A new psychotropic drug for treating adults with schizophrenia met its primary endpoint and was "generally well tolerated" in a phase 2a study, according to its developers, Sunovion Pharmaceuticals Inc. and PsychoGenics Inc.

The mechanism of action of SEP-363856 does not involve serotonin or dopamine-receptor antagonism and is therefore different from currently available antipsychotic agents, they explain in a news release announcing the results. 

Treatment for Schizophrenia

"For more than 60 years, the treatment of schizophrenia has focused on blocking dopamine receptors." Finding a schizophrenia medication that works outside of a direct action on the dopamine system would be highly desirable, and SEP-363856 may represent such a breakthrough, "Dr. Shitij Kapur, dean of the faculty of medicine, dentistry and health sciences at the University of Melbourne in Australia, commented in the release.

SEP-363856 has shown broad efficacy in animal models of psychosis and depression. The molecular targets responsible for the antipsychotic and antidepressant efficacy of SEP-363856 in pre-clinical models appear to include agonist activity in both the trace amine associated receptor-1 (TAAR1) and the serotonin (5-HT) 1A receptors.

The SEP 361-201 study was a four-week, double-blind, placebo-controlled trial involving 245 adults hospitalized with an acute exacerbation of schizophrenia. They were randomly allocated to SEP-363856 (50 mg or 75 mg once daily) or placebo. Dr. Antony Loebel, head of global clinical development at Sunovion, presented the data during a poster session December 13 at the American College of Neuropsychopharmacology (ACNP) annual meeting in Hollywood, Florida.

After four weeks, patients taking SEP-363856 showed statistically significant and clinically meaningful improvement in the Positive and Negative Syndrome Scale (PANSS) total score (primary outcome) compared with placebo (-17.2 vs. -9.7; P = 0.001, effect size = 0.45).

Treatment with SEP-363856 also led to significant improvements in several secondary outcomes, including overall illness severity as judged by the Clinical Global Impression-Severity (CGI-S) score (-1.0 vs. -0.5), PANSS positive subscale score (-5.5) vs. -3.9), PANSS negative subscale score (-3.1 vs. -1.6) and PANSS general psychopathology subscale score (-9.0 vs. -4.7). 

Safety and tolerability of SEP-363856 were generally similar to placebo. In particular, SEP-363856 was not associated with extrapyramidal symptoms, akathisia, or hyperprolactinemia, consistent with its non-D2-based mechanism of action, Dr. Loebel reported. 

"The results of the Phase 2 trial are consistent in showing improvement in positive and negative symptoms, without the traditional side effects associated with dopamine blockers," Dr. Kapur said in the release. "The results need to be replicated in further studies and broader populations, but, if these results hold, it could be a valuable advance for patients and health care providers, as well as a great new avenue for exploration of new scientific mechanisms for psychotic disorders . "

"Following the results of Study 361-201, Sunovion plans to advance the development of SEP-363856 as quickly as possible," Dr. Loebel told Reuters Health by email .SEP-363856 is also being studied for Parkinson's disease psychosis, with additional indications under consideration, the companies said.