Long-Term Efficacy of Esketamine Nasal Spray Among Early and Delayed Responders: A Subgroup Analysis of the SUSTAIN-3 Study

Abstract: Objective: To describe the long-term efficacy of esketamine nasal spray (ESK) in adult patients (aged 18-64 years) with treatment-resistant depression (TRD) dosed according to US prescribing information, including an evaluation of early (day 8) and delayed (week 8) responders. Methods: SUSTAIN-3 (NCT02782104) was an open-label, long-term, phase 3 extension study composed of a 4-week induction phase (IND) and a variable-duration optimization/maintenance phase (OP/M). Clinician-reported disease severity was assessed per Montgomery-Åsberg Depression Rating Scale total score (MADRS). Safety was assessed on dosing days. Results: This analysis included 441 patients who entered during IND. Median duration of exposure to ESK was approximately 3.5 years (range, 1 day to >6 years). Mean baseline MADRS was 29.1. By IND end point, mean (SD) change from baseline in MADRS was −12.9 (9.67). Mean improvements were maintained over OP/M. By IND end point, 50.0% of patients achieved response (≥50% improvement in MADRS) and 36.3% achieved remission (MADRS ≤12). The proportion of patients in response and remission throughout OP/M appeared stable over time and was similar among early (n=65) and delayed (n=156) responders. At OP/M endpoint, 58.5% and 53.2% of early and delayed responders, respectively, continued to meet response criteria and 52.3% and 47.4%, respectively, met remission criteria. Treatment-emergent adverse events were consistent with the established safety and tolerability profile. No new safety signals were identified. Conclusion: This subgroup analysis demonstrated long-term efficacy (up to 6 years) of ESK in adults with TRD. Early and delayed responders showed similar rates of response and remission throughout OP/M.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 the long-term efficacy of ESK in adults (aged 18-64 years) with treatment-resistant depression dosed according to US prescribing information. Early and delayed responders showed similar rates of response and remission throughout the optimization/maintenance phase. Results were consistent with the established safety and tolerability profile. No new safety signals were identified.Name of Sponsoring Organization(s): Janssen Scientific Affairs, LLC, a Johnson & Johnson company