FDA approves INVEGA treatment for schizophrenia

Apr 30 2007

The U.S. Food and Drug Administration (FDA) has approved INVEGA (paliperidone) Extended-Release Tablets, a new once-daily, atypical antipsychotic, for the long-term maintenance treatment of schizophrenia.

INVEGA is now indicated for both acute (short-term) and maintenance (long-term) treatment of schizophrenia.

The agency's latest approval for INVEGA is based on a long-term efficacy study that demonstrated a significant benefit in delaying the time to relapse of symptoms of schizophrenia. This study ended early because efficacy was clearly demonstrated in a planned interim analysis. In addition, this study further supports the proven safety and tolerability profile seen in prior short-term studies. INVEGA is marketed in the U.S. by Janssen, L.P.

"Findings from this clinical trial complement the data supporting the use of INVEGA in the acute treatment of schizophrenia and suggest that efficacy can be maintained for many patients," said George M. Simpson, MD, Professor of Research, Director Outpatient Clinic, Keck School of Medicine of the University of Southern California, and one of the study's investigators. "Physicians now have a once-daily treatment option that can help many patients reduce symptom severity and also help stabilize patients with longer-term use."

Janssen President Janet Vergis said the approval is another example of Janssen's exclusive commitment to mental health. "It is our hope that new treatment options, such as INVEGA, will help patients with schizophrenia cope with this debilitating disease."

This long-term study of INVEGA systematically examined patients over time, enrolling individuals with acute schizophrenia first into an 8-week initiation period of treatment with INVEGA (3mg-15mg flexibly dosed, with a 9mg starting dose), followed by a further 6-week stabilization phase, during which patients remained on their previous dose. These stabilized patients were then observed for recurrence of symptoms of schizophrenia in a randomized, double blind, placebo-controlled phase until they relapsed, discontinued or completed the trial (ranging from six to 331 days). This double-blind phase studied 207 patients (105 randomly assigned to INVEGA and 102 randomly assigned to placebo), 75 of whom experienced a recurrence (23 on INVEGA and 52 on placebo).

INVEGA was seen to be significantly more effective than placebo in helping schizophrenia patients maintain control of their symptoms, and in delaying the time to relapse of symptoms. The final analysis of the study showed that 48.5 percent in the placebo group were able to proceed without a recurrence of symptoms, while 77.9 percent of patients in the INVEGA group progressed without relapse of symptoms.

There were three treatment-emergent adverse events (TEAEs) *** during the double blind, controlled phase of the study that occurred at a rate greater than or equal to five percent in either treatment group. These TEAEs were psychosis (23% placebo, 7% INVEGA), insomnia (6% placebo, 5% INVEGA), and aggressive reaction (6% placebo, 1% INVEGA). Adverse events related to extrapyramidal symptoms (e.g., involuntary movements, tremors, and rigidity) were seen in seven percent of INVEGA-treated patients compared with three percent in the placebo group during the double-blind phase. The incidence of TEAEs leading to discontinuation during the double-blind phase of this longer- term trial was one percent for placebo and three percent for INVEGA.

INVEGA (paliperidone) Extended-Release Tablets is (now) approved for the acute and maintenance treatment of schizophrenia in the U.S.

Worldwide, it is estimated that 1 person in every 100 develops schizophrenia, one of the most serious types of mental illness. In the United States, there are currently 2,000,000 people with schizophrenia, with men and women affected equally. The disease is marked by positive symptoms (hallucinations and delusions) and negative symptoms (depression, blunted emotions, and social withdrawal), as well by disorganized thinking.

INVEGA was approved in December 2006, and was the first new prescription treatment for schizophrenia to be approved by the FDA since 2003. The once- daily oral medication is specifically designed to deliver paliperidone - the active ingredient derived from risperidone - through the innovative OROS(R) extended-release technology, demonstrating powerful efficacy and a proven safety and tolerability profile. INVEGA was discovered and jointly developed by Janssen, ALZA Corp. and Johnson & Johnson Pharmaceutical Research and Development, LLC.

Janssen, L.P., based in Titusville, N.J., is the only pharmaceutical company in the U.S. dedicated solely to mental health. The company currently markets prescription medications for the treatment of schizophrenia, bipolar mania, and irritability associated with autistic disorder. For more information about Janssen, L.P., visit www.janssen.com; for more information on INVEGA, visit www.INVEGA.com.

IMPORTANT SAFETY INFORMATION FOR INVEGA(TM)

Elderly Patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. INVEGA (paliperidone) is not approved for the treatment of patients with dementia-related psychosis.

The most common side effects that occurred with INVEGA were restlessness and extrapyramidal disorder (for example: involuntary movements, tremors and muscle stiffness).

One risk of INVEGA is that it may change your heart rhythm. This effect is potentially serious, and you should talk to your doctor about any current or past heart problems. Some medications interact with INVEGA. Please inform your healthcare professional of any medications or supplements that you are taking.

Neuroleptic Malignant Syndrome (NMS) is a rare and potentially fatal side effect reported with INVEGA and similar medicines. Call your doctor immediately if the person being treated develops symptoms such as high fever; stiff muscles; shaking; confusion; sweating; changes in pulse, heart rate, or blood pressure; or muscle pain and weakness. Treatment should be stopped if the person being treated has NMS.

Tardive Dyskinesia (TD) is a serious, sometimes permanent side effect reported with INVEGA and similar medications. TD includes uncontrollable movements of the face, tongue, and other parts of the 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 overall dose taken by the patient. This condition can develop after a brief period of therapy at low doses, although this is much less common. There is no known treatment for TD, but it may go away partially or completely if therapy is stopped.

INVEGA 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.

INVEGA and similar medications can raise the blood levels of a hormone known as prolactin, causing a condition known as hyperprolactinemia. Blood levels of prolactin remain elevated with continued use. Some side effects seen with these medications include the absence of a menstrual period; breasts producing milk; the development of breasts by males; and the inability to achieve an erection. There is no known connection between prolactin levels and side effects.

High blood sugar and diabetes have been reported with INVEGA and similar medications. If the person being treated has diabetes or risk factors such as being overweight or a family history of diabetes, blood sugar testing should be performed at the beginning and throughout treatment with INVEGA. Complications of diabetes can be serious and even life threatening. If signs of high blood sugar or diabetes develop, such as being thirsty all the time, going to the bathroom a lot, or feeling weak or hungry, contact your doctor.

People with narrowing or blockage of the gastrointestinal tract (esophagus, stomach or small or large intestine) should talk to their healthcare professional before taking INVEGA.

Some people taking INVEGA may feel faint or lightheaded when they stand up or sit up too quickly. By standing up or sitting up slowly and following your healthcare professional's dosing instructions, this side effect may be reduced or it may go away over time.

Extrapyramidal Symptoms (EPS) are usually persistent movement disorders or muscle disturbances, such as restlessness, tremors, and muscle stiffness. If you observe any of these symptoms, talk to your healthcare professional.

Inform your healthcare professional if you are pregnant or if you are planning to get pregnant while taking INVEGA. Do not breast-feed if you are taking INVEGA.

INVEGA may affect your driving ability; therefore, do not drive or operate machines before talking to your healthcare professional. Avoid alcohol while on INVEGA.

INVEGA may affect alertness and motor skills; use caution until the effect of INVEGA is known.

INVEGA may make you more sensitive to heat. You may have trouble cooling off, or be more likely to become dehydrated, so take care when exercising or when doing things that make you warm.

INVEGA should be swallowed whole. Tablets should not be chewed, divided, or crushed. Do not be worried if you see something that looks like a tablet in your stool. This is what is left of the tablet after all the medicine has been released.