Janssen announced the submission of a supplemental New Drug Application (sNDA) to the U.S. FDA seeking a new indication for Spravato (esketamine) CIII nasal spray for the rapid reduction of depressive symptoms in adult patients with major depressive disorder (MDD) who have active suicidal ideation with intent.
The submission is based on results from the Phase 3 ASPIRE I & II trials, which evaluated the efficacy and safety of Spravato versus placebo nasal spray in this population when used in addition to a comprehensive standard of care (SOC). In these studies, comprehensive SOC included initial hospitalization and newly initiated and/or optimized antidepressant therapy.
Data from ASPIRE 1 & II were presented at the 32nd European College of Neuropsychopharmacology (ECNP), which took place September 7-10 in Copenhagen, Denmark. The double-blind, randomized, placebo-controlled, multicenter studies both met their respective primary efficacy endpoint, which was a reduction in depressive symptoms at 24 hours after the first dose, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). In both studies, Spravato 84 mg plus SOC showed clinically meaningful and statistically significant superiority compared to placebo plus SOC in rapidly reducing symptoms of major depressive disorder.
The treatment difference between the two groups on the secondary endpoint of suicidality was not statistically significant. In the studies both Spravato plus comprehensive SOC and placebo plus comprehensive SOC resulted in improvement in the severity of suicidality (a composite endpoint including suicidal ideation and behavior) as measured by the revised Clinical Global Impression of Severity of Suicidality (CGI-SS-R) at 24 hours after the first dose. The most common adverse effects associated with the use of Spravato plus SOC were dizziness, dissociation, nausea, somnolence, blurred vision, vomiting, paresthesia, increased blood pressure and sedation
The FDA granted Breakthrough Therapy designation to esketamine nasal spray for treatment-resistant depression in November 2013 and for major depressive disorder with imminent risk for suicide in August 2016.
Spravato was approved by the FDA in March of 2019 for use in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression in adults.
About Major Depressive Disorder in Adult Patients Who Have Active Suicidal Ideation with Intent
Major depressive disorder (MDD) affects nearly 300 million people of all ages globally and is the leading cause of disability worldwide. Active suicidal ideation is not only thinking about suicide but having the intent to commit suicide, including planning how to do it. The lifetime prevalence of suicidal ideation for the general world population is about 9 percent. According to the 2017 National Survey on Drug Use and Health (NSDUH) by the Substance Abuse and Mental Health Services Administration (SAMHSA), 4.3 percent of U.S. adults ages 18 and older had thoughts about suicide, with the highest prevalence among adults ages 18 to 25. For those with mental health disorders, the rate is significantly higher. The exact numbers are unclear, but since suicidal ideation is a symptom of mental health disorders like major depression and bipolar disorder, the problem exists at a far greater percentage in this population.
Spravato is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor – an ionotropic glutamate receptor. It has a novel mechanism of action, meaning it works differently than currently available therapies for major depressive disorder.