The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that data from a Phase 2 proof of concept clinical study of esketamine nasal spray, published in the American Journal of Psychiatry, showed that treatment with esketamine resulted in a statistically significant, clinically meaningful improvement in depressive symptoms at four hours, including a measure of suicidal ideation, in patients with major depressive disorder who were at imminent risk for suicide, compared to placebo. Unlike previous clinical trials of antidepressants which typically excluded suicidal patients, this study included people who were severely depressed and actively suicidal. All participants in the study received comprehensive clinical care, including hospitalization and the initiation or optimization of standard antidepressant medication through the duration of the study.
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) total scores, measured in the study, demonstrated the improvement in patients' depressive symptoms. Decreases in MADRS total score showed significant clinical improvement as early as four hours after the initial dose. Suicidal ideation, as measured by the MADRS suicidal thoughts item, was also significantly reduced at this four-hour time point. The study also utilized the Suicide Ideation and Behavior Assessment Tool (SIBAT) to assess suicide risk. The SIBAT is a novel instrument developed by Janssen and external collaborators that includes both patient-reported and clinician-rated sections. The tool is designed to measure rapid changes in suicidality and to address the limitations of existing suicide scales, including their limited sensitivity to discriminate among the treatment differences associated with rapid change.
"Major depressive disorder is among the most prevalent mental health conditions, and the incidence of attempted suicide in people with this condition is approximately 20-fold higher than that of the general population," 1,2 said Carla Canuso, MD, Senior Director, Clinical Development, Janssen Research & Development, LLC. "This study begins to explore if esketamine can rapidly reduce depressive symptoms in acutely suicidal patients and bridge the gap of several weeks between when a patient begins a standard antidepressant and when that treatment begins to work. The results of this study reinforce the potential of esketamine as an acute treatment for patients in crisis. We look forward to the completion of our ongoing Phase 3 trials and to bringing this important, potential new therapy to patients in desperate need."
Esketamine nasal spray belongs to a new class of investigational medicines in psychiatry known as glutamate receptor modulators that are thought to help restore synaptic connections in brain cells in people with major depressive disorder. If approved by the U.S. Food and Drug Administration (FDA) for this indication, esketamine would be the first treatment for patients with major depressive disorder assessed to be at imminent risk for suicide.4,5
Primary Efficacy Endpoint
The primary efficacy endpoint - change from baseline to four hours post-dose on day 1 in the MADRS total score - was achieved, with the mean change from baseline at four hours post-dose showing a rapid, clinically meaningful and statistically significant improvement in depressive symptoms of -13.4 (9.03) for esketamine nasal spray 84 mg plus standard of care, compared to -9.1 (8.38) for placebo nasal spray plus standard of care (p=0.015; effect size=0.61).
Secondary Efficacy Endpoints
A statistically significant difference in the MADRS total score favoring esketamine was also seen at 24 hours (p=0.015; effect size=0.65), but not at the double-blind endpoint, at which time the placebo plus standard of care group had received 4 weeks of standard antidepressant therapy. Additionally, esketamine nasal spray showed a rapid and statistically significant effect on suicidal ideation, as measured by the MADRS suicidal thoughts (MADRS-SI) item at four hours post-dose (p=0.002, effect size=0.67), but not at the 24-hour or double-blind endpoints. Analysis of the measure of suicide risk from the SIBAT scores showed numerically greater, but not statistically significant, decreases in clinician's judgment of suicide risk with esketamine nasal spray plus standard of care, compared to placebo nasal spray plus stan...
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