Efficacy TRD Long Term

In the 4-year analysis, SPRAVATO® (esketamine) was assessed for safety as well as secondary endpoints related to efficacy

Actor portrayal.

TRD=treatment-resistant depression in adults.

MDSI=depressive symptoms in adults with MDD with acute suicidal ideation or behavior.

The following data is drawn from an ongoing, Phase 3, open-label, long-term safety extension study in adults with treatment-resistant depression (TRD).

Limitations:

  • Results from an open-label, long-term safety study with no comparator group. Efficacy data not assessed for statistical significance
  • Generalizability of study findings may be limited by patients who chose to continue from the parent study and by exclusion of participants with significant comorbidities (psychiatric or medical, or substance dependence); decrease in sample size later in the trial may have implications for representativeness/generalizability of findings

TRD long-term safety extension study1

Study Design1

A subgroup analysis was conducted on a cohort of 1006 patients who met criteria consistent with the on-label population.

  • Patients eligible for this subgroup analysis were 18-64 years of age and received SPRAVATO® 56 mg or 84 mg twice weekly during induction (IND) phase and flexible dosing during optimization/maintenance (OP/M) phase; all patients should have taken a permitted oral AD for the duration of the study
TRD long-term safety extension study design: SPRAVATO® twice weekly during induction (IND) phase versus flexible dosing during optimization/maintenance (OP/M) phase

Primary endpoint: Number of participants with treatment-emergent adverse effects (TEAEs)

Outcome: No new safety signals observed, and during the combined IND and OP/M phases, 93.5% of patients experienced ≥1 TEAEs

  • Most TEAEs were mild or moderate in severity, and most events (96.7%) occurred and resolved on the same day as dosing

*Based on CGI-S and tolerability.
CGI-S=Clinical Global Impressions-Severity scale.

AD=antidepressant.

In an ongoing, long-term, open-label safety study, MADRS scores were consistent through interim analysis at 4 years1,2

Graph showing mean MADRS Total Scores (LOCF) during the induction (IND) phase and optimization/maintenance (OP/M) phase

4-year safety trial was composed of 2 phases: a 4-week IND phase and a variable OP/M phase.1,2

  • Of the 1006 patients studied in this cohort, 68.9% were treated with SPRAVATO® for at least 30 months

BL=baseline.

LOCF=last observation carried forward.

MADRS=Montgomery-Åsberg Depression Rating Scale.

Significantly delayed time to relapse in a long-term maintenance trial in adults with TRD with stable remission3,4*

Graph showing SPRAVATO® and oral antidepressant versus placebo and oral antidepressant data
  • Stable remission was defined as a MADRS total score of ≤12 in at least 3 of the last 4 weeks of the optimization phase

*Relapse was defined as a MADRS total score of ≥22 for 2 consecutive weeks and/or hospitalization for worsening depression, or any other clinically relevant event determined per clinical judgment to be suggestive of a relapse of depressive illness.

AD=antidepressant.

MADRS=Montgomery-Åsberg Depression Rating Scale.

TRD Study 2 (Long-term) Study Design3,4

Evaluated in a long-term (16 weeks), randomized, double-blind, parallel-group study in adults who were known remitters and responders to SPRAVATO®. Primary endpoint was time to relapse in patients in stable remission.3,4

Significantly delayed time to relapse in a long-term maintenance trial in adults with TRD with stable remission3,4

SPRAVATO® versus placebo TRD study design overview

Primary Endpoint

  • Time to relapse (cumulative distribution) during the maintenance phase among patients in stable remission
    • Relapse was defined as one of the following:
      • MADRS total score of ≥22 for 2 consecutive weeks
      • Hospitalization for worsening depression, or any other clinically relevant event determined per clinical judgment to be suggestive of a relapse of depressive illness

Secondary Endpoint

  • Time to relapse (cumulative distribution) during the maintenance phase among patients in stable response

Enrollment

  • 437 patients (aged 18-64 years) were directly enrolled
    • Patients who were directly enrolled received SPRAVATO® (56 mg or 84 mg twice/week) plus a new oral AD in a 4-week open-label induction phase before entering a 12-week optimization phase
  • 268 patients (aged 18-64 years) were transferred from short-term studies

Demographics and Baseline Characteristics

  • Median age 48 years (range 19-64 years); 66% female; 90% Caucasian, 4% Black
callout-background

Next: Safety and tolerability

Learn more

References:

1. Zaki N, Fu DJ, Daly E, et al. Long-term safety of esketamine nasal spray in adults with treatment-resistant depression: a subgroup analysis of the ongoing SUSTAIN-3 study. Poster presented at: Neuroscience Education Institute (NEI) Congress; November 4-7, 2021; Colorado Springs, CO.

2. Zaki N, Fu DJ, Daly E, et al. Long-term efficacy of esketamine nasal spray in adults with treatment-resistant depression: a subgroup analysis of the ongoing SUSTAIN-3 study. Poster presented at: Neuroscience Education Institute (NEI) Congress; November 4-7, 2021; Colorado Springs, CO.

3. SPRAVATO® [Prescribing Information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. July 2020.

4. Daly E, Trivedi M, Janik A, et al. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial [published online June 5, 2019]. JAMA Psychiatry. 2019;76(9):893-903. doi:10.1001/jamapsychiatry.2019.1189