1.8) years; mean(SD) baseline HAMD-17 was 24.9(3.6) young adults and 25.3(3.9) overall. Mean(SD) CFB in HAMD-17 at Day (D)8/D15/D28 after the first treatment course was −10.1(6.2)/−13.3(7.2)/−11.6(7.3) in young adults and −11.2(6.6)/–15.4(6.9)/–13.6(7.8) in the overall population. Forty young adults (58.8%) achieved HAMD-17 response (≥50% reduction from baseline) at D15 after the first treatment course; of these, 21 (52.5%) and 9 (22.5%) received 1 or 2 treatment courses total, respectively. Forty-two young adults (61.8%) reported treatment-emergent adverse events, mostly (93%) mild/moderate. Conclusions Episodic treatment with zuranolone is generally well tolerated, with rapid and sustained improvement in depressive symptoms in young adults with MDD, similar to the overall population in SHORELINE.Short Description: In this post hoc interim analysis of the ongoing, open-label, Phase 3, 1-year longitudinal SHORELINE observational study (NCT03864614), zuranolone was generally well tolerated in young adults (aged 18–24 years) with MDD and demonstrated improvement in depressive symptoms similar to the overall study population (aged 18–75 years). Although sample size was small, among young adult Day-15 responders during initial treatment, 75% (30/40) received a total of ≤2 treatment courses over the 1-year study.Name of Sponsoring Organization(s): The study and this post hoc analysis were sponsored by Sage Therapeutics, Inc., and Biogen Inc.