2009;70[suppl 6]:4-9. All contents © Copyright Johnson & Johnson Services, Inc.1997-2020. SOC, standard of care. This news release focuses on two phase 3 clinical trials that evaluated the use of a drug called esketamine to treat depression. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; manufacturing difficulties and delays; changes in behavior and spending patterns or financial distress of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. Esketamine received Breakthrough Therapy Designations from the U.S. FDA in November 2013 for treatment-resistant depression and in August 2016 for the indication of major depressive disorder with imminent risk for suicide.4, Major depressive disorder affects nearly 300 million people of all ages globally and is the leading cause of disability worldwide.5 Individuals with depression, including major depressive disorder, 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.5 Although currently available antidepressants are effective for many patients, about one third of patients do not respond to treatment and are thought to have treatment-resistant depression.6, About the Janssen Pharmaceutical Companies of Johnson & Johnson. National Institute of Mental Health. 3. The primary endpoint was the change in the MADRS total score from day 1 (baseline) to day 28. To put this into context, an analysis of placebo-controlled data from three prior studies conducted by Duru and Fantino determined that a minimum change in MADRS of 1.9 was clinically meaningful.2 In addition, the average difference is between 2-3 points for currently approved antidepressants vs. placebo.3. ICER may revisit its analyses in a formal update to this report in the future. Esketamine, when used as an adjunct to an oral antidepressant, was shown to lower MADRS scores to a greater extent than antidepressant plus placebo use in short-term trials conducted to date. Fedgchin M, Trivedi M, Daly EJ, Melkote R, Lane R, Lim P, Vitagliano D, Blier P, Fava M, Liebowitz M, Ravindran A, Gaillard R, Ameele HVD, Preskorn S, Manji H, Hough D, Drevets WC, Singh JB. Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. 4. Among other endpoints, response rate was notable with 69.3% responding in the esketamine group vs. 52% in the placebo group at 28 days (response ≥ 50% improvement in MADRS from baseline). They were determined to continue the trials. Clipboard, Search History, and several other advanced features are temporarily unavailable. Bethesda, MD 20894, Copyright Among the patients without a history of hypertension, new antihypertensive medication was initiated by 2.1% (6/280) of patients in the esketamine/antidepressant group versus 1.2% (2/171) of … We bring together the best minds and pursue the most promising science. Am J Psychiatry. Background: Esketamine works in a similar fashion, but unlike other antidepressants it increases levels of glutamate, the most abundant chemical messenger in the brain. Of 230 patients who were randomized (115 per arm), 227 received study drug and were included in efficacy/safety analyses; 184 (80.0%) completed double-blind treatment. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC and/or Johnson & Johnson. Back in May, they made an announcement that even though they’d had both promising and disappointing results with esketamine nasal spray, they weren’t discouraged about its potential. Patients in both treatment groups experienced rapid reduction in Clinical Global Impression-Severity of Suicidality-revised score; the between-group difference was not statistically significant. Safety results were consistent with previous studies of esketamine in younger adult populations. Esketamine nasal spray is an investigational compound being studied by Janssen Research & Development, LLC as part of a global development program. Our results indicate that just 0.16 to 0.25 ml esketamine nebulized per minute, with lower nebulization efficacy when nebulizing higher concentrates of esketamine (this phenomenon is independent of the reduced bioavailability at higher ketamine concentrations). This study used data for those patients who had been undergoing treatment with esketamine nasal spray plus an oral antidepressant for 16 weeks and who, after meeting criteria for either stable remission (primary analysis) or stable response (secondary analysis), were randomized (separately) to continue treatment with esketamine nasal spray plus an oral antidepressant or to discontinue treatment with esketamine … These studies will be presented