The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of esketamine nasal spray (Spravato, Janssen-Cilag) in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) for adults with treatment-resistant major depressive disorder (TRD).
Patients are considered to have TRD if they have not responded to at least two different treatments with antidepressants in the current moderate to severe depressive episode.
Spravato will be available as a 28 mg nasal spray solution.
The safety and efficacy of esketamine for TRD was evaluated in five phase 3 studies: three short-term studies, one randomized withdrawal and maintenance of effect study, and one long-term safety study.
“Data from these studies, which included more than 1600 esketamine-treated patients, demonstrated that treatment with esketamine nasal spray plus a newly initiated oral antidepressant, compared to a newly initiated antidepressant plus placebo nasal spray as an active standard-of-care comparator, was associated with a reduction in depressive symptoms, as early as day 2,” Janssen said in a news release.
In a short-term (1 month) study, about 70% of all esketamine-treated patients responded to treatment with at least a 50% reduction in symptoms. About half of all treated patients achieved remission, with few, if any, symptoms of depression.
The antidepressant effect was maintained for most patients and in the maintenance study, ongoing treatment with esketamine plus an oral antidepressant cut the risk of relapse by 51% in patients who achieved stable remission, and by 70% in those who achieved stable response, compared with oral antidepressants alone.
Esketamine nasal spray had a favorable risk/benefit profile, with no new safety concerns observed over a period of up to 52 weeks, the company said.
The most commonly observed side effects in patients with TRD were dissociation, dizziness, nausea, sedation, headache, vertigo, dysgeusia (impaired sense of taste), hypoaesthesia (decreased sense of touch or sensation), blood pressure increase, anxiety and vomiting. “These side effects were generally mild-to-moderate, transient, and happened on the day of dosing,” the company said.
Esketamine is an antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor, thought to help restore synaptic connections between brain cells in people with TRD, allowing for more activity and communication between specific regions of the brain.
A final decision on esketamine nasal spray by the European Commission (EC) is expected by the end of the year.