Researchers from Sunovion Pharmaceuticals Inc. presented early clinical data for SEP-363856, a novel trace amine receptor 1 (TAAR1) agonist with serotonin 5-HT1A activity, being developed for the treatment of patients with schizophrenia.

The effects of SEP-363856 on negative symptoms of patients with schizophrenia were evaluated in an initial double-blind phase II study ( Identifier NCT02969382), followed by the subsequent 6-month open-label extension study ( Identifier NCT02970929). Patients with an acute exacerbation of schizophrenia were randomized to 4 weeks of flexible-dose treatment with SEP-363856 (50 or 75 mg; n = 120) or placebo (n = 125). Those who completed the 4-week study continued on to an open-label extension clinical trial, which consisted of 26 weeks of treatment with flexible daily doses (25, 50 or 75 mg) of SEP-363856.

Results from the initial 4-week trial demonstrated that treatment with SEP-363856 was associated with significant week 4 improvement in negative symptoms compared to placebo, as assessed by the Brief Negative Symptom Scale (BNSS) total score, and BNSS subscale scores for blunted affect, avolition, anhedonia, asociality, alogia and distress. Significant improvements were also observed using the Marder PANSS negative symptom factor, and the UPSM-DE and UPSM-NAA factors. In the open-label extension study, treatment with SEP-363856 resulted in additional mean improvement from the open-label baseline to week 26, on the BNSS total score, the PANSS negative subscale score, the Marder PANSS negative symptom factor, and the UPSM-DE and UPSM-NAA factors.

Overall, these findings demonstrate that short-term treatment with SEP-363856 leads to significant and robust improvement relative to placebo in negative symptoms of schizophrenia as assessed by multiple measures, with continued improvement in negative symptoms seen during 26 weeks of additional open-label treatment with SEP-363856. These observations suggest that agonism at the TAAR1 receptor by SEP-363856 can treat both positive and negative symptoms in schizophrenia without incurring adverse effects on movement, prolactin, weight, and metabolic parameters associated with first and second generation antipsychotic drugs