Study found INVEGA® SUSTENNA® once-monthly long-acting therapy delayed time to and reduced risk of relapse in individuals with schizoaffective disorder as monotherapy and adjunctive therapy

Janssen Pharmaceuticals, Inc., today announced the results of the company’s schizoaffective relapse prevention study of once-monthly atypical long-acting antipsychotic INVEGA^® SUSTENNA^® (paliperidone palmitate). The trial found INVEGA^® SUSTENNA^® met its primary endpoint of delayed time to and reduced risk of relapse compared to placebo as monotherapy and adjunctive therapy in patients with schizoaffective disorder. INVEGA^® SUSTENNA^® also showed significant efficacy in manic and depressive mood symptoms and psychosis, and improved and maintained patient functioning.

Results of the study were presented at the 167^th Annual Meeting of the American Psychiatric Association (APA) in New York City and support the filing of a supplemental New Drug Application (sNDA) later this month for the treatment of schizoaffective disorder for INVEGA^® SUSTENNA^®.

“Even though it is associated with a high risk of hospitalization, suicidality and substance abuse, schizoaffective disorder isn’t the subject of extensive research, leaving clinicians with a complex polypharmacy approach to treatment,” said David P. Walling, PhD, Chief Executive and Clinical Officer, Collaborative NeuroScience Network, Inc., Los Angeles. “Subject to FDA approval, INVEGA^® SUSTENNA^® has the potential to be an additional option as the only long-acting injection indicated to treat schizoaffective disorder.”

The 15-month, randomized, double-blind, placebo (PBO)-controlled, international study evaluated 334 adults (INVEGA^® SUSTENNA^®, n=164; PBO, n=170) who met the DSM-IV diagnosis of schizoaffective disorder experiencing an acute exacerbation of psychotic symptoms with prominent mood symptoms as determined by the Young Mania Rating Scale (YMRS) and/or Hamilton Depression Rating Scale (HAM-D-21). Prior to randomization, individuals were first stabilized with INVEGA^® SUSTENNA^® (78–234 mg) either as monotherapy or an adjunct to antidepressants or mood stabilizers during a 13-week, open-label, flexible-dose, lead-in period and then continued into a 12-week open label, fixed-dose stabilization period. Stable patients were then randomized to treatment with INVEGA^® SUSTENNA^® once every four weeks or placebo and evaluated until relapse, discontinuation or completion of the 15-month relapse prevention period.

Relapse was defined as psychiatric hospitalization or any intervention to prevent hospitalization due to worsening of symptoms; clinically significant self-injury, suicidal or homicidal ideation or violent behaviors; or worsening of schizoaffective symptoms.

INVEGA^® SUSTENNA^® significantly delayed time to relapse compared to placebo (P<0.001). A higher percentage of patients relapsed in the placebo group (57 patients, 33.5%) than in the INVEGA^® SUSTENNA^® arm (25 patients, 15.2%) with the risk of relapse being 2.49-fold higher in the placebo group (HR 2.49; 95% CI: 1.55-3.99; P<0.001).

“The symptoms of schizoaffective disorder are complex and disabling, and medications to manage symptoms associated with the disorder are limited. We’re excited the trial suggests INVEGA^® SUSTENNA^® demonstrates efficacy in managing these symptoms and look forward to filing the application for this indication later this month,” said Dong-Jing Fu, Director of Clinical Development at Janssen Scientific Affairs. “As the company that pioneered the development of atypical long-acting treatments for mental illness, we’re proud to continue our commitment to investigating effective treatment options for individuals living with mental illness.”

A decrease in the risk of relapse occurred regardless of whether INVEGA^® SUSTENNA^® was taken alone or with another medication in a subgroup analysis. The risk of relapse was 3.38 times higher in the placebo group when INVEGA^® SUSTENNA^® was taken alone (HR 3.38; 95% CI: 1.57-7.28; P = 0.002). The risk of relapse was 2.03 times higher in the placebo group when INVEGA^® SUSTENNA^® was taken in combination with antidepressants or mood stabilizers treatment (HR 2.03; 95% CI: 1.11-3.68; P = 0.021).

The risk in the placebo group was 2.93 times higher for relapse due to any mood symptom (95% CI: 1.70, 5.04; p<0.001); 3.62 times higher for relapse due to manic symptoms (95% CI: 1.32, 9.89; p=0.012); 3.12 times higher for relapse due to depressive symptoms (95% CI: 1.39, 6.98; p=0.006); 1.93 times higher for relapse due to mixed symptoms (95% CI: 0.65, 5.78; p=0.238); and 2.82 times higher for relapse due to psychotic symptoms (95% CI: 1.70, 4.67; p<0.001).

INVEGA^® SUSTENNA^® was superior to placebo in maintaining patient functioning as measured by the Personal and Social Performance (PSP) scale as a key secondary endpoint. A difference in PSP total score was observed in favor of INVEGA^® SUSTENNA^® (least squares mean [SE] 3.3 [1.33]; P = 0.014). PSP is a validated clinician-rated scale that measures a range of personal and social functioning activities.

In this study, adverse events occurring in greater than 5% of patients in either group included weight gain (8.5% in INVEGA^® SUSTENNA^® vs. 4.7% in placebo), insomnia (4.9% vs. 7.1%), worsening of schizoaffective disorder (3.1% vs. 5.9%), headache (5.5% vs. 3.5%) and nasopharyngitis, which is the common cold (5.5% vs. 3.5%). The most common (≥2%) movement disorders were akathisia (3.0% in INVEGA^® SUSTENNA^® vs. 1.8% in placebo) and tremor (1.2% vs. 2.4%). Thirteen percent (13.0%) in the INVEGA^® SUSTENNA^® group and 6.0% in the placebo group had ≥7% increase in body weight. Potentially prolactin-related adverse events were reported in 10.4% of patients in the INVEGA^® SUSTENNA^® group and 3.5% in the placebo group.

By study design, only INVEGA^® SUSTENNA^® responders were randomly assigned to the relapse prevention period. As a result, findings in this study population may not be generalizable to all patients with schizoaffective disorder in clinical practice.