APA House Call: SEP-363856 for Schizophrenia

John Krystal, MD

The 2020 American Psychiatric Association (APA) Annual Meeting was cancelled this year, with plans made to convert the world-leading psychiatry conference into a two-part virtual session and educational platform for attendees.In lieu of regular on-site coverage, HCPLive® will be running a series of interviews, insights, and reporting on topics that frequently headline the APA meeting—featuring familiar experts.

What would a novel-targeting schizophrenia drug mean for the field?

For the case of investigative candidate SEP-363856, it may mean a broader improvement of symptoms, without a sacrifice of safety.

New data from the randomized, controlled trial assessing the efficacy and safety of SEP-363856 in adults with schizophrenia show the Sunovion drug candidate reduced symptoms versus placebo over 4 weeks.

The findings show the non-dopamine D2-receptor-binding oral compound might provide significant benefit for schizophrenia symptoms from a mechanism that deviates from common antipsychotic therapies.

“SEP-363856 does not block the dopamine receptors themselves, so it has the possibly to produce benefit—maybe even more benefit—with a different profile of tolerability,” explained John Krystal, MD.

In an interview with HCPLive, Krystal, the chair of Psychiatry at Yale University, detailed the discovery of the oral compound, its animal-model benefits which inspired the assessment of schizophrenia care, and how the drug’s targeting of trace amine-associated receptor 1 (TAAR1) and 5-hydroxytrypatimine type 1A (5-HT1A) receptor differentiates the mechanism of care in patients.

“It seemed to do a lot better than placebo, and not block the dopamine D2-receptor,” Krystal said. “That makes it, hopefully, the first medication that we’ll have in our toolbox to treat schizophrenia that does not block the dopamine D2-receptor.”