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Janssen Investigational Treatment for Schizophrenia Shows Positive Efficacy, Delays Relapse

March 20, 2014

Independent Data Monitoring Committee Recommends Halting Trial and Unblinding Data Based on Treatment Efficacy

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.

    Elderly patients with
        dementia-related psychosis treated with
        antipsychotic drugs are at an increased risk of
        death.
    INVEGA(R) SUSTENNA(R) is not approved for
        the treatment of patients with dementia-related
        psychosis.
    See full Prescribing Information for
        Warnings and Precautions (5.1).
       -----------------------------------------------------
    --  Contraindications: Paliperidone is contraindicated in patients with a
        known hypersensitivity to either paliperidone, risperidone, or to any
        components of the formulation.
    --  Cerebrovascular 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.
    --  Neuroleptic 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.
    --  QT 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.
    --  Tardive 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.
    --  Metabolic 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.
        --  Hyperglycemia 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.
        --  Dyslipidemia: Undesirable alterations have been observed in patients
            treated with atypical antipsychotics.
        --  Weight Gain: Weight gain has been observed with atypical
            antipsychotic use. Clinical monitoring of weight is recommended.
    --  Orthostatic 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.
    --  Leukopenia, 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.
    --  Hyperprolactinemia: 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.
    --  Potential 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.
    --  Seizures: 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.
    --  Administration: For intramuscular injection only. Care should be taken
        to avoid inadvertent injection into a blood vessel.

    --  Drug 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.
    --  Pregnancy/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(®).
    --  Commonly 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.)

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SOURCE Janssen Research & Development, LLC


Source: PR Newswire



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