SAN FRANCISCO — SEP-363856, a novel psychotropic agent with a non-D2 mechanism of action, showed statistically significant and clinically meaningful symptom improvement in patients with schizophrenia, according to data from a 4-week study presented at the APA annual meeting.
SEP-363856 also demonstrated robust activity across positive, negative, depressive and general psychopathology symptoms, the results showed.
“For more than 60 years, schizophrenia treatment has focused on blocking dopamine receptors,” Robert Goldman, PhD, head of global clinical research & medical affairs at Sunovion, told Healio Psychiatry. “Given the unmet medical needs in the treatment of schizophrenia even with the availability of many D2 blocking therapies, new therapies with different mechanisms could lead to significant advances in standard of care.”
In this placebo-controlled, phase 2 clinical trial, the investigators examined the efficacy and safety of SEP-363856 in acutely symptomatic, hospitalized patients with schizophrenia. Participants were randomly assigned to receive 4-weeks of flexible-dose treatment with SEP-363856 (once daily, 50 mg or 75 mg).
Using repeated measures analysis, the researchers examined change in the Positive and Negative Syndrome Scale (PANSS) total score (primary endpoint) as well as the Clinical Global Impressions-Severity (CGI-S) score, PANSS subscale scores and the Brief Negative Symptom Scale (BNSS) total score (secondary endpoints).
Although the PANSS total scores were similar in the SEP-363856 group (n = 120) and the placebo group (n = 125) at baseline, analysis indicated a significantly greater reduction for SEP-363856 by week 4 on the total score (–17.2 vs. –9.7; P = .001), the positive subscale score (–5.5 vs. –3.9; P = .019), the negative subscale score (–3.1 vs. –1.6; P = .008) and the general psychopathology subscale score (–9.0 vs. –4.7; P < .001).
In addition, the SEP-363856 group had a greater reduction than the placebo group on the CGI-Severity score (–1 vs. –0.5; P < .001) and BNSS total score (–7.1 vs. –2.7; P < .001).
Overall, the tolerability and safety for SEP-363856 appeared to be similar to placebo, according to the abstract. Study completion rates were similar in both groups as were changes in weight, lipids, glucose and prolactin. Adverse events occurring at a higher rate on SEP363-856 than placebo included: somnolence (6.7% vs. 4.8%), agitation (5% vs. 4.8%), nausea (5% vs. 3.2%), diarrhea (2.5% vs. 0.8%), and dyspepsia (2.5% vs. 0%).
“Although the exact mechanism of action is unknown, SEP-363856 is believed to activate TAAR1 (trace amine-associated receptor 1) in addition to 5-HT1A (serotonin 1A) receptors,” Goldman said. “SEP-363856 has the potential to be the first agent for the treatment of schizophrenia that does not bind to dopamine 2 (D2) receptors.” – by Savannah Demko
Koblan KS, et al. SEP-363856 in the treatment of schizophrenia: A 4-week, randomized, placebo-controlled trial of a novel compound with a non-D2 mechanism of action. Presented at: APA Annual Meeting; May 18-23, 2019; San Francisco.
Disclosures: Goldman is an employee of Sunovion.