Landmark Study Shows Once-Monthly Long-Acting Therapy INVEGA® SUSTENNA® (paliperidone palmitate) Significantly Delayed Time to Relapse in Patients with Schizophrenia Compared to Daily Oral Antipsychotic
First prospective, randomized clinical trial to reflect context of “real world” issues in treating schizophrenia, including recent incarceration and substance abuse
Titusville, NJ, May 5, 2014 – Janssen Pharmaceuticals, Inc., today announced the results of its landmark PRIDE (Paliperidone Palmitate Research In Demonstrating Effectiveness) trial. PRIDE is the first prospective, randomized clinical trial to compare schizophrenia medications within the context of many “real world” issues in the treatment of schizophrenia, including some of the most challenging circumstances – recent incarceration and substance abuse.
“The PRIDE trial is significant as it is the first to examine the ‘real-world’ consequences of relapse for individuals with schizophrenia,” said Mark Lerman, MD, principal investigator and medical director at the Center for Psychiatric Research at Alexian Brothers Behavioral Health Hospital in Hoffman Estates, Illinois. “The findings indicate that treatment with once-monthly INVEGA® SUSTENNA® significantly delayed time to relapse, as well as reduced overall relapse, compared to the most commonly used treatments, even for patients facing some of the most challenging circumstances.”
INVEGA® SUSTENNA® showed statistical superiority against the primary endpoint, delaying relapse in patients with schizophrenia, as well as in reducing overall relapse, compared to the most commonly used treatments, daily oral antipsychotics (median 416 days vs. median 226 days; P = 0.011). The risk of relapse was 1.4 times higher (95% CI: 1.09, 1.88, P=0.011) in the oral group versus the INVEGA® SUSTENNA® group.
Results of the study will be presented at the 167th Annual Meeting of the American Psychiatric Association (APA) in New York City and support the filing of a supplemental New Drug Application (sNDA) later this year for a U.S. label update.
Continuity of treatment is an ongoing challenge among individuals with schizophrenia, particularly after release from an institution, and lack of access to consistent community care may lead some to cycle through jails or prisons. In addition to the impact on patients, these factors have created an increasingly large and costly problem for the U.S. healthcare system.
“We are pleased and proud to share the results of the PRIDE trial, an example of Janssen’s long-standing commitment to research and development to advance care for people living with schizophrenia,” said Lynn Starr, MD, director of clinical development, Janssen Pharmaceuticals. “The study further demonstrates that INVEGA® SUSTENNA® helps address a critical need for all individuals living with schizophrenia by delaying relapse, even for those patients typically excluded from clinical trials, such as those with a history of incarceration and substance abuse.”
The 15-month U.S. multicenter, prospective, randomized, open-label, event monitoring board-blinded, active-controlled study assessed as its primary endpoint the time to treatment failure, which is a subset of relapse. The endpoint was defined as any one of the following: psychiatric hospitalization; arrest/incarceration; suicide; treatment supplementation or discontinuation of antipsychotic medication because of inadequate efficacy, safety concerns or tolerability issues; or increased level of psychiatric services in order to prevent psychiatric hospitalization.
No new safety issues were observed during the study. The most commonly observed adverse events (AEs) were consistent with those listed in the current U.S. label, including injection site pain, insomnia, weight increase, akathisia, which is restlessness ranging from a feeling of inner distress to an inability to sit still, and anxiety. Among the trial participants, 53 (23.5%) of those taking INVEGA® SUSTENNA® and 9 (4.1%) of those taking oral antipsychotics reported a treatment-emergent prolactin-related AE. Incidence of specific movement disorders associated with antipsychotics was 23.9% in the INVEGA® SUSTENNA® group and 18.8% in the oral antipsychotic group. A ≥7% increase in weight affected 32.4% of subjects in the INVEGA® SUSTENNA® group and 14.4% in the oral antipsychotic group. The study AEs should be evaluated within the context of the trial design and study population.
