The Janssen Pharmaceutical Companies of Johnson & Johnson has submitted a New Drug Application (NDA) to the FDA for esketamine nasal spray. Janssen is seeking FDA approval of esketamine for treatment-resistant depression in adults.
Esketamine is an investigational, rapidly acting antidepressant that works differently than currently available therapies for major depressive disorder. Through glutamate receptor modulation, esketamine is thought to help restore connections between brain cells in people with treatment-resistant depression.
“Of the nearly 300 million people who suffer from major depressive disorder worldwide, about one-third do not respond to currently available treatments.3,4 This represents a major unmet public health need,” said Mathai Mammen, M.D., Ph.D., global head, Janssen Research & Development, LLC. “We are committed to working with the FDA to bring this new treatment option to U.S. patients with treatment-resistant depression and to the medical community.”
The NDA is based on five pivotal Phase 3 studies of esketamine nasal spray in patients with treatment-resistant depression: three short-term studies, one withdrawal maintenance of effect study, and one long-term safety study. Data from these studies demonstrate that treatment with esketamine nasal spray plus a newly initiated oral antidepressant compared to placebo nasal spray plus a newly initiated antidepressant was associated with rapid reduction of depressive symptoms and delayed time to relapse of symptoms of depression.5,6
The long-term safety study showed that the esketamine doses studied were generally tolerated, with no new safety signals with dosing up to 52 weeks, compared to data from the short-term esketamine studies.7 The short-term esketamine Phase 3 study in adults with treatment-resistant depression included a newly initiated oral antidepressant in both the control and placebo groups.5
“Esketamine has been shown to target critical aspects of glutamate-mediated synaptic plasticity, thereby bringing about rapid and sustained improvement in people with treatment-resistant depression,” said Husseini K. Manji, MD, Global Head, Neuroscience Therapeutic Area, Janssen Research & Development, LLC.
Synaptic plasticity refers to the strength of information that flows through synapses, the spaces where neurons, cells in the brain, are connected.
Esketamine nasal spray will be self-administered by patients under the supervision of health care professionals.
The U.S. FDA granted Breakthrough Therapy Designations for esketamine nasal spray for treatment-resistant depression and for a second indication, major depressive disorder with imminent risk for suicide.8 Janssen is currently conducting Phase 3 clinical studies for the second indication.
Janssen plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the esketamine treatment-resistant depression indication later in 2018.
1Duman RS. Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide. F1000Research. 2018;7:F1000 Faculty Rev-659. doi:10.12688/f1000research.14344.1.
2Dubovsky SL. What Is New about New Antidepressants? Psychotherapy and Psychosomatics. 2018;87(3):129-139. doi:10.1159/000488945.
3World Health Organization. Depression. Available at: http://www.who.int/mediacentre/factsheets/fs369/en/. Accessed June 2018.
4National Institute of Mental Health. Questions and Answers about the NIMH Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study — Background. Available at: https://www.nimh.nih.gov/funding/clinical-research/practical/stard/backgroundstudy.shtml. Accessed May 2018.
5V Popova, EJ Daly, M Trivedi, K Cooper, R Lane, P Lim, C Mazzucco, D Hough, ME Thase, RC Shelton, P Molero, E Vieta, M Bajbouj, H Manji, WC Drevets, JB Singh. Randomized, Double-Blind Study of Flexibly Dosed Intranasal Esketamine Plus Oral Antidepressant Versus Active Control in Treatment-Resistant Depression. Poster presented at: 2018 Annual Meeting of the American Psychiatric Association (APA); May 2018; New York, New York.
6EJ Daly, M Trivedi, A Janik, H Li, Y Zhang, X Li, R Lane, P Lim, AR Duca, D Hough, ME Thase, J Zajecka, A Winokur, I Divacka, A Fagiolini, WJ Cubala, I Bitter, P Blier, RC Shelton, P Molero, H Manji, WC Drevets, JB Singh. A Randomized Withdrawal, Double-blind, Multicenter Study of Esketamine Nasal Spray Plus an Oral Antidepressant for Relapse Prevention in Treatment-resistant Depression. Poster presented at: American Society of Clinical Psychopharmacology; May 2018; Miami, Florida.
7E Wajs, L Aluisio, R Morrison, EJ Daly, R Lane, P Lim, R Holder, G Sanacora, AH Young, S Kasper, AH Sulaiman, C Li, J Paik, H Manji, D Hough, WC Drevets, JB Singh. Long-Term Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Patients with Treatment-Resistant Depression: Phase 3, Open Label Safety and Efficacy Study (SUSTAIN-2). Poster presented at: The American Society of Clinical Psychopharmacology Meeting; May 2018; Miami, Florida.
8Janssen Press Release. Esketamine Receives Breakthrough Therapy Designation from U.S. Food and Drug Administration for Major Depressive Disorder with Imminent Risk for Suicide. Available at: https://www.jnj.com/media-center/press-releases/esketamine-recieves-breakthrough-therapy-designation-from-us-food-and-drug-administration-for-major-depressive-disorder-with-imminent-risk-of-suicide. Accessed May 2018.