Regulatory Decision Summary for INVEGA SUSTENNA

Based on the data from the single, Phase IIIb, randomized, double-blind, placebo-controlled, multicentre, international clinical trial in patients diagnosed with schizoaffective disorder, which utilized a randomized withdrawal design, the sponsor has provided evidence of the efficacy and safety of Invega Sustenna for maintenance treatment of patients with schizoaffective disorder. Given that the efficacy in schizoaffective disorder has previously been demonstrated for oral paliperidone extended release in two randomized, placebo controlled trials, a single pivotal clinical trial in schizoaffective disorder with paliperidone palmitate was deemed acceptable to support the proposed schizoaffective disorder indication for this product.

In patients that were first stabilized on Invega Sustenna during 6 months of open-label treatment, the time to relapse with symptoms of schizoaffective disorder was statistically significantly longer for patients that continued treatment with Invega Sustenna for up to 15 months compared to patients that were switched to placebo during the double-blind phase of the trial.

The safety of Invega Sustenna in patients with schizoaffective disorder was generally consistent with what has been observed in patients with schizophrenia in short-term and long-term clinical trials and was consistent with what has been observed in patients with schizoaffective disorder that were treated in short-term clinical trials with oral paliperidone extended release (Invega). Although the acute treatment phase of the study was not controlled and the efficacy of paliperidone palmitate for acute treatment was not systematically evaluated in this patient population, the efficacy of oral paliperidone extended release has been demonstrated for acute treatment of patients with schizoaffective disorder. During the double-blind phase, relapses due to psychotic, manic, and depressive symptoms were reported in both treatment groups but at higher rates in patients that switched to placebo than in patients that continued paliperidone palmitate treatment in the double-blind period of the study. Therefore, based on the available data at this time, the benefit-harm for the treatment of patients diagnosed with schizoaffective disorder with Invega Sustenna can be considered acceptable when the product is used as indicated for this patient population under the conditions of use described in the revised Invega Sustenna Product Monograph.

Uncertainty

The Diagnostic and Statistical Manual of Mental Disorders (DSM), 4th edition (DSM-IV) criteria were used to select patients for the Invega Sustenna schizoaffective disorder study, but the study inclusion criteria also indicated that patients had to have a lifetime and current diagnosis of schizoaffective disorder. This incorporates what may be the most important change to the schizoaffective disorder diagnostic criteria made in the DSM, 5th edition (DSM-V) to improve the reliability, validity and temporal stability of the diagnosis. Therefore, the sponsor attempted to ensure that the diagnosis of patients included in the study may at least be temporally stable. At this time, however, it remains to be determined whether the diagnosis of schizoaffective disorder will be improved by the changes made in the DSM-V.

Second generation antipsychotics are the mainstay of pharmacotherapy for schizoaffective disorder because these patients have psychotic symptoms that need to be managed and these drugs are known to be effective for this purpose. Although Invega and Invega Sustenna may be the only second generation antipsychotics that have been evaluated in defined populations of patients diagnosed with schizoaffective disorder, it is uncertain whether a specific indication for Invega Sustenna for treatment of schizoaffective disorder would necessarily address a specific need for prescribers and patients.