Study supports positive benefit-risk assessment for esketamine nasal spray
ORLANDO, Fla. — Results from a randomized, double-blind study showed that esketamine nasal spray 84 mg plus oral antidepressant was not statistically superior to oral antidepressant plus placebo in adults with treatment-resistant depression.
However, the results of the primary endpoint and key secondary endpoints numerically favored both esketamine plus oral antidepressant treatment groups over the oral antidepressant plus placebo group, according to the poster data presented at Psych Congress.
“Individuals with depression, including major depressive disorder, experience continuous suffering from a serious, biologically based disease which has a significant negative impact on all aspects of life, including quality of life and function,” Maggie Fedgchin, PharmD, from Janssen Research and Development, told Healio Psychiatry. “One-third of patients with major depressive disorder do not respond to existing therapies, and they need new treatment options.”
This randomized, double-blind study compared efficacy and safety of fixed doses of esketamine nasal spray plus oral antidepressant to oral antidepressant plus placebo nasal spray in adults with treatment-resistant depression. Participants were randomly allocated 1:1:1 to receive esketamine (56 mg or 84 mg) or placebo nasal spray plus an antidepressant. Researchers assessed change from baseline to day 28 via the Montgomery-Asberg Depression Rating Scale.
Overall, 315 of 346 patients completed the treatment phase. Although the primary endpoint results numerically favored both esketamine plus antidepressant groups over antidepressant plus placebo, treatment with esketamine 84 mg plus antidepressant did not show statistical superiority over antidepressant plus placebo (-3.2; 95% CI, -6.88 to 0.45]). Because of this, the researchers could not formally evaluate esketamine 56 mg plus antidepressant, according to the poster.
The most common adverse events occurring in esketamine-treated patients included nausea, dissociation, dizziness, vertigo and headache. Most adverse events experienced on nasal spray dosing days were mild or moderate and resolved the same day.
“Safety and tolerability were consistent with safety results reported in earlier esketamine phase 2 and phase 3 studies,” Fedgchin told Healio Psychiatry. “The results of this study provide continued support for a positive benefit-risk assessment for esketamine nasal spray as a novel treatment approach for patients living with treatment-resistant depression.”
In September, Janssen submitted an NDA to the FDA for esketamine, citing data from five phase 3 studies that demonstrated treatment with esketamine plus a newly initiated oral antidepressant was linked to rapid reduction of depressive symptoms and delayed time to relapse of symptoms of depression, compared with placebo plus a newly initiated antidepressant. The current findings are consistent with Janssen’s commitment to develop esketamine for treatment-resistant depression, Fedgchin added. – by Savannah Demko
Fedgchin M. Randomized, double-blind study of fixed-dose esketamine nasal spray plus oral antidepressant vs. active control in treatment-resistant depression. Presented at: Psych Congress; Oct. 25-28, 2018; Orlando, Fla.
Disclosure: Fedgchin is employed by Janssen Research and Development.