Janssen Pharmaceutical announced results from a Phase 3 clinical study of the investigational product esketamine nasal spray in patients with treatment-resistant depression.
This clinical trial was a randomized, double-blind study of two fixed doses of esketamine, 56 mg and 84 mg. The study did not demonstrate statistical significance for the primary endpoint, change in a depression severity rating scale score from baseline to four weeks, for esketamine 84 mg plus oral antidepressant compared to oral antidepressant plus placebo. Therefore, based on the prespecified analysis plan, the esketamine 56 mg plus oral antidepressant group could not be formally evaluated in this study.
Importantly, results of analyses of the primary endpoint and key secondary endpoints numerically favored both esketamine plus oral antidepressant treatment groups over the oral antidepressant plus placebo group.
"Together with the recently announced results from four other Phase 3 studies, these data provide continued support for a positive benefit-risk assessment for esketamine nasal spray as a potentially novel treatment approach for patients living with treatment-resistant depression," said Husseini K. Manji, M.D, Global Head, Neuroscience Therapeutic Area, Janssen Research & Development. "One-third of patients with major depressive disorder do not respond to existing therapies, and they need new treatment options."
Janssen announced on September 4, 2018 that it submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for esketamine. Janssen is seeking FDA approval of esketamine for treatment-resistant depression in adults. The NDA is based on five pivotal Phase 3 studies of esketamine in patients with treatment-resistant depression: three short-term studies; one withdrawal maintenance of effect study; and one long-term safety study. Data from these studies demonstrate that treatment with esketamine plus a newly initiated oral antidepressant compared to placebo plus a newly initiated antidepressant was associated with rapid reduction of depressive symptoms and delayed time to relapse of symptoms of depression. The long-term safety study showed that the esketamine doses studied were generally tolerated, with no new safety signals with dosing up to 52 weeks.
This study defined treatment-resistant depression as patients who had not responded to two or more antidepressants of adequate dose and duration in the current episode of depression.
The results of this study showed that esketamine plus an oral antidepressant demonstrated safety and tolerability consistent with safety results reported in earlier esketamine Phase 2 and Phase 3 studies.
The study was an international, Phase 3, double-blind, active-controlled, multi-center study of 346 adults with treatment-resistant depression. Its purpose was to evaluate the efficacy and safety of fixed doses of esketamine plus an oral antidepressant. The primary objective was to evaluate the efficacy of switching adult patients with treatment-resistant depression from a prior antidepressant treatment (to which they had not responded) to a fixed dose of esketamine (56 mg or 84 mg) plus a newly initiated oral antidepressant compared with switching to a newly initiated oral antidepressant plus placebo, in improving depressive symptoms. Improvement in symptoms was assessed by the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from day one (pre-randomization) to the end of the four-week double-blind induction phase.
Results of the study were based on a mixed-effects model for repeated measures (MMRM) analysis of change in MADRS total score from baseline to day 28. The results numerically favored both esketamine plus an oral antidepressant groups over the oral antidepressant plus placebo group. The median unbiased estimate of the difference (95% confidence interval) between esketamine 84 mg plus oral antidepressant and the oral antidepressant plus placebo treatment groups was -3.2 (-6.88, 0.45), and that of esketamine 56 mg plus oral antidepressant and the...
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