Safety and Effectiveness of SEP-363856 in Schizophrenia: Results of a 6-month, Open-label Extension Study

Background: SEP-363856 is a novel non-D2 receptor antagonist, and preclinical data suggest that agonism at trace amine associated receptor 1 (TAAR1) and the serotonin 5-H1A receptor contributes to its efficacy. In a previous double-blind (DB), placebo-controlled study, SEP-363856 demonstrated significant efficacy in the treatment of an acute exacerbation of schizophrenia (Koblan et al, NEJM 2020; 82:1497-1506). The aim of this extension study was to evaluate the safety and effectiveness of longer-term treatment with SEP-363856.

Method: Patients who completed the 4-week, DB, placebo-controlled study of SEP-363856 were treated for 26 weeks with open-label (OL) SEP-363856 (25/50/75 mg/d). The primary outcomes were safety measures; effectiveness outcomes were secondary and included the PANSS total score.

Results: Altogether, 156 patients were treated in this extension study and 66.9% were 26-week completers. Reasons for discontinuation consisted of adverse event (11.5%), withdrawal of consent (10.2%), lack of efficacy (5.1%), and other (6.4%). Individual AEs with an incidence ‚â•5% were schizophrenia (12.2%), headache (11.5%), insomnia (8.3%), and anxiety (5.1%). No clinically meaningful changes were observed on movement scales. Mean month 6 change from DB baseline in weight was -0.3 kg. No clinically meaningful changes were observed at week 26 in metabolic laboratory parameters, or prolactin levels. Continued improvement from OL baseline to week 26 was observed on the PANSS total score (mean: -19.8).

Conclusion: Up to 26 weeks of treatment with SEP-363856 had minimal effects on weight, metabolic parameters, prolactin, or extrapyramidal symptoms. SEP-363856 was associated with continued improvement from open-label baseline in the PANSS total score.