Australia-based Actinogen Medical announced positive interim findings from the ongoing Phase IIb XanaMIA trial evaluating Xanamem, an oral inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), in patients with mild to moderate Alzheimer’s disease, with an independent Data Monitoring Committee recommending continuation of the study without amendment. The company said the review found no safety concerns and supported the trial’s ongoing assessment of cognitive and functional outcomes, a development that sustains clinical momentum for a mechanism distinct from amyloid- and tau-targeted approaches.

Trial specifics

XanaMIA is a randomized, double-blind, placebo-controlled Phase IIb study designed to evaluate the safety and efficacy of once-daily oral Xanamem in approximately 247 adults with mild to moderate Alzheimer’s disease. Patients were randomized to receive Xanamem 10 mg or placebo over a 36-week double-blind treatment period, followed by an optional open-label extension. The trial’s primary endpoint is change from baseline in cognition as measured by standard clinical scales, with additional secondary endpoints assessing functional outcomes and neuropsychiatric symptoms.

According to Actinogen, the interim review was conducted after approximately 37% of the planned dataset had accrued, encompassing more than 130 patients with at least one post-baseline efficacy assessment. The Data Monitoring Committee reviewed unblinded safety and efficacy data and concluded that the trial could continue as planned, indicating no emerging safety signals or futility concerns at this stage. The company did not disclose numerical efficacy data from the interim analysis and cautioned that conclusions regarding clinical benefit will depend on the final dataset.

Actinogen said topline results from XanaMIA are expected in Q4 2026, with data anticipated to be presented at a scientific meeting and submitted for peer-reviewed publication. An open-label extension will allow eligible participants continued access to Xanamem while longer-term safety and exploratory outcomes are assessed.

Research context

Xanamem is a small-molecule inhibitor of 11β-HSD1, an enzyme that regulates the conversion of inactive cortisone to active cortisol in the brain. Elevated cortisol levels have been associated with hippocampal atrophy, synaptic dysfunction, and cognitive decline in Alzheimer’s disease. By selectively inhibiting 11β-HSD1, Xanamem is intended to reduce chronic cortisol exposure in key brain regions without suppressing systemic cortisol production, offering a non-immunomodulatory approach to disease modification. Xanamem remains unapproved globally and has not been disclosed as having any special regulatory designations from the US FDA.

The Alzheimer’s disease treatment landscape has shifted in recent years with the approval of amyloid-targeting monoclonal antibodies, including Leqembi (lecanemab) from Eisai and Biogen and Kisunla (donanemab) from Eli Lilly. However, uptake has been constrained by safety considerations, imaging requirements, and modest clinical effect sizes, leaving room for alternative mechanisms that target non-amyloid pathways.

Within cortisol and stress-pathway modulation, clinical competition remains limited but includes earlier-stage efforts to address neurodegeneration through glucocorticoid biology. Key competitors include:

• Asceneuron’s ASN90, an oral O-GlcNAcase inhibitor targeting tau pathology rather than cortisol, which completed Phase II studies in progressive supranuclear palsy and illustrates the broader push toward non-amyloid mechanisms.
• Corcept Therapeutics’ relacorilant, a selective glucocorticoid receptor modulator in development for neuropsychiatric and metabolic disorders, although not advanced specifically for Alzheimer’s disease.