"Study in adults with treatmentresistant depression marks the first time an antidepressant has achieved superiority in a clinical trial for major depressive disorder that included a newly initiated oral antidepressant in both the control and placebo groups  Study in elderly patients is the first large clinical trial in treatmentresistant depression in this population  Results demonstrate the potential of esketamine nasal spray to address a significant unmet need for the more than  percent of people suffering from major depressive disorder who do not respond to two or more currently available antidepressants     News provided by Janssen Pharmaceutical Companies of Johnson  Johnson  https May    ET Share this article    javascriptvoid   javascriptvoid   javascriptvoid   javascriptvoid   javascriptvoid   javascriptvoid   TITUSVILLE N.J. May   PRNewswire  The Janssen Pharmaceutical Companies of Johnson  Johnson today announced the results from two Phase  clinical studies of the investigational compound esketamine nasal spray in patients with treatmentresistant depression. These studies will be presented at the American Psychiatric Association Annual Meeting taking place May  in New York NY.  Data from a study in adults with treatmentresistant 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. The study defined treatmentresistant as patients who had not responded to two or more currently available antidepressants of adequate dose and duration in the current episode of depression.  Data from a second study in elderly patients aged  and older with treatmentresistant depression which is the first study of its kind showed treatment with flexibly dosed esketamine plus a newly initiated oral antidepressant demonstrated clinically meaningful effects compared to placebo nasal spray plus a newly initiated oral antidepressant. However the study narrowly missed statistical significance for its primary efficacy endpoint.  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  years. With about  percent of patients with major depression failing to respond to currently available antidepressants treatmentresistant depression represents a major public health need said Husseini K. Manji MD Global Head Neuroscience Therapeutic Area Janssen Research  Development LLC. The positive Phase  results for esketamine nasal spray in adults with treatmentresistant 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. What makes this even more significant is that the response was rapid and this milestone was achieved in patients deemed to be treatmentresistant. 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. Theres 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. 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 httpsctt.ecPLxd Janssen announces new Phase  data re. treatmentresistant depression  httppo.stMUWqV  Results of the Study in Adults with TreatmentResistant Depression  In the Phase  study of adults with treatmentresistant depression patients were randomized to flexibly dosed esketamine nasal spray  mg or  mg added to a newly initiated oral antidepressant or placebo nasal spray added to a newly initiated oral antidepressant.  Primary Efficacy Endpoint The primary efficacy endpoint change from baseline in the Montgomerysberg 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  Least Squares Mean Difference Standard Error from placebo nasal spray plus a newly initiated oral antidepressant . .  Confidence Interval CI . . onesided p.. Secondary and Other Efficacy Endpoints The first key secondary endpoint onset of clinical response by  hours postdose that is maintained through day  numerically favored esketamine nasal spray plus an oral antidepressant vs. placebo nasal spray plus an oral antidepressant but did not meet statistical significance sided p.. The other two key secondary endpoints Sheehan Disability Scale SDS a subjectreported outcome measure widely used and accepted for assessment of functional impairment and associated disability and Patient Health Questionnaire PHQ a selfreport scale assessing depressive symptoms could not be formally evaluated since onset of clinical response was not statistically significant. Among other endpoints response rate was notable with . responding in the esketamine group vs.  in the placebo group at  days response   improvement in MADRS from baseline. Remission rate MADRS total score  at day  was . and . for the esketamine and placebo groups respectively.  The most common treatmentemergent adverse events  reported in the esketamine group were metallic taste nausea vertigo dizziness headache drowsiness dissociation blurred vision paraesthesia tingling sensation and anxiety. The most common treatmentemergent adverse events  reported in the placebo group were metallic taste and headache. Results of the Study in Elderly Patients with TreatmentResistant Depression  Janssen conducted a separate Phase  study in elderly patients with treatmentresistant depression. Elderly populations with major depressive disorder are historically hard to treat and often have comorbidities and longstanding depression. To improve tolerability patients were given a lower starting dose  mg of esketamine nasal spray flexibly dosed at  mg  mg or  mg plus a newly initiated oral antidepressant or placebo nasal spray plus a newly initiated oral antidepressant.  Primary Efficacy Endpoint 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 .  CI . . onesided p.. To put this into context an analysis of placebocontrolled data from three prior studies conducted by Duru and Fantino determined that a minimum change in MADRS of . was clinically meaningful. In addition the average difference is between  points for currently approved antidepressants vs. placebo.  