Actinogen Medical Limited's drug Xanamem (emestedastat), a novel therapy targeting dysregulated brain cortisol, has received a significant boost with the World Health Organization (WHO) granting it the nonproprietary name 'emestedastat'. This recognition coincides with the advancement of the XanaMIA Phase 2b/3 clinical trial for Alzheimer's disease and the publication of a peer-reviewed article supporting the drug's dosing strategy.
The WHO's designation of 'emestedastat' acknowledges Xanamem as a first-in-class 11β-HSD1 enzyme inhibitor. This classification highlights Actinogen's pioneering role in developing therapies that control brain cortisol levels, potentially offering clinically meaningful benefits for patients with Alzheimer's disease (AD) and major depressive disorder (MDD).
XanaMIA Trial Progress and Design
The XanaMIA phase 2b/3 clinical trial, a double-blind, placebo-controlled study, is currently enrolling 220 participants with mild to moderate AD and elevated levels of the blood biomarker pTau181 in the USA and Australia. The trial is designed to assess the efficacy of Xanamem 10 mg daily over a 36-week treatment period. The primary endpoint is the Clinical Dementia Rating – Sum of Boxes (CDR-SB) scale, a standard measure in AD trials. Interim results from the first 100 participants are expected in Q4 2025, with final results anticipated in H2 2026.
Clinical Pharmacology Supports 10 mg Dose
Actinogen also announced the publication of a peer-reviewed article in Clinical Pharmacology in Drug Development, which confirms the utility of the 10 mg daily dose of Xanamem being used in the XanaMIA trial and trials for major depressive disorder. The review highlights the value of using central pharmacodynamics, including positron emission tomography (PET) and computerized cognitive testing, to refine dose selection. Data suggested that Xanamem doses of 10 mg or even 5 mg daily may be sufficient to adequately inhibit its 11β-HSD1 enzyme target.
Dr. Dana Hilt, Actinogen’s Chief Medical Officer, stated, “The detailed and thorough drug development steps taken by Actinogen to confirm the target dose range of ≤ 10 mg daily demonstrate the value of careful and stepwise clinical pharmacology testing and use of measures of direct brain effects.”
Preparing for Commercialization
Actinogen is actively preparing for the potential commercialization of Xanamem. These initiatives include engaging with the FDA to define marketing approval criteria for AD and MDD and holding discussions with potential co-development partners. The company is also scaling up drug substance manufacturing and expanding its patent portfolio to extend commercial protection into the 2040s.
Dr. Steven Gourlay, Actinogen's CEO and Managing Director, expressed confidence in Xanamem's potential, stating, "Based on the clinical benefits seen in phase 2 trials with the 10mg daily dose of emestedastat in both AD and MDD, we have a high level of confidence in the likely positive outcomes of current and future trials in these and other diseases."
