Phase 2/3 Study Begins for Generalized Anxiety Disorder Agent

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The first patient has been randomized in a phase 2/3 clinical study evaluating ulotaront, a trace amine-associated receptor 1 (TAAR1) agonist with 5-HT1A agonist activity for the treatment of generalized anxiety disorder (GAD).¹ Ulotaront (also known as SEP-363856) is also being investigated in late-stage clinical studies for the treatment of schizophrenia and for the adjunctive treatment of major depressive disorder (MDD).^2,3

“Generalized anxiety disorder is a chronic condition characterized by excessive anxiety or worries, sleep disturbances, changes in appetite and impairment of social and occupational activities which can have a profound impact on nearly all aspects of an individual’s life,” said Armin Szegedi, MD, PhD, Senior Vice President and Chief Medical Officer at Sunovion. “Preliminary data from preclinical and clinical studies of ulotaront suggest an anxiety-reducing effect, which we aim to understand further in patients with GAD. We believe that ulotaront is a potentially important novel mechanism and therapeutic advance for the treatment of GAD and other serious mental health conditions.”

The multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study will evaluate ulotaront’s efficacy and safety in individuals living with GAD. Randomized into 2 treatment groups, a total of 434 participants will be randomized and will receive either ulotaront (SEP-363856, 50 to 75 mg/day) or placebo in a 1:1 ratio for 8 weeks. The primary endpoint is reduced anxiety symptoms, as measured from baseline in the Hamilton Anxiety Rating Scale (HAM-A) total score, compared with placebo at week 8.

“Research to date has established that TAAR1 regulates dopamine neurotransmission to keep dopamine concentrations within an ideal physiological range,” John J. Miller, MD, explained recently in Psychiatric Times. “TAAR1 receptor agonism decreases dopamine presynaptic release, hence preventing a hyperdopaminergic state, whereas TAAR1 antagonism increases dopamine release in hypodopaminergic states.”⁴

“With the expansion of ulotaront’s clinical development program to a third indication, we are making significant progress towards goals we set for codevelopment and cocommercialization with Sunovion to address areas of high unmet need for people living with serious mental illnesses,” said John Kraus, MD, PhD, Executive Vice President and Chief Medical Officer at Otsuka. “We believe that ulotaront has the potential to help those living with GAD safely and effectively manage their symptoms and we look forward to advancing the understanding of this innovative compound.”

In 2019, ulotaront was granted Breakthrough Therapy Designation by the US Food and Drug Administration for the treatment of schizophrenia. It is the first TAAR1 agonist to enter phase 3 clinical studies in adults and adolescents (aged 13 to 17 years) with schizophrenia, and the first TAAR1 agonist to enter phase 2/3 clinical studies in GAD and the adjunctive treatment of MDD.

References

1. Sunovion and Otsuka initiate clinical development of ulotaront for the treatment of generalized anxiety disorder. Sunovion. News release. April 26, 2023. https://news.sunovion.com/press-releases/press-releases-details/2023/Sunovion-and-Otsuka-Initiate-Clinical-Development-of-Ulotaront-for-the-Treatment-of-Generalized-Anxiety-Disorder/default.aspx

2. Kraus J. TAAR1 and the future of MDD treatment. Psychiatric Times. December 19, 2022. https://www.psychiatrictimes.com/view/taar1-and-the-future-of-mdd-treatment  

3. Kuntz L. Late-stage pipeline candidate looks promising for the treatment of schizophrenia. Psychiatric Times. May 3, 2021. https://www.psychiatrictimes.com/view/late-stage-pipeline-candidate-looks-promising-treatment-schizophrenia

4. Miller JJ. Rx evolution: pharmacological paradigms for the treatment of schizophrenia. Psychiatric Times. 2023;40(1).