Regulatory Decision Summary for Perseris

Risperidone is an atypical antipsychotic with an established safety and efficacy profile. Perseris is a long-acting formulation of risperidone which uses the Atrigel delivery system. The compound is injected subcutaneously to form a gelatinous deposit under the skin that provides a continuous supply of risperidone for 28 days. Perseris pharmacokinetic (PK) studies showed that the levels of exposure with doses of 90 milligrams (mg) or 120 mg are similar to the recommended oral doses of 3 or 4 mg daily, respectively, administered over the same period of time. Perseris differs from other long-acting risperidone formulations in that the drug reaches therapeutic exposure levels within hours after administration, reducing the need for daily treatments and titration during treatment initiation.

The efficacy of Perseris was determined in a single placebo-controlled, double-blind 8-week pivotal study. Adult (18-55 years of age) patients with schizophrenia experiencing acute exacerbation of their symptoms were treated with two Perseris injections of either 90 mg (number of subject (n) = 111) or 120 mg (n = 114); or placebo (n = 112). Both Perseris doses achieved a statistically significant and clinically meaningful improvement, compared to placebo on a validated and widely used measure for antipsychotic efficacy, the Positive and Negative Syndrome Scale (PANSS). A longer-term 12-month open-label, uncontrolled safety study was performed. While the results did not reveal any unexpected safety signals, the efficacy conclusions were limited due to the study design.

The safety profile of risperidone is generally in line with other atypical antipsychotics. In the pivotal study, the most common treatment emergent adverse events were weight increase, constipation, sedation/somnolence, pain in extremity, back pain, akathisia, anxiety, and musculoskeletal pain. Plasma elevations in glucose, lipids and prolactin were consistent with the known safety profiles of other atypical antipsychotics. The safety profile of Perseris in the longer-term study was consistent with the expected profile. Injection site reactions were very common, but generally mild, transient and similar between Perseris and placebo injections.

Given that the pivotal study included only non-elderly patients who received two Perseris injections, the consistency of drug exposure over multiple doses, the long-term efficacy and the effect on the elderly were uncertainties. Recommendations for close monitoring during the initial months of therapy were added to the Product Monograph (PM), to mitigate the concerns regarding exposure over multiple doses. In addition, the lack of information in the elderly was also added to the PM.

A Risk Management Plan (RMP) was provided and deemed acceptable.

Perseris demonstrated a benefit for schizophrenia patients with a risk profile consistent with other risperidone products. Given the benefit of monthly treatments in this population together with the known safety profile of risperidone, the benefit-harm-uncertainty profile of Perseris is considered favorable.