Actinogen Completes Enrollment in Pivotal Alzheimer's Trial with 247 Participants
Key Insights
Actinogen Medical (search) has completed enrollment of 247 participants in its XanaMIA phase 2b/3 trial testing Xanamem for mild-to-moderate Alzheimer's disease, exceeding the original target of 220 participants.
The 36-week randomized, placebo-controlled trial will deliver topline results in November 2026, with an interim safety and efficacy analysis scheduled for late January 2026.
Xanamem represents a novel oral therapy targeting brain cortisol levels through 11β-HSD1 (search) enzyme inhibition, offering potential advantages in safety and ease-of-use compared to existing monoclonal antibody treatments.
Actinogen Medical (search) Limited has announced the completion of enrollment in its pivotal XanaMIA phase 2b/3 Alzheimer's disease trial, with the final 247th participant randomized and commencing treatment. The accelerated enrollment exceeded the company's original target of 220 participants, positioning the trial to deliver topline results in November 2026.
Novel Cortisol-Targeting Mechanism
Xanamem (emestedastat (search)) represents a first-in-class oral therapy designed to control elevated brain cortisol levels through selective inhibition of the 11β-HSD1 (search) enzyme. The drug targets regions of high 11β-HSD1 expression, particularly the hippocampus, without interfering with normal cortisol production by the adrenal glands. Chronically elevated cortisol is associated with Alzheimer's disease progression and is known to be toxic to brain cells.
Dr. Dana Hilt, Chief Medical Officer, emphasized the significant unmet medical need: "There remains an enormous unmet medical need for patients at all stages of Alzheimer's despite the recent availability of new monoclonal antibody therapies. Oral Xanamem has the potential to be a game-changer for Alzheimer's patients because of its safety, ease-of-use and potential efficacy advantages."
Trial Design and Patient Population
The XanaMIA trial employs a double-blind, placebo-controlled, parallel group design spanning 36 weeks of treatment. Participants with mild to moderate Alzheimer's disease and progressive disease receive either Xanamem 10 mg or placebo once daily. Patient selection is based on clinical criteria and confirmed by elevated levels of the pTau181 (search) blood biomarker, following data from a previous 34-patient analysis in the XanADu phase 2 trial.
The primary endpoint utilizes the internationally-recognized CDR-SB (Clinical Dementia Rating scale – Sum of Boxes), with the trial being conducted across sites in Australia and the United States. All participants will be eligible for active Xanamem treatment in an open-label extension phase beginning in Q1 2026.
Supporting Clinical Evidence
Actinogen has compiled evidence from four independent, placebo-controlled trials supporting the pivotal program. In the most significant finding, patients with mild Alzheimer's disease and elevated blood pTau181 (search) levels (n=34) demonstrated large benefits on the CDR-SB endpoint after 12 weeks of treatment with 10 mg daily, with trends toward benefit on additional endpoints including ADCOMs, MMSE, and executive function measures.
Additional supportive data includes durable trends toward benefit on depressive symptoms in a moderately-severe population (n=165), validating clinical brain activity of the 10 mg daily dose. Two cognition trials in cognitively normal older volunteers showed improvements in attention and working memory across doses of 5 mg, 10 mg, and 20 mg daily (n=30-40 per group in both trials).
Regulatory Timeline and Next Steps
A formal interim analysis of safety and efficacy futility will be conducted by an independent Data Monitoring Committee in late January 2026. The committee comprises independent clinical and statistical experts who will review unblinded data in a confidential process, including participants who will have completed the full 36-week treatment period.
CEO and Managing Director Dr. Steven Gourlay outlined the company's 2026 priorities: "In 2026 we will be conducting the formal interim analysis of the trial, interacting with the European Medicines Agency on the path to approval in the EU in Q2, and planning for the upcoming clinical and manufacturing programs."
Drug Development Profile
Xanamem has been studied in eight clinical trials with approximately 500 people treated to date, demonstrating a promising safety and efficacy profile. The drug has shown excellent brain target engagement in human brain PET studies, supporting its mechanism of action in controlling cortisol levels in critical brain regions.
The completion of enrollment represents a significant milestone for Actinogen Medical (search), an ASX-listed biotechnology company based in Sydney with operations spanning Australia and the United States. The company's focus on addressing the cortisol pathway in Alzheimer's disease offers a differentiated approach in a therapeutic area dominated by amyloid-targeting strategies.