23 January 2020 - - US-based healthcare company Johnson and Johnson's (NYSE: JNJ) The Janssen Pharmaceutical Companies business has submitted a Type II Variation Application to the European Medicines Agency for Spravato (esketamine) nasal spray, the company said.

The application seeks to expand the use of esketamine nasal spray, beyond its current indication, 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 who have current suicidal ideation with intent.

The submission is based on results from two double-blind, randomised, placebo-controlled multicentre Phase 3 clinical studies (ASPIRE I and II), which evaluated both the efficacy and safety of esketamine nasal spray versus a placebo nasal spray when used in addition to comprehensive standard of care.

In these studies, SOC included initial hospitalisation and newly initiated and/or optimised antidepressant therapy, enhanced with extensive twice-weekly visits during the double-blind phase.

In both ASPIRE I and II, esketamine nasal spray combined with comprehensive SOC was associated with a reduction in depressive symptoms, and 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 nasal spray plus comprehensive SOC on symptoms of MDD was apparent as early as 4 hours after the first dose.

The safety profile was consistent with that observed in the clinical trial programme of esketamine in patients with treatment-resistant depression, with no new safety signals.

In the clinical trials, the most common adverse events were dizziness, dissociation, nausea, somnolence and headache.

In ASPIRE I and II, both esketamine nasal spray plus comprehensive SOC and placebo nasal spray plus comprehensive SOC resulted in an improvement in severity of suicidality as measured by the revised Clinical Global Impression of Severity of Suicidality (CGI-SS-R) at 24 hours after the first dose.

The treatment difference between the two groups on this secondary endpoint was not statistically significant.

This may be due to the substantial beneficial effects of comprehensive SOC used in the clinical trial, including the impact of inpatient psychiatric hospitalisation in diffusing the acute suicidal crisis in subjects in both treatment groups.

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

As an antagonist of the N-methyl-D-aspartate glutamate receptor. Spravato (esketamine) nasal spray offers the first new mechanism of action in 30 years to treat major depressive disorder.

Esketamine nasal spray is self-administered through a single-use nasal spray device, offering a novel mode of drug administration for the treatment of MDD.

The decision to prescribe esketamine nasal spray should be determined by a psychiatrist.

Esketamine nasal spray was approved by the European Commission for use in combination with a selective serotonin reuptake inhibitor or serotonin and norepinephrine reuptake inhibitor, in adult patients with treatment-resistant major depressive disorder in December 2019, and was approved for use in TRD patients by the conjunction with an oral antidepressant, for adults living with treatment-resistant depression by the US Food and Drug Administration in March 2019.

The FDA granted Breakthrough Therapy designation to esketamine nasal spray for major depressive disorder with imminent risk for suicide in August 2016.

Major depressive disorder affects nearly 40 m people of all ages in Europe and is one of the leading causes of disability worldwide.

Individuals with depression, including MDD, 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.

At its worst, MDD can be fatal, with MDD patients demonstrating a 20-fold higher risk of suicide than the rest of the population.

Despite treatment advances, currently available antidepressant medications can take between four to six weeks to reach their full effect, and one-third of people who suffer from MDD do not respond to these treatments.