The New Drug Application is based on data from 5 phase 3 studies of the efficacy and safety of esketamine nasal spray for treatment-resistant depression.
The Janssen Pharmaceutical Companies of Johnson & Johnson have submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for esketamine nasal spray. The company seeks FDA approval of esketamine for treatment-resistant depression in adults.
"Of the nearly 300 million people who suffer from major depressive disorder worldwide, about one-third do not respond to currently available treatments. This represents a major unmet public health need," said Mathai Mammen, MD, PhD, Global Head, Janssen Research & Development, LLC, in a statement. "We are committed to working with the FDA to bring this new treatment option to US patients with treatment-resistant depression and to the medical community."
If approved, the treatment will be self-administered by patients, under the supervision of health care professionals.
The NDA for esketamine nasal spray is supported by data from 5 phase 3 studies in patients with treatment-resistant depression. Patients with treatment-resistant depression are those whose depression has not responded to 2 or more treatments.
In a short-term study, patients were randomized to flexibly dosed esketamine nasal spray (56 mg or 84 mg twice weekly) plus a newly initiated oral antidepressant or placebo nasal spray plus a newly initiated oral antidepressant. Patients in the esketamine nasal spray arm experienced a significant clinical improvement in depressive symptoms, as measured by the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score (Least Squares Mean Difference Standard Error from placebo nasal spray plus a newly initiated oral antidepressant: -4.0 [1.69], 95% Confidence Interval [CI]: -7.31, -0.64; one-sided P = .010).
The most commonly-reported treatment-related adverse effects (>10%) in the esketamine treatment group were metallic taste, nausea, vertigo, dizziness, headache, drowsiness, dissociation, blurred vision, paranesthesia and anxiety, while in the placebo group metallic taste and headache were reported.
A longer-term study of 705 patients with treatment-resistant depression also randomized participants to 56 or 84 mg esketamine nasal spray plus oral antidepressant or a placebo plus antidepressant. The regimen consisted of intermittent dosing over 16 weeks. Among stable patients in remission, 24 (26.7%) of patients in the esketamine treatment arm relapsed, compared to 39 (45.3%) of patients in the placebo arm.
If esketamine nasal spray is approved, it would be the first new mechanism of action for treating depression in 30 years. The spray is a glutamate receptor modulator, which is thought to restore synaptic connections in the brains of patients with depression.
"Esketamine has been shown to target critical aspects of glutamate-mediated synaptic plasticity, thereby bringing about rapid and sustained improvement in people with treatment-resistant depression," said Husseini K. Manji, MD, Global Head, Neuroscience Therapeutic Area, Janssen Research & Development, LLC.
The FDA previously granted esketamine nasal spray a Breakthrough Therapy Designation for use in treatment-resistant depression as well as for a second indication, major depressive disorder with imminent risk for suicide. The company is currently testing esketamine nasal spray for the second indication in phase 3 clinical studies.