Janssen Submits Supplemental New Drug Application to U.S. FDA for SPRAVATO® (esketamine) CIII Nasal Spray for the Rapid Reduction of Depressive Symptoms in Adults with Major Depressive Disorder Who Have Active Suicidal Ideation with Intent

If approved, SPRAVATO® would be the first treatment for this severely ill population(1) who historically have been excluded from antidepressant clinical trials

Submission is based on data from the ASPIRE I & II trials evaluating the efficacy and safety of SPRAVATO® in adults with major depressive disorder who have active suicidal ideation with intent

TITUSVILLE, NJ, USA I October 2, 2019 I The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (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 high-risk patient population when used in addition to comprehensive standard of care (SOC). In these studies, comprehensive SOC included initial hospitalization and newly initiated and/or optimized antidepressant therapy.2,3,4

"This submission is a significant step in helping a vulnerable patient population by providing a potential treatment option to rapidly reduce symptoms of depression in adults with active suicidal ideation with intent, which constitutes a psychiatric emergency that requires immediate intervention," said Husseini K. Manji, M.D., Global Head, Neuroscience Therapeutic Area, Janssen Research & Development, LLC. "It extends our focus on severe manifestations of major depressive disorder beyond the current indication for treatment-resistant depression."

The data from the ASPIRE I & II trials were recently 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 (p=0.006) compared to placebo plus SOC in rapidly reducing symptoms of major depressive disorder. In these studies, comprehensive SOC included initial hospitalization and newly initiated and/or optimized antidepressant therapy.2,3,4

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 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. This may be due to the substantial beneficial effects of comprehensive SOC utilized in the clinical trial, including the immediate impact of inpatient psychiatric hospitalization in diffusing the acute suicidal crisis in patients in both treatment groups.2,3,4

The FDA granted Breakthrough Therapy designation to esketamine nasal spray for major depressive disorder with imminent risk for suicide in August 20165 and approved SPRAVATO® (esketamine) CIII nasal spray, in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression in adults on March 5, 2019.6

About the ASPIRE I & II Trials
At 24 hours after the first dose of study medication in ASPIRE I & II, the mean difference observed in the reduction of depressive symptoms between the SPRAVATO® plus SOC group and the placebo plus SOC group was 3.8 points and 3.9 points, respectively, as measured by the MADRS total score.2,3,4 

The effect of SPRAVATO® plus SOC on symptoms of major depressive disorder was apparent at four hours after the first dose. Between four hours and 25 days, both the SPRAVATO® and placebo groups continued to improve, and the magnitude of difference between the groups generally remained throughout the 25-day double-blind period. In the ASPIRE I & II trials, 54 percent and 47 percent, respectively, of the SPRAVATO® plus SOC group achieved remission (MADRS score ≤ 12) by the end of the double-blind period. The clinical improvement during the double-blind period was maintained over the nine-week follow-up period in both treatment groups, during which time the ongoing oral antidepressant was continued.2,3,4

In the ASPIRE I & II trials, SPRAVATO® plus SOC was well-tolerated with no new safety signals.2,3,4 The safety profile observed was consistent across the two Phase 3 studies in patients with major depressive disorder who have active suicidal ideation with intent and with previous studies of SPRAVATO® in patients with treatment-resistant depression.6 In the clinical trials, the most common side effects of SPRAVATO® plus SOC were dizziness, dissociation, nausea, somnolence, blurred vision, vomiting, paresthesia, increased blood pressure and sedation.2,3,4

About SPRAVATO®
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.6,9,10,11,12,13

SPRAVATO® (esketamine) CIII nasal spray is approved in the United States for use in conjunction with an oral antidepressant in adults with treatment-resistant depression (TRD) and has been submitted for health authorities' review for TRD in other markets around the world, including Europe.6,14 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 2016.5

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.15 With approximately 17 million adults diagnosed in the U.S., people with MDD experience suffering from a serious, biologically-based disease that has a significant negative impact on all aspects of life, including quality of life and function.16,17

About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension. 

Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal. Janssen Research & Development, LLC is part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

What is SPRAVATO®?
SPRAVATO® is a prescription medicine, used along with an antidepressant taken by mouth, for treatment-resistant depression (TRD) in adults.

SPRAVATO® is not for use as a medicine to prevent or relieve pain (anesthetic). It is not known if SPRAVATO® is safe or effective as an anesthetic medicine.

It is not known if SPRAVATO® is safe and effective in children.

  1. Melander H, Salmonson T, Abadie E, et al: A regulatory Apologia--A review of placebo-controlled studies in regulatory submissions of new-generation antidepressants. Eur Neuropsychopharmacol 2008;18(9):623-627.
  2. Carla Canuso, et al. Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients at imminent risk for suicide: new data from a global registration program. Presented at European College of Neuropsychopharmacology (ECNP) congress; September 2019; Copenhagen, Denmark.
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  4. Dawn Ionescu, Carla Canuso, Dong-Jing Fu, Xin Qiu, Rosanne Lane, Pilar Lim, David Hough, Wayne Drevets, Husseini Manji. Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients at imminent risk for suicide: ASPIRE-2 study. Presented at European College of Neuropsychopharmacology (ECNP) congress; September 2019; Copenhagen, Denmark.
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  12. M Fedgchin, M Trivedi, EJ Daly, R Melkote, R Lane, P Lim, D Vitagliano, P Blier, M Fava, M Liebowitz, A Ravindran, R Gaillard, H Ameele, H Manji, D Hough, WC Drevets, JB Singh. Randomized, Double-Blind Study of Fixed-Dosed Intranasal Esketamine Plus Oral Antidepressant vs. Active Control in Treatment-Resistant Depression. Poster presented at: 9th Biennial Conference of the International Society for Affective Disorders (ISAD) and the Houston Mood Disorders Conference; September 2018; Houston, TX.
  13. Rachel Ochs-Ross, M.D., Ella J. Daly, MD, Yun Zhang, Ph.D., Rosanne Lane, M.A.S., Pilar Lim, Ph.D., Karen Foster, B.S., David Hough, M.D., Husseini Manji, M.D., Wayne C. Drevets, M.D., Gerard Sanacora, M.D., Ph.D., Caleb Adler, M.D., Rupert McShane, M.D., Raphaël Gaillard, M.D., Ph.D., Jaskaran B. Singh, M.D. Efficacy and safety of intranasal esketamine plus an oral antidepressant in elderly patients with treatment-resistant depression. Poster presented at: American Psychiatric Association (APA) Annual Meeting; May 2018; New York, NY.
  14. Janssen Press Release. Janssen Announces U.S. FDA Approval of SPRAVATO® (esketamine) CIII Nasal Spray for Adults with Treatment-Resistant Depression (TRD) Who Have Cycled Through Multiple Treatments Without Relief. Available at: https://www.janssen.com/janssen-announces-us-fda-approval-SPRAVATO®-esketamine-ciii-nasal-spray-adults-treatment-resistant. Accessed March 2019.
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SOURCE: Janssen Pharmaceutical Companies of Johnson & Johnson

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