Last week, the U.S. Food and Drug Administration (FDA) handed down two new approvals for Invega (paliperidone), an atypical antipsychotic medication, for the treatment of schizoaffective disorder, and a long-acting (once-monthly) form of the drug (Invega Sustenna [paliperidone palmitate]) for schizophrenia.
According to the manufacturer, the extended-release injectable suspension, Invega Sustenna, is the first once-monthly, long-acting, injectable atypical antipsychotic approved in the U.S. for schizophrenia.
Invega (paliperidone) extended-release tablets were approved for the acute treatment of schizoaffective disorder either as monotherapy or adjunctive therapy to mood stabilizers and/or antidepressants. Invega was originally approved in 2006 for the treatment of schizophrenia.
Differentiating schizoaffective disorder from schizophrenia or a mood disorder can be difficult. Patients with schizoaffective disorder experience the psychosis characteristic of schizophrenia, such as hallucinations or delusions, as well as symptoms of mania and/or depression. Among people who frequently use mental health services, schizoaffective disorder may account for approximately 24 percent of cases.
“Schizoaffective disorder can be challenging to diagnose because of the broad range of symptoms patients experience,” said Nina Schooler, Ph.D., SUNY Downstate Medical Center. “The approval of Invega is exciting as it is the only antipsychotic treatment proven in double-blind, randomized, placebo-controlled trials to be efficacious with a demonstrated tolerable safety profile treating both the psychotic and affective symptoms present in this understudied population.”
The approval is based on two international, randomized, double-blind, placebo-controlled studies of patients with an established diagnosis of schizoaffective disorder, who were experiencing acute symptoms. In the first six-week study, patients received flexible doses of Invega (3-12 mg once daily). In the other study, patients were assigned to one of two dose levels of Invega: 6 mg with the option to reduce to 3 mg, or 12 mg with the option to reduce to 9 mg. In addition to study medication, subjects were permitted to receive concomitant treatment with a mood stabilizer and/or antidepressant, provided these medications had been given at a stable dose within 30 days of screening. Approximately half the subjects enrolled received ongoing treatment with a mood stabilizer and/or antidepressant during the studies. The most commonly used mood stabilizers were valproate and lithium. The most commonly used antidepressants were SSRIs and SNRIs.
Efficacy was evaluated using the positive and negative symptom scale (PANSS), a validated multi-item inventory composed of five factors to evaluate positive symptoms, negative symptoms, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression. As secondary outcomes, mood symptoms were evaluated using the Hamilton Depression Rating Scale (HAM-D-21) and the Young Mania Rating Scale (YMRS).
The Invega group in the flexible-dose study (dosed between 3 and 12 mg/day, mean modal dose of 8.6 mg/day) and the higher dose group of Invega in the 2 dose-level study (12 mg/day with option to reduce to 9 mg/day) were each superior to placebo in the PANSS. Numerical improvements in mood symptoms were also observed, as measured by the HAM-D-21 and YMRS. In the lower dose group of the 2 dose-level study (6 mg/day with option to reduce to 3 mg/day), Invega was not significantly different from placebo as measured by the PANSS.
The most common adverse events (incidence greater than or equal to 5% and at least twice that for placebo) were extrapyramidal symptoms, somnolence, dyspepsia, constipation, weight increase, and nasopharyngitis.
The approval of Invega Sustenna for schizophrenia was 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. During the double-blind phase of the study, fewer patients treated with INVEGA SUSTENNA experienced a relapse (10%) compared with those in the placebo group (34%).
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.
Source: Johnson & Johnson news releases