Regulatory expansion submitted for SPRAVATO^® (esketamine) nasal spray

A submission of a Type II Variation Application to the European Medicines Agency (EMA) seeks to expand the use for SPRAVATO® (esketamine) nasal spray. The drug is intended as an acute short-term treatment, co-administered with oral antidepressant therapy, for the rapid reduction of depressive symptoms in adults with a moderate-to-severe depressive episode of major depressive disorder (MDD) who have current suicidal ideation with intent.

This submission, from Janssen, is based on results from two double-blind, randomised, placebo-controlled multicentre Phase III clinical studies, evaluating both the safety and efficacy of esketamine versus placebo when used in addition to comprehensive standard of care (SOC). SOC included hospitalisation and oral antidepressant therapy.

In the trials, esketamine nasal spray combined with SOC was associated with a reduction in depressive symptoms; it demonstrated clinically meaningful and statistically significant superiority over a placebo nasal spray plus comprehensive SOC in rapidly reducing symptoms of MDD at 24 hours after the first dose. The benefit of esketamine plus SOC on symptoms of MDD was apparent from four hours after the first dose.

“Patients with MDD who are assessed to be at imminent risk for suicide constitute a psychiatric emergency that require immediate intervention,” explains Professor Maurizio Pompili, Director, University Psychiatric Clinic, Sant’Andrea Hospital, Sapienza University of Rome, Italy. “While currently available antidepressants are effective in treating depressive symptomatology, they can often take weeks to achieve their full effects. This delay is potentially dangerous, especially since suicide risk is highest early in treatment.”

The safety profile was consistent to that seen in trials for its previous indication (esketamine in patients with treatment-resistant depression), with no new safety signals.

In October 2019, a supplemental New Drug Application was also submitted to the US Food and Drug Administration (FDA) for esketamine nasal spray for the rapid reduction of depressive symptoms in adult patients with MDD who have active suicidal ideation with intent.