The European Commission granted marketing authorization for INVEGA(TM) (paliperidone prolonged release tablets), an 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(R)). In clinical trials, INVEGA demonstrated significant efficacy as compared to placebo in helping many patients control the symptoms of schizophrenia, and it was generally well tolerated.
INVEGA (paliperidone prolonged release tablets) will be marketed in Europe by Janssen-Cilag. In the U.S., this product is marketed by Janssen, L.P. as INVEGA (paliperidone) Extended-Release Tablets. This approval represents another important milestone in the company's long-standing commitment to develop new treatment options for serious mental illnesses.
INVEGA is the first and only treatment for schizophrenia to receive marketing authorization in the EU that uses the osmotic delivery system (OROS(R)).
The decision of the European Medicines Agency to grant marketing authorization for INVEGA in Europe is based on efficacy and safety 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,(i) a longer-term (up to 40 weeks) double blind, placebo controlled study in 207 randomized patients(ii) examining time to relapse, and another double blind, placebo controlled study assessing safety and tolerability in 114 elderly patients suffering from schizophrenia.(iii).
The primary measure of efficacy was the Positive and Negative Syndrome Scale (PANSS), a tool commonly used in schizophrenia research that measures the severity of positive and negative symptoms and general psychopathology. The Personal and Social Performance Scale (PSP), a measure of functional improvement, as well as safety and tolerability assessments, were also included in the trials that supported the approval of INVEGA. The recommended dose of INVEGA is 6 mg per day, with a dose range of 3 mg to 12 mg per day depending on patient need.
Key findings of the program include:
· In three six-week clinical trials, INVEGA demonstrated statistically significant symptom improvement on the PANSS versus placebo across all doses investigated. INVEGA was also superior to placebo on the PSP in these trials. In a chronic treatment trial, adult patients with schizophrenia who were treated with INVEGA showed a significantly longer time to relapse compared to placebo.
· From the three six-week clinical trials, treatment-emergent adverse events(iv) (TEAEs) reported in 5% or more of subjects treated with INVEGA and at least twice the placebo rate for at least one dose included: akathisia (i.e. restlessness) and extrapyramidal disorder (e.g. involuntary movements, tremors or muscle stiffness).
· In the three six-week clinical trials, discontinuation rates due to TEAEs for all INVEGA dose groups were low and comparable to placebo (5% for placebo and for INVEGA: 2% for 3 mg, 6% for 6 mg, 4% for 9 mg, 5% for 12 mg).
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 in nearly equal numbers. The disease is marked by positive symptoms (hallucinations and delusions) and negative symptoms (depression, blunted emotions, and social withdrawal), as well as by disorganized thinking.
INVEGA was approved in the U.S. in December 2006, and was the first new prescription treatment for schizophrenia to be approved by the U.S. FDA since 2003. In April 2007, INVEGA was also approved by the FDA for the long-term maintenance treatment of schizophrenia. INVEGA was discovered and jointly developed by ALZA Corporation and Johnson & Johnson Pharmaceutical Research and Development, LLC.
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.