Denovo Biopharma and Orygen have partnered to launch a phase 2 trial investigating pomaglumetad methionil (DB103), a glutamate-targeting therapy, for treating first-episode psychosis (FEP) and clinical high risk (CHR) of psychosis in young adults. The open-label, feasibility trial will be led by Professor Patrick McGorry, MD, with Orygen in Parkville, Australia serving as the research sponsor.
Study Design and Parameters
The trial will enroll youth aged 18 to 25 years with insufficient response to a single first-line antipsychotic treatment in patients with FEP, or failure of remission of CHR-positive symptoms and functional recovery in patients with CHR. Participants will receive 2 daily doses of pomaglumetad methionil 40 mg over 12 weeks. Investigators will assess safety, tolerability, and acceptability, along with the drug’s ability to reduce total symptomatology and dysfunction. The Royal Melbourne Hospital Human Research Ethics Committee approved the study under Project 2024.289.
Drug Mechanism and Rationale
Pomaglumetad methionil is described as a first-in-class psychiatric drug that selectively acts on the glutamic acid mGlu2/3 receptor with no cross-reaction with other central nervous system receptors. According to McGorry, this mechanism may address shortcomings of existing antipsychotics, such as weight gain and prolactin elevation, while targeting the glutamate system’s role in psychotic disorders.
“Despite the introduction of antipsychotic medications over a decade ago, treatment options for a substantial minority of young patients with FEP or CHR of psychosis remain limited,” McGorry stated. He added that pomaglumetad “may be uniquely effective” in fulfilling this unmet medical need given its excellent safety profile.
Previous Research Context
According to Denovo CEO Wen Luo, PhD, while pomaglumetad “did not achieve statistically significant efficacy in a broad schizophrenia patient study, a subset of patients early in disease exhibited significantly greater improvement.” Previous research showed the drug demonstrated promise in preclinical work but failed to show efficacy in clinical trials, though it may be effective in certain patient populations. Research on pomaglumetad methionil as an adjunctive treatment with atypical antipsychotics was discontinued over a decade ago due to lack of efficacy.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.psychiatrictimes.com/view/denovo-biopharma-partners-with-orygen-for-phase-2-study-of-pomaglumetad-methionil-in-treating-psychosis