FDA Approves Johnson & Johnson Pharmaceutical Research & Development, LLC (CA)'s (JOBS) INVEGA(R) SUSTENNA(TM) for the Acute and Maintenance Treatment of Schizophrenia

TITUSVILLE, N.J., July 31 /PRNewswire/ -- The U.S. Food and Drug Administration today approved INVEGA® SUSTENNA(TM) (paliperidone palmitate) extended-release injectable suspension for the acute and maintenance treatment of schizophrenia in adults. It is the first once-monthly, long-acting, injectable atypical antipsychotic approved in the U.S. for this use. Janssen®, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc, will market INVEGA SUSTENNA in the U.S.

An estimated one percent of the world's population suffers from schizophrenia - a brain disorder that impairs a person's ability to think clearly, relate to others, and distinguish between reality and imagination. While there is no cure for schizophrenia, the symptoms and the risk of relapse (an exacerbation of symptoms) can be managed in most patients with appropriate treatment that includes continuous, long-term therapy with antipsychotic medications.(1)

Unfortunately, 80 percent of patients with schizophrenia experience at least one relapse within five years of diagnosis(2), and the risk for relapse in patients can substantially increase as a result of non-adherence.(2) Research shows that many patients treated with an oral atypical antipsychotic miss taking medication for about one-third of the year (110 days).(3) Therefore, it is critical for healthcare professionals to ensure that patients are following their treatment plans in order to help reduce the risk of relapse, because prognosis and outcome can progressively decline with each successive relapse.(4)

"Inconsistent compliance with medications is arguably one of the single greatest impediments to managing the symptoms of schizophrenia and delaying the time to relapse," said Henry A. Nasrallah, M.D., a clinical investigator who worked on the INVEGA SUSTENNA clinical trials, and a Professor of Psychiatry and Neuroscience and Director of the Schizophrenia Research Program at the University of Cincinnati College of Medicine. "The approval of once-monthly INVEGA SUSTENNA will provide healthcare professionals with a treatment option that is, at the same time, a definitive monitoring tool for uninterrupted medication compliance, which may help optimize clinical outcomes in schizophrenia."

The approval is based on four acute symptom control studies and a longer-term maintenance study that compared INVEGA SUSTENNA to placebo. INVEGA SUSTENNA was superior to placebo in improving positive and negative syndrome scale (PANSS) total scores in the acute treatment trials and significantly delayed time to relapse vs. placebo in the longer-term maintenance study.

The most recent acute symptom control study was a multi-center, randomized, placebo-controlled, double-blind, parallel-group study (n=636). All patients received a dose of 234 mg on Day 1 in the deltoid muscle. From Day 8 and monthly thereafter, patients were assigned to one of three fixed doses of INVEGA SUSTENNA for a period of 13 weeks. The primary endpoint of this study was the change in total PANSS score from baseline to endpoint. Each of the three additional acute treatment studies involving INVEGA SUSTENNA met its primary endpoint of significantly improving PANSS scores relative to placebo.

The efficacy of INVEGA SUSTENNA in maintaining symptomatic control in schizophrenia was evaluated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study (n=410). Time-to-first relapse - the primary endpoint of the study - was significantly longer for patients receiving INVEGA SUSTENNA compared with placebo-treated patients (P<0.0001). During the double-blind phase of the study, fewer patients treated with INVEGA SUSTENNA experienced a relapse (10% [n=15/156]) compared with those in the placebo group (34% [n=53/156]).

Because maintenance of efficacy was demonstrated, the trial was ended early. Patients on INVEGA SUSTENNA experienced a significant delay in time to relapse compared to placebo. Patients on placebo had a 3.6 fold higher incidence of experiencing relapse versus INVEGA SUSTENNA. As such, INVEGA SUSTENNA has the potential to be of tremendous benefit for physicians, caregivers and patients.

In clinical trials, the most common adverse events (incidence greater than or equal to 5% and occurring at least twice as often as placebo) were injection site reactions, somnolence/sedation, dizziness, akathisia and extrapyramidal disorder.