at the American Psychiatric Association Annual Meeting, taking place May 5-9 in New York, NY. Meaning Results of this first clinical trial of intranasal esketamine for treatment-resistant depression support study in larger trials. “The positive Phase 3 results for esketamine nasal spray in adults with treatment-resistant depression are exciting, particularly as they mark the first time an antidepressant has achieved superiority versus an active comparator in any clinical trial for major depressive disorder. In the Phase 3 study of adults with treatment-resistant depression, patients were randomized to flexibly dosed esketamine nasal spray (56 mg or 84 mg) added to a newly initiated oral antidepressant or placebo nasal spray added to a newly initiated oral antidepressant. Accessed May 2018. Patients ≥ 65 years of age were randomized 1:1 to either esketamine nasal spray plus a new oral antidepressant (N=72) or placebo nasal spray plus a new oral antidepressant (N=66). Am J Psychiatry 160 (11Suppl):1–60. Janssen conducted a separate Phase 3 study in elderly patients with treatment-resistant depression. In the clinical trials of esketamine that led to FDA approval for TRD, key exclusion criteria included active substance use disorder (or within 6 months), current or past psychosis, and bipolar disorder. World Health Organization. Bozymski KM, Crouse EL, Titus-Lay EN, Ott CA, Nofziger JL, Kirkwood CK. 2019 Jun 1;176(6):428-438. doi: 10.1176/appi.ajp.2019.19020172. Study design and disposition of patients. Accessibility J&J expects to read out more data from three other Phase 3 studies of the drug in treatment-resistant depression later this year. Published by Oxford University Press on behalf of CINP. Common antidepressants are slow-acting. This study confirmed rapid and robust reduction of depressive symptoms with esketamine nasal spray in severely ill patients with MDD who have active suicidal ideation with intent. You are now leaving jnj.com. Elderly populations with major depressive disorder are historically hard to treat and often have co-morbidities and long-standing depression. Results: doi: 10.4088/JCP.19m13191. Esketamine nasal spray has an acceptable safety and tolerability profile, based on the adverse event data from both Phase 3 studies. Statistical analysis employed mixed-effects model repeated measures (MMRM), with a weighted combination test to account for an interim analysis for sample size re-estimation, using a one-sided significance level of 0.025. Privacy, Help A Double-blind Study to Assess the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Participants Who Are Assessed to be at Imminent Risk for Suicide. However, the study narrowly missed statistical significance for its primary efficacy endpoint. TITUSVILLE, N.J., May 5, 2018 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the results from two Phase 3 clinical studies of the investigational compound esketamine nasal spray in patients with treatment-resistant depression. Johnson & Johnson Medical Devices Companies. “Janssen is fully committed to exploring the newest science in the area of mood disorders and bringing these discoveries to patients in need.”, Click to Tweet: Janssen announces new Phase 3 data re. Although statistical significance for the primary endpoint for the overall patient population studied was narrowly missed, results favored the esketamine nasal spray plus a newly initiated oral antidepressant group (median unbiased estimate of the difference from placebo nasal spray plus a newly initiated oral antidepressant: -3.6, 95% CI: -7.20, 0.07; one-sided p=0.029). Arlington, VA: American Psychiatric Publishing. J Clin Psychiatry. “With about 30 percent of patients with major depression failing to respond to currently available antidepressants1, treatment-resistant depression represents a major public health need,” said Husseini K. Manji, MD, Global Head, Neuroscience Therapeutic Area, Janssen Research & Development, LLC. potentially influence the results. Jan 8, 2020—Celon Pharma ($CLN.PL) today announced positive top-line results from a Phase II study of Falkieri (proprietary esketamine dry powder inhalation) in acute phase of treatment-resistant bipolar depression. Esketamine Receives Breakthrough Therapy Designation from U.S. Food and Drug Administration for Major Depressive Disorder with Imminent Risk for Suicide. These findings represent two of the five Phase 3 studies that comprise Janssen’s treatment-resistant depression program with esketamine nasal