Australian company Actinogen Medical has announced that results from its Phase 2 proof-of-concept trial of XANAMEM (emestedastat) have been published in the British Journal of Psychiatry, reporting meaningful antidepressant activity in a population described as difficult to treat.
The randomised, double-blind, placebo-controlled study enrolled 165 to 167 participants with major depressive disorder and measurable cognitive impairment, most of whom were taking another antidepressant during the trial.
The trial used a six-week treatment period followed by four weeks of blinded follow-up.
The greatest antidepressant separation from placebo occurred at Week 10 during the blinded follow-up period. A similar benefit was observed in the subgroup of patients taking background widely used Selective Serotonin Reuptake Inhibitors.
The study also examined cognition and found no correlation between improvements in cognition and improvements in depressive symptoms; cognition improved in both XANAMEM and placebo groups, with a larger-than-expected placebo improvement and no evidence of a XANAMEM treatment effect on cognitive outcomes.
Professor Michael Berk, a co-author, commented on the findings, “These results are highly encouraging for the XANAMEM 10 mg daily dose that is also being used in the Alzheimer’s disease program. The trial demonstrates that the drug penetrates the brain, and there is a signal of clinically meaningful activity to improve depression symptoms in a difficult-to-treat MDD [major depressive disorder patient population. There remains a significant unmet medical need for therapies such as Xanamem that have a novel mechanism of action and can be safely combined with existing depression treatments.”
Dr Dana Hilt, Actinogen’s Chief Medical Officer, added, “Depressive symptoms also occur frequently in patients with Alzheimer’s disease. Antidepressant activity may be a useful feature of XANAMEM treatment for Alzheimer’s disease and help to improve well-being and quality of life in these patients. The first pivotal phase 2b/3 trial of XANAMEM in Alzheimer’s disease is due to report topline results in November 2026, including initial evaluation of its effects on psychiatric symptoms.”
XANAMEM’s mechanism is inhibition of the brain enzyme 11β-HSD1 to reduce intracerebral cortisol without affecting adrenal cortisol production, a strategy intended to address cortisol-related cognitive and mood effects.