The study was not powered to compare efficacy of INVEGA® SUSTENNA® with that of individual oral antipsychotics. As with any trial population, results may not be generalized to all persons with schizophrenia.
About the PRIDE Study
The study evaluated 444 adults who had been diagnosed with schizophrenia and were taken into custody by the criminal justice system at least twice in the previous two years, with at least one custody resulting in incarceration. In addition, participants must have been released from their most recent custody within 90 days of screening for the trial. During screening, the investigator and patient reviewed oral medications available in the study to eliminate medications that should not be selected based on the patient’s prior experience, as is typical in the “real world.” Participants were then randomized to either monthly INVEGA® SUSTENNA® (78-234 mg) or one of seven prescribed daily oral therapies that represent a vast majority of antipsychotic medications used in the U.S. They were aripiprazole, haloperidol, olanzapine, paliperidone, perphenazine, quetiapine and risperidone. PRIDE evaluated patients across 50 sites located in major U.S. cities as well as rural settings.
This study included an exploratory analysis that looked at time to relapse in the subset of patients who were active substance abusers versus those who were not substance abusers. This exploratory analysis showed that comorbid substance abuse was present in a substantial proportion of this study population and points to the negative impact of substance abuse on treatment outcomes of patients with schizophrenia, with the observed percentage of treatment failure in the substance abuse group (53.4%) higher than those who were not substance users (36.7%). All hazard ratios appeared to show benefit of INVEGA® SUSTENNA® compared with oral treatment in time to first treatment failure, although this finding did not reach statistical significance for subjects with substance abuse. Further analyses are needed to confirm these findings. This analysis was hypothesis-generating and designed to help guide future research; it was not designed to address the particular impact on individuals with schizophrenia in general.
Additional Janssen Research at APA
The results of several other studies conducted by Janssen will be presented at the APA meeting, including the results of a schizoaffective relapse prevention study that found INVEGA® SUSTENNA® significantly delayed time to and reduced risk of relapse compared to placebo as monotherapy and adjunctive therapy.
Schizophrenia is a complex brain disorder that affects three million American adults. The disease typically manifests as hallucinations, delusions, and disorganized thoughts and behavior. Because there are currently no physical or laboratory tests that diagnose this condition, schizophrenia is diagnosed by the presence of symptoms. Researchers have identified various risk factors for this disease, including heredity, brain damage, and environmental factors, such as social stress, isolation and drug use.
About Janssen Pharmaceuticals, Inc.
As a member of the Janssen Pharmaceutical Companies of Johnson & Johnson, Janssen Pharmaceuticals, Inc., is dedicated to addressing and resolving the major unmet medical needs of our time. Driven by our commitment to patients, healthcare professionals, and caregivers, we strive to develop sustainable and integrated healthcare solutions by working in partnership with all stakeholders on the basis of trust and transparency. Our daily work is guided by meeting goals of excellence in quality, innovation, safety, and efficacy in order to advance patient care.
Our company provides medicines for an array of illnesses and disorders in several therapeutic areas. For more information on Janssen Pharmaceuticals, Inc., visit us at www.JanssenPharmaceuticalsInc.com or follow us on Twitter at www.twitter.com/JanssenUS and on YouTube at www.YouTube.com/JanssenUS.
INVEGA® SUSTENNA® (paliperidone palmitate) is indicated for the treatment of schizophrenia. 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.
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/mm3) should discontinue INVEGA® SUSTENNA® and have their WBC followed until recovery.
Hyperprolactinemia: As with other drugs that antagonize dopamine D2 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 (≥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) at www.InvegaSustenna.com.
(This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995, including regarding product development. 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 Pharmaceuticals, Inc. or Johnson & Johnson. Risks and uncertainties include, but are not limited to, technological advances, new products and patents attained by competitors; challenges and difficulties inherent in new product development, including obtaining regulatory approvals; manufacturing difficulties or delays; and trends toward health care cost containment. A further list and description of risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 29, 2013 and in its subsequent reports on Form 10-Q and Form 8-K. 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 statements as a result of new information or future events or developments.)