spray. Blair-West GW, Cantor CH, Mellsop GW, Eyeson-Annan ML (1999) Lifetime suicide risk in major depression: sex and age determinants. Conclusion: The corporation selling Esketamine did three trials. Change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale total score (primary efficacy endpoint) was analyzed using ANCOVA. “Exploratory analyses of efficacy data from major depressive disorder trials submitted to the US Food and Drug Administration in support of new drug applications,” Journal of Clinical Psychiatry. What makes this even more significant is that the response was rapid and this milestone was achieved in patients deemed to be treatment-resistant. Methods: Please see our Privacy Policy. Results from a second late-stage trial in older adults, however, fell short of demonstrating a statistically significant difference between the esketamine group and the control arm. Results: Of 230 patients who were randomized (115 per arm), 227 received study drug and were included in efficacy/safety analyses; 184 (80.0%) completed double-blind treatment. Depression. After a series of clinical trials, the pharmaceutical giant Johnson & Johnson is seeking government approval (in the U.S. and European Union) for its version of ketamine – esketamine … Accessed May 2018. For further information about this study, visit the ClinicalTrials.gov website. Safety results were consistent with previous studies of esketamine in younger adult populations. The study in question built on the results of a 2018 trial, qualifying as a phase 3 clinical trial, which is a study that assesses the effectiveness and the safety of the proposed treatment. After randomisation, participants were switched to another antidepressant plus esketamine or placebo. Data from a study in adults with treatment-resistant depression showed that flexibly dosed esketamine nasal spray plus a newly initiated oral antidepressant demonstrated a statistically significant, clinically meaningful rapid reduction of depressive symptoms as compared to placebo nasal spray plus a newly initiated oral antidepressant. Data from other Phase 3 studies will be presented later in 2018. Follow us at www.twitter.com/JanssenUS and www.twitter.com/JanssenGlobal. Results from a phase III clinical trial was published this week in the Americal Journal of Psychiatry, which was in place to test the efficacy and safety of Spravato, the FDA-approved esketamine nasal spray manufactured by Janssen Pharmaceuticals. Fu DJ, Ionescu DF, Li X, Lane R, Lim P, Sanacora G, Hough D, Manji H, Drevets WC, Canuso CM. -. -, Bremner JD, Krystal JH, Putnam FW, Southwick SM, Marmar C, Charney DS, Mazure CM (1998) Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS). Remission rate (MADRS total score ≤12) at day 28 was 52.5% and 31.0% for the esketamine and placebo groups, respectively. The most common treatment-emergent adverse events (>10%) reported in the esketamine group were metallic taste, nausea, vertigo, dizziness, headache, drowsiness, dissociation, blurred vision, paraesthesia (tingling sensation) and anxiety. 87 The overall results from different trials show that intranasal esketamine reduces suicidal risk and symptoms of depression, as measured through a reduced MADRS score. The primary efficacy endpoint, change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score, demonstrated the statistically significant clinical improvement in patients’ depressive symptoms for esketamine nasal spray plus an oral antidepressant at day 28 (Least Squares Mean Difference Standard Error from placebo nasal spray plus a newly initiated oral antidepressant: -4.0 [1.69], 95% Confidence Interval [CI]: -7.31, -0.64; one-sided p=0.010). This double-blind study (ASPIRE II) randomized adults (aged 18-64 years) with MDD having active suicidal ideation with intent to esketamine 84 mg or placebo nasal spray twice weekly for 4 weeks, given with comprehensive standard of care (hospitalization ≥5 days and newly initiated or optimized oral antidepressant[s]). Study design and disposition of patients. (5.69). The most pro-Esketamine biased studies couldn’t even find the drug was better than placebo(2). The most common adverse events among esketamine-treated patients were dizziness, dissociation, nausea, dysgeusia, somnolence, headache, and paresthesia. Keywords: Full results from TRANSFORM-2, a phase 3 trial that led to the FDA approval in March for esketamine (Spravato), appear Tuesday in the American Journal of Psychiatry. Available at: