The Janssen Pharmaceutical Companies of Johnson & Johnson announced the U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application (sNDA) for SPRAVATO? (esketamine) CIII nasal spray, taken with an oral antidepressant, to treat depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. SPRAVATO? is the first and only approved medicine that has been shown to reduce depressive symptoms within 24 hours, providing a new option for significant symptom relief until a longer-term, comprehensive treatment plan can take effect.

The effectiveness of SPRAVATO? in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated. Use of SPRAVATO? does not preclude the need for hospitalization if clinically warranted, even if patients experience improvement after an initial dose of SPRAVATO?. SPRAVATO? carries a Boxed Warning regarding a Risk Evaluation and Mitigation Strategy (REMS) and the risk of suicidal thoughts and behaviors.

Depression is the leading cause of disability worldwide and the condition most frequently associated with suicide. MDD is a serious disease that causes a significant, negative impact on the way people think, feel and act. Symptoms and severity vary by person and may include persistent feelings of sadness, hopelessness or tension; changes in sleep or appetite; difficulty concentrating or performing activities of daily living; lack of interest; and/or thoughts of harming themselves.

"Many people who live with depression know all too well the feeling of desperation. If that major depression progresses to active suicidal thoughts, it's crushing, and they need options to help change the trajectory of their acute depressive episode," said Theresa Nguyen, Chief Program Officer, Mental Health America. "Traditional oral antidepressants need weeks or more to take effect, so the availability of a medicine that can begin providing relief within a day is potentially life changing."

The sNDA approval is based on two identical Phase 3 clinical trials in which SPRAVATO? plus comprehensive standard of care demonstrated a significant, rapid reduction of depressive symptoms within 24 hours, with some patients starting to respond as early as four hours. SPRAVATO? plus comprehensive standard of care led to a 15.9 and 16.0 point decrease on the Montgomery-?sberg Depression Rating Scale (MADRS), a tool used to assess severity of depressive symptoms, in the two trials at 24 hours after the first dose of study medication. This compared to a reduction of 12.0 and 12.2 points in the placebo plus comprehensive standard of care group. The comprehensive standard of care included initial hospitalization, a newly initiated or optimized oral antidepressant and twice-weekly treatment visits for four weeks, during which patients received SPRAVATO? 84 mg or placebo nasal spray.

Both the SPRAVATO? and placebo groups continued to improve between four hours and 25 days, with 41 percent and 43 percent of the SPRAVATO? plus comprehensive standard of care group achieving clinical remission of depression (minimal or no symptoms) compared with 34 percent and 27 percent in the placebo groups, by the end of the double-blind period, in the two trials, respectively.

"It is astonishing to me that despite what we know about the risk of serious suicidal ideation in the context of major depression, patients with suicidal ideation have previously been excluded from nearly all studies examining antidepressant treatment efficacy. There is an immense need for high quality evidence showing effective and rapid antidepressant action in this population," said Gerard Sanacora,* Ph.D., M.D., Director, Yale Depression Research Program, Co-Director, Yale New Haven Hospital Interventional Psychiatry Service, and esketamine clinical trial investigator. "The clinical trials supporting this new indication provide compelling evidence that esketamine may offer clinicians a new way to provide support to patients quickly in the midst of an urgent depressive episode and help set them on the path to remission."

In the two Phase 3 trials, improvement in the severity of suicidality at 24 hours was measured using a standardized global scale. The treatment difference between the two groups was not statistically significant on this key secondary endpoint. Both SPRAVATO? and placebo in combination with comprehensive standard of care showed a similar reduction on this measure.

The safety profile observed in the trials was consistent with previous studies of SPRAVATO? in treatment-resistant depression (TRD), adding to the established body of safety and efficacy evidence. The most common side effects included dissociation (feeling disconnected from yourself, your thoughts, feelings, space and time), dizziness, sedation (sleepiness), increased blood pressure, hypoesthesia, vomiting, euphoric mood and vertigo.

SPRAVATO? (esketamine) CIII nasal spray 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 (MDD).

SPRAVATO? is approved in the United States, in conjunction with an oral antidepressant, to treat adults with treatment-resistant depression (TRD) and depressive symptoms in adults with MDD with acute suicidal ideation or behavior. SPRAVATO? has been submitted for health authorities' review for TRD and adults with MDD who have current suicidal ideation with intent in other markets around the world, including Europe. The FDA granted Breakthrough Therapy Designation to esketamine nasal spray for TRD in November 2013 and for MDD with imminent risk for suicide in August 2016.