"INVEGA SUSTENNA provides healthcare professionals the opportunity to rethink their overall approach to how they treat schizophrenia by using long-acting therapies," said Husseini Manji, M.D., F.R.C.P.C., Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Pharmaceutical Research & Development. "The approval of INVEGA SUSTENNA demonstrates our commitment to providing valuable novel therapies for schizophrenia. INVEGA SUSTENNA has a demonstrated safety profile that can help healthcare professionals address the issue of medication adherence and can also help many patients delay the time to relapse."

Visit http://www.INVEGASUSTENNA.com for full prescribing information.

IMPORTANT SAFETY INFORMATION FOR INVEGA® SUSTENNA(TM)

INVEGA® SUSTENNA(TM) is not approved for the treatment of dementia-related psychosis in elderly patients. Elderly patients who were given oral antipsychotics like INVEGA® SUSTENNA(TM) in clinical studies for psychosis caused by dementia (memory problems) had a higher risk of death.

Neuroleptic Malignant Syndrome (NMS) is a rare, but serious side effect that could be fatal and has been reported with INVEGA® SUSTENNA(TM) and similar medicines. Call the doctor right away if you develop symptoms such as a high fever, rigid muscles, shaking, confusion, sweating more than usual, increased heart rate or blood pressure, or muscle pain or weakness. Treatment should be stopped if you are being treated for NMS.

One risk of INVEGA® SUSTENNA(TM) is that it may change your heart rhythm. This effect is potentially serious. You should talk to your doctor about any current or past heart problems. Because these problems could mean you're having a heart rhythm abnormality, contact your doctor IMMEDIATELY if you feel faint or feel a change in the way that your heart beats (palpitations).

Tardive Dyskinesia (TD) is a rare, but serious and sometimes permanent side effect reported with INVEGA® SUSTENNA(TM) and similar medicines. Call your doctor right away if you start to develop twitching or jerking movements that you cannot control in your face, tongue, or other parts of your body. The risk of developing TD and the chance that it will become permanent is thought to increase with the length of therapy and the total dose received. This condition can also develop after a short period of treatment at low doses but this is less common. There is no known treatment for TD but it may go away partially or completely if the medicine is stopped.

High blood sugar and diabetes have been reported with INVEGA® SUSTENNA(TM) and similar medicines. If you already have diabetes or have risk factors such as being overweight or a family history of diabetes, blood sugar testing should be done at the beginning and during the treatment. The complications of diabetes can be serious and even life-threatening. Call your doctor if you develop signs of high blood sugar or diabetes, such as being thirsty all the time, having to urinate or "pass urine" more often than usual, or feeling weak or hungry.

Weight gain has been observed with INVEGA® SUSTENNA(TM) and other atypical antipsychotic medications. If you notice that you are gaining weight, please notify your doctor.

INVEGA® SUSTENNA(TM) and similar medicines can raise the blood levels of a hormone called prolactin and blood levels of prolactin remain high with continued use. This may result in some side effects including missed menstrual periods, leakage of milk from the breasts, development of breasts in men, or problems with erection.

Some people may feel faint, dizzy, or may pass out when they stand up or sit up suddenly. Be careful not to get up too quickly. It may help if you get up slowly and sit on the edge of the bed or chair for a few minutes before you stand up. These symptoms may decrease or go away after your body becomes used to the medicine.

INVEGA® SUSTENNA(TM) and similar medicines have been associated with decreases in the counts of white cells in circulating blood. If you have a history of low white blood cell counts or have unexplained fever or infection, then please contact your doctor right away.

INVEGA® SUSTENNA(TM) can make some people feel dizzy, sleepy, or less alert. Until you know how you are going to respond to INVEGA® SUSTENNA(TM), be careful driving a car, operating machines, or doing things that require you to be alert.

INVEGA® SUSTENNA(TM) should be used cautiously in people with a seizure disorder, who have had seizures in the past, or who have conditions that increase their risk for seizures.

Call your doctor right away if you start thinking about suicide or wanting to hurt yourself.

