Long-Term Safety and Efficacy of Esketamine Nasal Spray by Dosing Frequency in Adults With Treatment-Resistant Depression: Analysis of the SUSTAIN-3 Study

Abstract: Objective: To describe the long-term safety and efficacy of flexibly dosed esketamine nasal spray (ESK) in patients with treatment-resistant depression (TRD) from SUSTAIN-3 (NCT02782104). Methods: SUSTAIN-3, an open-label, phase 3, long-term extension study, assessed the safety and efficacy of ESK treatment plus an oral antidepressant in patients with TRD. The study consisted of a 4-week induction phase and a variable-duration optimization/maintenance phase (OP/M). During OP/M, ESK dosing frequency was adjusted based on depressive symptom severity. For this subgroup analysis, cohorts were assigned based on ESK mode dose frequency of weekly (QW), every other week (Q2W), or every 4 weeks (Q4W). Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Treatment-emergent adverse events (TEAEs) were monitored throughout the study. Results: A total of 1097 patients were included in the analysis; 591 (54%), 369 (34%), and 137 (12%) patients had an ESK mode dose frequency of QW, Q2W, and Q4W, respectively, during OP/M. At OP/M baseline, mean (SD) MADRS total scores were 16.2 (8.43), 10 (7.81), and 8.1 (7.29) for patients in the QW, Q2W, and Q4W dosing subgroups, respectively. Mean MADRS total scores generally remained stable over time for all subgroups. TEAEs were consistent with the established tolerability profile of ESK, with no new safety signals identified. Conclusion: This subgroup analysis showed consistent efficacy and safety of long-term ESK treatment in patients with a mode dose frequency of QW, Q2W, or Q4W. These results suggest that some patients with TRD may maintain clinical stability with less-frequent ESK dosing.Short Description: This subgroup analysis of SUSTAIN-3 (NCT02782104), an open-label, long-term, phase 3 extension study of esketamine nasal spray (ESK) in combination with an oral antidepressant, demonstrated consistent long-term safety and efficacy of ESK in patients with a cumulative mode dose frequency of weekly, every other week, or every 4 weeks. These findings support flexibility in the frequency of ESK dosing for some patients.Name of Sponsoring Organization(s): Janssen Scientific Affairs, LLC, a Johnson & Johnson company