Janssen Investigational Treatment for Schizophrenia Shows Positive Efficacy, Delays Relapse

 Janssen Investigational Treatment for Schizophrenia Shows Positive Efficacy,                                 Delays Relapse  Independent Data Monitoring Committee Recommends Halting Trial and Unblinding Data Based on Treatment Efficacy  PR Newswire  TITUSVILLE, N.J., March 20, 2014  TITUSVILLE, N.J., March 20, 2014 /PRNewswire/ --Janssen Research & Development, LLC announced today that following an Independent Data Monitoring Committee (IDMC) recommendation based on positive efficacy, it has halted early a Phase 3 clinical study of paliperidone palmitate 3-month formulation, an investigational treatment for symptoms of schizophrenia in adults.  "We are really excited about this news because a medication's ability to delay time to relapse in schizophrenia has significant clinical and societal implications," said Husseini K. Manji, MD, Global Head, Neuroscience, Janssen Research & Development. "Being able to delay relapse can prove to be beneficial clinically to patients, to their caregivers and to the community."  The international, randomized, multicenter, double-blind clinical trial evaluated the efficacy of paliperidone palmitate 3-month formulation compared with placebo in delaying time to first occurrence of relapse of symptoms of schizophrenia. Study patients who were randomized to treatment were first stabilized with INVEGA^® SUSTENNA^® (paliperidone palmitate one-month formulation), an approved treatment for schizophrenia, prior to receiving the investigational 3-month formulation.  The primary outcome measure of the study was the time to first relapse event in the double-blind phase of the study. Time to relapse is defined as the time between randomization to treatment in the double-blind phase and the first documentation of a relapse. The study began in April 2012 and 509 patients were enrolled.  The planned interim analysis was conducted after 60 percent (42 events) of projected relapses occurred. The primary analysis of this study will be based on the interim results of the efficacy endpoint of time to first relapse. Events experienced by study patients after the decision to stop the study will be included in an additional analysis of the primary efficacy endpoint.  The study results will be presented at a future medical congress and will also be submitted for publication in a peer-reviewed journal.  The recommendation to stop and unblind the clinical study at this interim analysis was made by an independent data monitoring committee based on pre-specified criteria, specifically, achieving a statistically significant difference from placebo in delaying time to relapse based upon the interim analysis after 42 relapse events have occurred.  Study investigators will have the opportunity to switch patients enrolled in the study to standard of care treatment for schizophrenia.  Following a final analysis of the study and discussions with the U.S. Food and Drug Administration (FDA), Janssen Research & Development, LLC plans to file a New Drug Application with the U.S. FDA for paliperidone palmitate 3 month formulation by the end of 2014.  INVEGA^® SUSTENNA^® and the paliperidone palmitate 3-month formulation utilize Alkermes' proprietary NanoCrystal^® technology, which enables solubility of poorly water-soluble compounds.  About Paliperidone Palmitate (INVEGA^® SUSTENNA^®)  INVEGA^®SUSTENNA^®(paliperidone palmitate) is indicated for the treatment of schizophrenia in an injection administered once monthly after starting doses. Efficacy was established in four short-term studies and one longer-term study in adults.  IMPORTANT SAFETY INFORMATION FOR INVEGA^®SUSTENNA^®(paliperidone palmitate)    WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS.    oElderly patients with dementia-related psychosis treated with     antipsychotic drugs are at an increased risk of death.   oINVEGA® SUSTENNA® is not approved for the treatment of patients with     dementia-related psychosis.   oSee full Prescribing Information for Warnings and Precautions (5.1).    oContraindications: Paliperidone is contraindicated in patients with a     known hypersensitivity to either paliperidone, risperidone, or to any     components of the formulation.   oCerebrovascular Adverse Reactions: Cerebrovascular Adverse Reactions     (e.g., stroke, transient ischemic attacks), including fatalities, were     reported in placebo-controlled trials in elderly patients with     dementia-related psychosis taking oral risperidone, aripiprazole, and     olanzapine. The incidence of Cerebrovascular Adverse Reactions was     significantly higher than with placebo. INVEGA^®SUSTENNA^®is not     approved for the treatment of patients with dementia-related psychosis.   oNeuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom     complex, has been reported with the use of antipsychotic medications,     including paliperidone. Clinical manifestations include muscle rigidity,     fever, altered mental status, and evidence of autonomic instability (see     full Prescribing Information). Management should include immediate     discontinuation of antipsychotic drugs and other drugs not essential to     concurrent therapy, intensive symptomatic treatment and close medical     monitoring, and treatment of any concomitant serious medical problems.   oQT Prolongation: Paliperidone causes a modest increase in the corrected QT     (QTc) interval. Avoid the use of drugs that also increase QTc interval and     in patients with risk factors for prolonged QTc interval. Paliperidone     should also be avoided in patients with congenital long QT syndrome and in     patients with a history of cardiac arrhythmias. Certain circumstances may     increase the risk of the occurrence of torsades de pointes and/or sudden     death in association with the use of drugs that prolong the QTc interval.   oTardive Dyskinesia (TD): TD is a syndrome of potentially irreversible,     involuntary, dyskinetic movements that may develop in patients treated     with antipsychotic medications. The risk of developing TD and the     likelihood that dyskinetic movements will become irreversible are believed     to increase with duration of treatment and total cumulative dose, but can     develop after relatively brief treatment at low doses. Elderly female     patients appeared to be at increased risk for TD, although it is     impossible to predict which patients will develop the syndrome.     Prescribing should be consistent with the need to minimize the risk of TD     (see full Prescribing Information). Discontinue drug if clinically     appropriate. The syndrome may remit, partially or completely, if     antipsychotic treatment is withdrawn.   oMetabolic Changes: Atypical antipsychotic drugs have been associated with     metabolic changes that may increase cardiovascular/cerebrovascular risk.     