In a study of people taking INVEGA® SUSTENNA(TM) common side effects in the treatment of schizophrenia were reactions at the injection site, sleepiness, dizziness, feeling of inner restlessness, and abnormal muscle movements, including tremor (shaking), shuffling, uncontrolled involuntary movements, and abnormal movements of the eyes.

This is not a complete list of all possible side effects. Ask your doctor or treatment team if you have any questions or want more information.

If you have any questions about INVEGA® SUSTENNA(TM) or your therapy, talk with your doctor.

About INVEGA® SUSTENNA(TM)

INVEGA SUSTENNA is approved for the acute and maintenance treatment of schizophrenia. It is the first once-monthly, long-acting, injectable atypical antipsychotic approved for this use in the U.S. INVEGA SUSTENNA is available in milligrams (mg) of paliperidone palmitate in dose strengths of 39 mg, 78 mg, 117 mg, 156 mg and 234 mg. Please be aware that clinical trial data presented at medical meetings were often reported as milligram equivalents (mg eq.) to paliperidone. Each dose of paliperidone palmitate is equivalent to a specific dose of paliperidone (39 mg, 78 mg, 117 mg, 156 mg and 234 mg of paliperidone palmitate is equivalent to 25 mg, 50 mg, 75 mg, 100 mg and 150 mg of paliperidone, respectively).

The pre-filled syringes require no reconstitution or refrigeration. Patients initiate treatment with two injections administered in the deltoid muscle one week apart (Day 1 at 234 mg and Day 8 at 156 mg), followed by injections every month thereafter administered in either the deltoid or gluteal muscle.

INVEGA SUSTENNA was developed utilizing Elan Drug Technologies' proprietary NanoCrystal® Technology. Using this technology increases the rate of dissolution and enables the formulation of an aqueous suspension for once-monthly intramuscular administration. INVEGA SUSTENNA is manufactured by Janssen, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc, in the U.S.

About J&JPRD

INVEGA SUSTENNA was developed by Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD), a member of the Johnson & Johnson family of companies, the world's most broadly-based producer of health care products. J&JPRD is headquartered in Raritan, N.J., and has facilities throughout Europe, the United States, and Asia. J&JPRD is leveraging drug discovery and drug development in a variety of therapeutic areas, including CNS, Internal Medicine, and Oncology, to address unmet medical needs worldwide. More information can be found at http://www.jnjpharmarnd.com.

About Janssen

Janssen, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc, is based in Titusville, N.J., and is the only large pharmaceutical company in the U.S. dedicated solely to mental health. It currently markets prescription medications for the treatment of schizophrenia, bipolar mania, schizoaffective disorder and the treatment of symptoms associated with autistic disorders. Ortho-McNeil-Janssen Pharmaceuticals, Inc is a member of the Johnson & Johnson family of companies. For more information about Janssen, visit http://www.janssen.com/.

About NanoCrystal® Technology and Elan Drug Technologies

INVEGA SUSTENNA utilizes the NanoCrystal® Technology, which is a proprietary technology developed by Elan Drug Technologies through Elan Pharma International Limited and other Elan affiliates. NanoCrystal® Technology is a registered trademark of Elan Pharma International Limited, Ireland, a subsidiary of Elan Corporation plc (NYSE: ELN - News). The NanoCrystal® Technology is a proven, robust, drug optimization technology, enabling solubility for many poorly water-soluble compounds. More information is available at www.elandrugtechnologies.com.

(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. 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 Janssen and/or Johnson & Johnson's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these 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 28, 2008. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither Janssen nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)

(1) Keith SJ, Kanke JM. Journal of Clinical Psychiatry 2003; 64:1308-15 (2) Robinson D, Woerner MG, Alvir JM, et al. Predictors of relapse following response from a first episode of schizophrenia or Schizoaffective Disorder. Archives of General Psychiatry 1999; 56:241-247 (3) Kane, JM. Review of Treatments That Can Ameliorate Nonadherence in Patients With Schizophrenia. Journal of Clinical Psychiatry 2006; 67 (suppl 5): 9-14 (4) Wyatt, RJ. Neuroleptics and the natural course of schizophrenia. Schizophrenia Bulletin 1991; 17:325-51

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