The U.S. Food and Drug Administration today approved Invega Sustenna (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.
Unfortunately, 80 percent of patients with schizophrenia experience at least one relapse within five years of diagnosis, and the risk for relapse in patients can substantially increase as a result of non-adherence. Research shows that many patients treated with an oral atypical antipsychotic miss taking medication for about one-third of the year (110 days). 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.
"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.