These metabolic changes include hyperglycemia, dyslipidemia, and body     weight gain. While all of the drugs in the class have been shown to     produce some metabolic changes, each drug has its own specific risk     profile.         oHyperglycemia and Diabetes Mellitus: Hyperglycemia and diabetes          mellitus, in some cases extreme and associated with ketoacidosis,          hyperosmolar coma or death have been reported in patients treated          with all atypical antipsychotics (APS). Patients starting treatment          with APS who have or are at risk for diabetes mellitus should undergo          fasting blood glucose testing at the beginning of and during          treatment. Patients who develop symptoms of hyperglycemia during          treatment should also undergo fasting blood glucose testing. All          patients treated with atypical antipsychotics should be monitored for          symptoms of hyperglycemia. Some patients require continuation of          antidiabetic treatment despite discontinuation of the suspect drug.        oDyslipidemia: Undesirable alterations have been observed in patients          treated with atypical antipsychotics.        oWeight Gain: Weight gain has been observed with atypical          antipsychotic use. Clinical monitoring of weight is recommended.    oOrthostatic Hypotension and Syncope: INVEGA^®SUSTENNA^®may induce     orthostatic hypotension in some patients due to its alpha-blocking     activity. INVEGA^®SUSTENNA^®should be used with caution in patients with     known cardiovascular disease, cerebrovascular disease or conditions that     would predispose patients to hypotension (e.g., dehydration, hypovolemia,     treatment with antihypertensive medications). Monitoring should be     considered in patients for whom this may be of concern.   oLeukopenia, Neutropenia and Agranulocytosis have been reported with     antipsychotics, including paliperidone. Patients with a history of     clinically significant low white blood cell count (WBC) or drug-induced     leukopenia/neutropenia should have frequent complete blood cell counts     during the first few months of therapy. At the first sign of a clinically     significant decline in WBC, and in the absence of other causative factors,     discontinuation of INVEGA^®SUSTENNA^®should be considered. Patients with     clinically significant neutropenia should be carefully monitored for fever     or other symptoms or signs of infection and treated promptly if such     symptoms or signs occur. Patients with severe neutropenia (absolute     neutrophil count <1000/mm^3) should discontinue INVEGA^®SUSTENNA^®and     have their WBC followed until recovery.   oHyperprolactinemia: As with other drugs that antagonize dopamine D[2]     receptors, INVEGA^®SUSTENNA^®elevates prolactin levels and the elevation     persists during chronic administration. Paliperidone has a     prolactin-elevating effect similar to risperidone, which is associated     with higher levels of prolactin elevation than other antipsychotic agents.   oPotential for Cognitive and Motor Impairment: Somnolence, sedation, and     dizziness were reported as adverse reactions in subjects treated with     INVEGA^®SUSTENNA^®. INVEGA^®SUSTENNA^®has the potential to impair     judgment, thinking, or motor skills. Patients should be cautioned about     performing activities that require mental alertness such as operating     hazardous machinery, including motor vehicles, until they are reasonably     certain that INVEGA^®SUSTENNA^®does not adversely affect them.   oSeizures: INVEGA^®SUSTENNA^®should be used cautiously in patients with a     history of seizures or with conditions that potentially lower seizure     threshold. Conditions that lower seizure threshold may be more prevalent     in patients 65 years or older.   oAdministration: For intramuscular injection only. Care should be taken to     avoid inadvertent injection into a blood vessel.   oDrug Interactions: Strong CYP3A4 inducers: It may be necessary to increase     the dose of INVEGA^®SUSTENNA^®when a CYP3A4 strong inducer     (e.g. carbamazepine, rifampin, St. John's wort) is added. It may be     necessary to decrease the dose when a CYP3A4 strong inducer is     discontinued.   oPregnancy/Nursing: Patients should be advised to notify their physician if     they become pregnant/intend to become pregnant or intend to nurse during     treatment with INVEGA^®SUSTENNA^®.   oCommonly Observed Adverse Reactions for INVEGA^®SUSTENNA^®: The most     common adverse reactions in clinical trials in patients with schizophrenia     (greater than or equal to 5% and twice placebo) were injection site     reactions, somnolence/sedation, dizziness, akathisia and extrapyramidal     disorder.  Please see full Prescribing Information including Boxed Warning for INVEGA® SUSTENNA® (paliperidone palmitate) available at http://www.invegasustenna.com/important-product-information  About Janssen Research & Development, LLC  Janssen Research & Development, LLC is headquartered in Raritan, N.J. and has affiliated facilities in Europe, the United States and Asia. Janssen Research & Development is leveraging a combination of internal and external innovation to discover and develop novel medicines and solutions in five distinct therapeutic areas: Neuroscience, Oncology, Immunology, Infectious Diseases and Vaccines, and Cardiovascular and Metabolism. For more information about Janssen Research & Development, LLC visit www.janssenrnd.com.  Janssen Research & Development is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Driven by our commitment to patients, we work together to bring innovative ideas, products, services and solutions to address serious unmet medical needs around the world.  (This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding products in development. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate 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. Risks and uncertainties include, but are not limited to: challenges inherent in new product development, including obtaining regulatory approvals; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior and spending patterns or financial distress of purchasers of health care products and services; changes to governmental laws and regulations and domestic and foreign health care reforms; and general industry conditions including trends toward health care cost containment. 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 December 29, 2013, including in Exhibit 99 thereto, and our subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies or Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.)  Media Contact: Greg Panico 1-609-730-3061  Investor Relations: Stan Panasewicz 1-732-524-2524 Louise Mehrotra 1-732-524-6491  SOURCE Janssen Research & Development, LLC  Website: http://www.janssenrnd.com  
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