The European Commission, on 25 June 2007, granted marketing authorisation for INVEGA® (paliperidone prolonged-release tablets), a new atypical antipsychotic medication for the treatment of schizophrenia. This once daily medication is specifically designed to deliver paliperidone - the active ingredient in INVEGA® - through the innovative osmotic delivery system (OROS®) resulting in strong efficacy, a proven safety and tolerability profile and improved patient functioning.

Paliperidone prolonged-release tablets will be marketed in Europe by Janssen-Cilag. This approval represents another important milestone in the company's long-standing commitment to develop new and improved treatment options for severe mental illnesses.

"Paliperidone prolonged-release tablets are an important addition to the range of options available for people with schizophrenia," said Professor Siegfried Kasper, Professor of Psychiatry and Chairman of the Department of Biological Psychiatry at the Medical University of Vienna, Austria. "I am impressed with the significant improvement in patient functioning as measured by the Personal and Social Performance (PSP) scale. Improved functioning is of critical benefit in the treatment of schizophrenia, and provides evidence that patients, on average, can expect to experience an enhanced ability to carry out every day activities when successfully treated with this agent. The introduction of new medicines, such as paliperidone prolonged-release tablets, provides a broadened range of effective treatment options for physicians who are constantly striving to achieve better outcomes for their patients with limited tolerability trade-offs."

The decision of the European Medicines Agency (EMEA) to grant a marketing authorisation for paliperidone prolonged-release tablets in the European Union is based on efficacy, safety and long-term results of an extensive clinical development program that included: three six-week, placebo-controlled clinical studies involving more than 1,600 patients with acute schizophrenia in 23 countries, (1) a long-term (40 weeks) double blind, placebo-controlled study looking at prevention of symptom recurrence in 207 randomised patients (2) and another double blind, placebo-controlled study assessing safety and tolerability in 114 elderly patients suffering from schizophrenia.(3)

• In the six-week pivotal trials (1) paliperidone prolonged-release tablets significantly reduced the symptoms of schizophrenia as measured by the Positive and Negative Syndrome Scale (PANSS), a tool commonly used in schizophrenia research that measures the severity of positive, negative and general psychopathological symptoms. Symptom reduction was seen as early as day 4 after treatment initiation. Patient functioning also improved as measured by the Personal and Social Performance (PSP) scale, a validated clinician-rated scale that measures patients’ ability to function in their daily life in four areas of behaviour: socially useful activities, including work and study; personal and social relationships; self-care; and disturbing and aggressive behaviours. All doses showed significant and clinically relevant improvement versus placebo as measured by the PSP scale. Paliperidone prolonged-release tablets is the first treatment for schizophrenia to receive EMEA approval for inclusion of improved social functioning in the product labelling. These studies also showed paliperidone prolonged-release tablets being generally safe and well tolerated with extrapyramidal side effects and weight gain comparable to placebo at the recommended dose of 6 mg.
• The long-term study (2) showed that paliperidone prolonged-release tablets was significantly more effective than placebo in the prevention of symptom recurrence and that continued treatment was associated with maintained symptom control. This study also confirmed that paliperidone prolonged-release tablets, over the longer term, was generally safe and well tolerated.
• The study in elderly schizophrenia patients (3) 65 years of age showed that treatment with paliperidone prolonged-release tablets was effective and generally safe and well tolerated in this population which may be more vulnerable to side effects.

Paliperidone prolonged-release tablets is the first and only treatment for schizophrenia to use the osmotic delivery system (OROS®). The OROS® system delivers paliperidone, the active ingredient, in a consistent way over a 24-hour period, leading to a smooth release of the drug through the day with minimal peaks and troughs in plasma concentrations.

Paliperidone prolonged-release tablets is not extensively metabolised by the liver and is excreted largely unchanged through the kidneys. Therefore it is not expected to cause clinically important drug-drug interactions with drugs metabolised by the liver.

Treatment-emergent adverse events (4) (TEAEs) reported in 5% or more of subjects treated with paliperidone prolonged-release tablets and at least twice the placebo rate for at least one dose included akathisia (extreme restlessness) and extrapyramidal disorders (e.g. involuntary movement, tremors or rigidity). Discontinuation rates due to adverse events for all paliperidone prolonged-release tablets dose groups were low and comparable to placebo (5% for both placebo and for paliperidone prolonged-release tablets).

The recommended dose of paliperidone prolonged-release tablets is 6 mg once daily, administered in the morning, taken in a consistent manner with or without food. Patients can start at the recommended dose with no need for initial dose titration. Some patients may benefit from higher or lower doses in the recommended dose range of 3 mg to 12 mg once daily and, following clinical reassessment, the dose can be adjusted both up and down.

Schizophrenia is one of the most serious types of mental illness. It is relatively common and the prevalence is similar around the world; one person in every 100 will develop schizophrenia before they reach the age of 45, with men and women equally at risk.(5)

The disease is marked mainly by positive symptoms (e.g. hallucinations, delusions) and negative symptoms (e.g. blunted affect, emotional and social withdrawal, difficulties in abstract thinking) as well as by lack of judgment and insight.

About Janssen-Cilag
INVEGA® was developed by Johnson & Johnson Pharmaceutical Research and Development, L.L.C. INVEGA® is another important milestone in Janssen-Cilag's 50-year commitment to developing and marketing treatments for severe mental illnesses.

In the European Union countries, INVEGA® is approved for the treatment of schizophrenia and is marketed by Janssen-Cilag. The Janssen-Cilag companies have a long track record in developing and marketing treatments for central nervous system disorders, pain management, oncology, fungal infections and gastrointestinal conditions. Leading products include Concertaâ (for treatment of ADHD), Durogesicâ (pain management), Eprexâ (anemia), Parietâ (gastroenterology), Topamaxâ (epilepsy, migraine prevention), Reminylâ (Alzheimer's disease), Risperdalâ (schizophrenia, bipolar disorders, disruptive behaviour), Risperdalâ Constaâ (schizophrenia) and Velcadeâ (multiple myeloma).

More information can be found at www.janssen-cilag.com.

1. Meltzer H et al. Efficacy and Tolerability of Oral Paliperidone Extended-Release Tablets in the Treatment of Acute Schizophrenia: Pooled Data from Three 6-Week Placebo-Controlled Studies. Poster presented at USP & MHC 2006, 16-19 November 2006 , New Orleans, NY, USA
2. Kramer M et al. Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. Journal of Clinical Psychopharmacology. 27(1):6-14, 2007 Feb.
3. Tzimos A et al. 6-Week Placebo-Controlled Study of the Safety and Tolerability of Flexible Doses of Oral Paliperidone Extended-Release Tablets in the Treatment of Schizophrenia in Elderly Patients. Poster presented at USP & MHC 2006, 16-19 November 2006, New Orleans, NY, USA
4. A treatment-emergent adverse event is defined as any event not present prior to the initiation of the treatments or any event already present that worsens in intensity or frequency following exposure to the treatments.
5. American Psychiatric Association. "Practice Guideline for the Treatment of Patients with Schizophrenia" supplement to Am J Psychiatry 1997; 154, 4.