Safety results were consistent with previous studies of esketamine in younger adult populations. The most common treatmentemergent adverse events  reported in the esketamine group were dizziness nausea headache fatigue increased blood pressure vertigo and dissociation. There were no treatmentemergent adverse events reported in  of patients in the placebo group. Esketamine nasal spray has an acceptable safety and tolerability profile based on the adverse event data from both Phase  studies. Adverse events and associated symptoms were seen predominately on the day of dosing and were generally transient and resolved on the day of dosing. These findings represent two of the five Phase  studies that comprise Janssens treatmentresistant depression program with esketamine nasal spray. The results from these studies will inform regulatory filings for esketamine nasal spray in treatmentresistant depression for which Janssen has received Breakthrough Therapy Designations from the U.S. FDA. Data from other Phase  studies will be presented later in . About the Studies  In both Phase  studies esketamine or placebo was provided in disposable nasal spray devices containing  l of solution i.e. two sprays and administered under the supervision of a health care professional. A bittering agent was added to placebo to simulate the taste of esketamine to help mask the treatment assignment. The study in adults with treatmentresistant depression was a Phase  doubleblind activecontrol flexibly dosed multicenter study using blinded raters conducted at  sites in Czech Republic Germany Poland Spain and the United States from August  to November . The study enrolled adults with moderatetosevere nonpsychotic recurrent or persistent depression and history of nonresponse to  antidepressants in the current episode of depression with one of them assessed prospectively. Nonresponders were randomized  to flexiblydosed esketamine nasal spray  or  mg twice weekly plus a newly initiated oral antidepressant N or placebo nasal spray plus a newly initiated oral antidepressant N. The primary efficacy endpoint  change from baseline to day  in MADRS total score  was assessed among patients who received  dose of nasal spray and oral study medication by mixedeffects model using repeated measures using a onesided significance level of .. .. For further information about this study visit the ClinicalTrials.gov httpsclinicaltrials.govctshowNCTtermNCTrank website. The study in elderly patients with treatmentresistant depression was a Phase  doubleblind multicenter activecontrolled study. Patients   years of age were randomized  to either esketamine nasal spray plus a new oral antidepressant N or placebo nasal spray plus a new oral antidepressant N. The primary endpoint was the change in the MADRS total score from day  baseline to day . Statistical analysis employed mixedeffects model repeated measures MMRM with a weighted combination test to account for an interim analysis for sample size reestimation using a onesided significance level of .. For further information about this study visit the ClinicalTrials.gov httpsclinicaltrials.govctshowNCTtermNCTrank website. About Esketamine  Esketamine nasal spray is an investigational compound being studied by Janssen Research  Development LLC as part of a global development program. Esketamine is a noncompetitive NmethylDaspartate NMDA receptor antagonist also known as a glutamate receptor modulator thought to help restore synaptic connections in brain cells in people with major depressive disorder. It has a novel mechanism of action meaning it works differently than currently available therapies for depression.  Esketamine received Breakthrough Therapy Designations from the U.S. FDA in November  for treatmentresistant depression and in August  for the indication of major depressive disorder with imminent risk for suicide.  About Major Depressive Disorder Major depressive disorder affects nearly  million people of all ages globally and is the leading cause of disability worldwide. 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. Although currently available antidepressants are effective for many patients about one third of patients do not respond to treatment and are thought to have treatmentresistant depression. About the Janssen Pharmaceutical Companies of Johnson  Johnson At the Janssen Pharmaceutical Companies of Johnson  Johnson we are working to create a world without disease. Transforming lives by finding new and better ways to prevent intercept treat and cure disease inspires us. We bring together the best minds and pursue the most promising science.  We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at  http Follow us at  http and  http  Cautions Concerning ForwardLooking Statements This press release contains forwardlooking statements as defined in the Private Securities Litigation Reform Act of  regarding product development and the potential benefits of esketamine. The reader is cautioned not to rely on these forwardlooking statements. These statements are based on current expectations of future events. 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 andor Johnson  Johnson. 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. A further list and description of these risks uncertainties and other factors can be found in Johnson  Johnsons Annual Report on Form K for the fiscal year ended January   including in Exhibit  thereto and the companys subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at  http  http or on request from Johnson  Johnson. None of the Janssen Pharmaceutical Companies or Johnson  Johnson undertakes to update any forwardlooking statement as a result of new information or future events or developments. . National Institute of Mental Health. Sequenced Treatment Alternatives to Relieve Depression STARD Study. Available at http_edn http Accessed May .  . The clinical relevance of changes in the MontgomeryAsberg Depression Rating Scale using the minimum clinically important difference approach. Available at https Accessed May .  . Khin NA https_uid et.al. 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. April . Available at https Accessed May .  . Johnson  Johnson 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 Accessed May .  . World Health Organization. Depression. Available at http Accessed May .  . Thase ME. Update on partial response in depression. J Clin Psychiatry. suppl ."