The Key Clinical Study Of The First Non-dopamine D2 Receptor Binding Drug SEP-363856 Was Successful!

- Mar 23, 2020-

Sunovion Pharma, a US subsidiary of Japan's Sumitomo Pharmaceuticals (Sunovion), recently announced the results of a 4-week key study SEP361-201 that evaluated TAAR1 agonist SEP-363856 in the treatment of schizophrenia, which has been published in the New England Journal of Medicine (NEJM). The article title is: A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia.


The study results showed that the SEP-363856 treatment group showed a significant improvement in the total score of the Positive and Negative Symptom Scale (PANSS) compared with the placebo group. In this study, the effects of SEP-363856 treatment group and placebo group on extrapyramidal symptoms, body weight, and other metabolic parameters (blood lipid, glycated hemoglobin, prolactin, etc.) were similar.


SEP-363856 is a TAAR1 agonist, which has been granted a breakthrough drug qualification (BTD) for the treatment of schizophrenia by the US FDA. The drug has the potential to become the first new type of treatment for schizophrenia without the combination of dopamine D2 receptors. Antipsychotic drugs.

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Published in NEJM is a 4-week, randomized, double-blind, parallel group, placebo-controlled, flexible dose, multi-center study conducted in adult patients with acute episodes of schizophrenia, evaluating the efficacy and safety of SEP-363856 Sex. In the study, patients were randomized in a 1: 1 ratio and received SEP-363856 (50 mg or 75 mg) or placebo once daily for 4 weeks. The primary endpoint was the change in the total score of the Positive and Negative Symptoms Scale (PANSS; range: 30 to 210 points; higher scores indicate more severe psychiatric symptoms) at week 4 of treatment. The study had 8 secondary endpoints, including changes from baseline in the Clinical Overall Impression-Severity Scale (CGI-S) and Concise Negative Symptoms Scale (BNSS) scores. In the study, a total of 120 patients were assigned to the SEP-363856 treatment group and 125 patients were assigned to the placebo group. The average total PANSS scores at baseline for the two groups were 101.4 and 99.7, respectively.


The results showed that in the fourth week of treatment, compared with the placebo group, the SEP-363856 once-daily elastic dose (50-75mg) treatment group positive and negative symptom scale (PANSS) total score (-17.2 vs -9.7; p = 0.001) has statistically and clinically significant improvements. Compared with the placebo group, the SEP-363856 treatment group also showed an improvement in the clinical overall impression-severity scale (CGI-S) (p <0.001). In addition, there were improvements in all major PANSS (positive, negative, and general psychopathology) subscales (p <0.02). Adverse events of SEP-363856 treatment included drowsiness and gastrointestinal symptoms. Throughout the study, SEP-363856 was well tolerated, and the total withdrawal rates of the SEP-363856 and placebo groups were comparable. The incidence of extrapyramidal symptoms and changes in blood lipid, glycated hemoglobin, and prolactin levels were similar in both groups.

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John Krystal, MD, co-author of the NEJM article and chairman and co-director of psychiatry at the Yale Clinical Research Center at Yale University School of Medicine, said: "These data represent an exciting step forward in schizophrenia research. Targeting TAAR1 is A new mechanism of action for the treatment of schizophrenia represents a brave and innovative method in the treatment of schizophrenia. Over the past 60 years, antipsychotic drugs combined with dopamine receptors have been the standard therapy for the treatment of schizophrenia. Despite their side effects, the key clinical research results released this time support the potential of SEP-363856 as a new treatment for schizophrenia, which has the potential to cause schizophrenia patients and their families, schizophrenia The public health burden has a significant positive impact. "


Schizophrenia (schizophrenia) is a chronic, severe, and often severely disabling mental illness that affects more than 23 million people worldwide. In the United States, there are about 2.4 million adult patients with schizophrenia, equivalent to one in 100 adults suffering from schizophrenia. The clinical manifestations of schizophrenia are diverse, and its characteristics include positive symptoms (such as hallucinations, delusions, unorganized thinking), negative symptoms (such as lack of emotions, social withdrawal, lack of spontaneity), cognitive impairment (memory, attention) And planning, organizational and decision-making capabilities). Acute episodes of schizophrenia are characterized by psychotic symptoms, including hallucinations and delusions, and often require hospitalization. The disease is chronic and lifelong, often accompanied by depression and the gradual deterioration of social function and cognitive ability.


SEP-363856 is a novel trace amine-related receptor 1 (TAAR1) agonist with serotonin 1A (5-HT1A) agonist activity and is currently being evaluated in patients with schizophrenia. SEP-363856 does not bind to dopamine 2 (D2) or serotonin 2A (5-HT2A) receptors, which are believed to mediate the effects of currently available atypical antipsychotic drugs. Currently, SEP-363856 is being studied in the DIAMOND phase III global development project for the treatment of schizophrenia, and Sumitomo Pharmaceuticals is also considering other indications for the drug. In the United States, the FDA granted SEP-363856 a breakthrough drug qualification (BTD) for the treatment of schizophrenia in May 2019.


Dr. Kenneth Koblan, Chief Scientific Officer of Sunovion, said: "These findings published in the New England Journal of Medicine show that SEP-363856 has the potential to be the first TAAR1 agonist to treat schizophrenia. Currently, there are more than 23 million people worldwide For patients with schizophrenia, SEP-363856 as an innovative method will provide these patients with a new treatment option. Sumitomo Pharmaceutical is committed to developing new treatment options for these patients and continues to study SEP-363856 to further evaluate its Clinical efficacy of schizophrenia and other neuropsychiatric diseases. "


As pointed out in the NEJM article, in the 6-month open-label extension study, SEP-363856 showed continuous improvement of efficacy indicators, including total PANSS score, CGI-S score, and short negative symptoms scale (BNSS) total Points, and seems to be safe and tolerable.