http://www.who.int/mediacentre/factsheets/fs369/en/. Epub 2019 Dec 4. The first key secondary endpoint (onset of clinical response by 24 hours post-dose that is maintained through day 28) numerically favored esketamine nasal spray plus an oral antidepressant vs. placebo nasal spray plus an oral antidepressant, but did not meet statistical significance (1-sided p=0.161). Greater improvement in Montgomery-Asberg Depression Rating Scale total score was observed with esketamine (mean [SD]: -15.7 [11.56]) vs placebo (-12.4 [10.43]), each with standard of care, at 24 hours (least-squares mean difference [SE]: -3.9 [1.39], 95% CI: -6.60, -1.11; 2-sided P = .006). J Trauma Stress 11:125–136. At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. If approved by the U.S. Food and Drug Administration (FDA), esketamine would be one of the first new approaches to treat refractory major depressive disorder available to patients in the last 50 years. 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. Pharmaceutical Companies of Johnson & Johnson, Advancing New Healthcare Solutions Through Collaboration, Reimagining the Way Healthcare Is Delivered, Learn About the Company's Rich Heritage at Our Digital Museum. Esketamine Nasal Spray Posts Positive Results in Two Phase 3 Trials May 06, 2018 NEW YORK CITY—Esketamine nasal spray reduced symptoms in patients with treatment-resistant depression in two Phase 3 clinical trials, Janssen Pharmaceutical Companies of Johnson & Johnson announced. The site you’re being redirected to is a branded pharmaceutical website. Non-responders were randomized (1:1) to flexibly-dosed esketamine nasal spray (56 or 84 mg twice weekly) plus a newly initiated oral antidepressant (N=114) or placebo nasal spray plus a newly initiated oral antidepressant (N=109). An open-label, long-term, multicentre trial of esketamine (SUSTAIN-2) ... with doses administered either weekly or fortnightly. The study in elderly patients with treatment-resistant depression was a Phase 3, double-blind, multicenter, active-controlled study. Adverse events and associated symptoms were seen predominately on the day of dosing and were generally transient and resolved on the day of dosing. The clinical relevance of changes in the Montgomery-Asberg Depression Rating Scale using the minimum clinically important difference approach. This was also noted at the earlier (4-hour) timepoint (least-squares mean difference -4.2, 95% CI: -6.38, -1.94). 2019 Oct 1;22(10):616-630. doi: 10.1093/ijnp/pyz039. Clinical Global Impression-Severity of Suicidality-revised (key secondary endpoint) was analyzed using ANCOVA on ranks of change. Contact Us with any questions or search this site for more information. Volume 29. The study was conducted from 2014-2015, and results were published in JAMA Psychiatry on December 27, 2017. Of course, investors want to see a return on their investment. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. © The Author(s) 2020. 8600 Rockville Pike 2020 Jun;54(6):567-576. doi: 10.1177/1060028019892644. Available at: http://www.nimh.nih.gov/about/director/2011/antidepressants-a-complicated-picture.shtml#_edn2. The most common treatment-emergent adverse events (>10%) reported in the esketamine group were dizziness, nausea, headache, fatigue, increased blood pressure, vertigo and dissociation. Thase ME. Unable to load your collection due to an error, Unable to load your delegates due to an error. Cautions Concerning Forward-Looking StatementsThis press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits of esketamine. 2020 May 12;81(3):19m13191. We collaborate with the world for the health of everyone in it. Frequency distribution of Clinical Global Impression-Severity of Suicidality-Revised (CGI-SS-r) score at baseline, 4 and 24 hours post-first dose, and day 25 (observed cases). The most common treatment-emergent adverse events (>10%) reported in the esketamine … The reader is cautioned not to rely on these forward-looking statements. A greater impact on more brain cells at one time. Int J Neuropsychopharmacol. Esketamine; depression; suicidal ideation; suicide risk. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Results of the Study in Elderly Patients with Treatment-Resistant Depression. Canuso CM, Singh JB, Fedgchin M, Alphs L, Lane R, Lim P, Pinter C, Hough D, Sanacora G, Manji H, Drevets WC. For further information about this study, visit the ClinicalTrials.gov website. Would you like email updates of new search results? New Phase 3 Data Show Esketamine Nasal Spray Demonstrated Rapid Improvements in Depressive Symptoms in Patients with Treatment-Resistant Depression, This site uses cookies as described in our. Responses to a subsequent question on which aspect of the post-dose symptoms was most concerning indicated that the idea of dissociative symptoms … J Clin Psychiatry. 5. Results: Adverse events related to increased BP were reported in 12.8% of all esketamine-treated patients (in double-blind trials: esketamine/antidepressant 11.6% vs. antidepressant/placebo 3.9%; OR 3.2 [1.9-5.8]). Participants entering from study ESKETINTRD3005 (NCT02422186) will self-administer esketamine nasal spray (28 mg in week 1; 28 or 56 mg in week 2; and 28, 56 or 84 mg in week 3 and 4) once weekly. A further list and description of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2017, including in Exhibit 99 thereto, and the company's subsequent filings with the Securities and Exchange Commission. Esketamine had worse results than placebo in two and slightly better results in one. Abstract Importance Approximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants. Patients with major depressive disorder (MDD) having active suicidal ideation with intent require immediate treatment. FOIA -, American Psychiatric Association (2003) Practice guideline for the assessment and treatment of patients with suicidal behaviors. Epub 2018 Apr 16. Your use of the information on this site is subject to the terms of our Legal Notice. To improve tolerability, patients were given a lower starting dose (28 mg) of esketamine nasal spray (flexibly dosed at 28 mg, 56 mg or 84 mg) plus a newly initiated oral antidepressant or placebo nasal spray plus a newly initiated oral antidepressant. The result? Learn more at www.janssen.com. treatment resistant #depression http://po.st/MUWq5V, Results of the Study in Adults with Treatment-Resistant Depression. The primary efficacy endpoint – change from baseline to day 28 in MADRS total score – was assessed among patients who received ≥1 dose of (nasal spray and oral) study medication by mixed-effects model using repeated measures using a one-sided significance level of 0.025. The study defined treatment-resistant as patients who had not responded to two or more currently available antidepressants of adequate dose and duration in the current episode of depression. All Rights Reserved. Accessed May 2018. People with Depression Get Rapid Relief. We are also pleased with the clinically meaningful outcomes for esketamine nasal spray in elderly patients, a population that often has greater disability and lower response rates.”, “There’s a critical need for new, rapidly acting and effective treatment options for people with major depressive disorder who do not respond to existing therapies,” said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC. April, 2011. Ann Pharmacother. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21527123. Use of this site constitutes your consent to application of such laws and regulations and to our Privacy Policy. Moreover, this trial results is thrilling as it is the first phase II study with esketamine in this indication focusing on the unmet needs brought by the medical professionals, regulatory, and, above all, the patients.” About the 03KET2018 study Psychiatry Research; (in press), 10.1016/j.psychres.2020.113495. You should view the News section and the most recent SEC Filings in the Investor section in order to receive the most current information made available by Johnson & Johnson Services, Inc. The other two key secondary endpoints (Sheehan Disability Scale [SDS], a subject-reported outcome measure widely used and accepted for assessment of functional impairment and associated disability, and Patient Health Questionnaire-9 [PHQ-9], a self-report scale assessing depressive symptoms) could not be formally evaluated since onset of clinical response was not statistically significant. J Affect Disord 55:171–178. Careers. EEO Is the Law | EEO Is the Law GINA Supplement | Do Not Sell My Personal Information. Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent: Double-Blind, Randomized Study (ASPIRE I). A bittering agent was added to placebo to simulate the taste of esketamine, to help mask the treatment assignment. The short-term trials compared four weeks’ intranasal esketamine (twice weekly) with placebo after a lead-in observational phase to confirm treatment resistance. For these people the recent development of treatments based on the drug ketamine have shown great promise.