Phase 2b/3 Alzheimer’s trial enrolment expected to reach 100 this quarter, triggering an interim analysis 6 months later
SYDNEY, April 30, 2025 (GLOBE NEWSWIRE) — Actinogen Medical Limited (ASX: ACW) announces that its Alzheimer’s disease phase 2b/3 trial has now enrolled 60 participants and expects to reach 100 by the end of this quarter. That milestone will trigger an interim analysis of available trial data by an independent Data Monitoring Committee approximately 6 months later. Final results for the full 220 participants are expected in Q4 2026.
XanaMIA is enrolling 220 participants with biomarker-positive, mild-moderate disease who have elevated levels of the blood biomarker pTau181, designed to identify participants whose disease is likely to progress, and therefore augment the ability to detect a Xanamem treatment benefit. The primary endpoint of the trial is the Clinical Dementia Rating – Sum of Boxes scale, universally included in contemporary AD trials. Other measures include the effects of Xanamem on clinical endpoints of cognition and functional ability.
More than 560 people have been pre-screened with a blood pTau test. Sixty participants have entered the 36-week treatment phase of the trial and another 35 have passed pTau, most of whom are expected to be enrolled in the coming weeks. Patient recruitment and randomization activities are accelerating further with the opening of new US clinical sites, bringing the total number of clinical sites to 35.
Successful FDA meeting on Major Depressive Disorder program
Last year, clinically significant benefits were shown on depressive symptoms in a predominantly co-treated population in the phase 2a XanaCIDD trial with the same 10 mg daily dose being used in the Alzheimer’s disease program. In a positive and collaborative meeting, Actinogen and the FDA reached a common understanding of the additional clinical trials, ancillary clinical pharmacology trials and nonclinical studies required to apply for marketing approval of Xanamem® (emestedastat) for MDD.
A similar Type C meeting for Alzheimer’s disease (AD) will be held with the FDA’s Neurology Division later in 2025 to define the optimal path to a marketing approval.
Dr Steven Gourlay, Actinogen’s CEO and Managing Director, said:
“The accelerating enrolment in the XanaMIA Alzheimer’s disease trial means that further confirmation of the clinical benefits of Xanamem’s brain “cortisol control” mechanism is fast approaching.
“We believe that Xanamem can provide a safe and effective option for patients with mild to moderate Alzheimer’s by slowing disease progression as a once-a-day pill without the expensive monitoring requirements necessary for the approved anti-amyloid antibody drugs.
“We are pleased with the positive and clear outcomes from our Type C meeting with the FDA on major depressive disorder (MDD) that provided excellent guidance for our Xanamem program.”
Upcoming Clinical Trials Science Forum webinar – The critical importance of preparing for commercialization
Actinogen will be conducting another ‘plain English’ Clinical Trials Science Forum webinar on May 14 at 9pm US Eastern (11am May 15 Australian Eastern time).
Chief Medical Officer Dr Dana Hilt will be joined by leading geriatrician Associate Professor Michael Woodward AM MB BS MD FRACP to discuss the scope of leading current and potential treatments in development for Alzheimer’s disease and the ongoing significant unmet medical need for new and effective therapies.
Chief Commercial Officer Andy Udell will outline what commercial planning entails for a company like Actinogen that is in late-stage clinical development.
A recording of the webinar will be made available as soon as possible after the conclusion of the event on the company’s website and YouTube channel.
Actinogen Medical (ACW) is an ASX-listed, biotechnology company developing a novel therapy for neurological and neuropsychiatric diseases associated with dysregulated brain cortisol. There is a strong association between cortisol and detrimental changes in the brain, affecting cognitive function, harm to brain cells and long-term cognitive health.
Cognitive function means how a person understands, remembers and thinks clearly. Cognitive functions include memory, attention, reasoning, awareness and decision-making.
Actinogen is currently developing its lead compound, Xanamem, as a promising new therapy for Alzheimer’s Disease and Depression and hopes to study Fragile X Syndrome and other neurological and psychiatric diseases in the future. Reducing cortisol inside brain cells could have a positive impact in these and many other diseases. The cognitive dysfunction, behavioural abnormalities, and neuropsychological burden associated with these conditions is debilitating for patients, and there is a substantial unmet medical need for new and improved treatments.
Clinical Trials
The XanaMIA Phase 2b/3 Alzheimer’s disease trial is a double-blind, 36-week treatment, placebo-controlled, parallel group design trial in 220 patients with mild to moderate AD and progressive disease, determined by clinical criteria and confirmed by an elevated level of the pTau181 protein biomarker in blood. Patients receive Xanamem 10 mg or placebo, once daily, and its ability to slow progression of Alzheimer’s disease is assessed with a variety of endpoints. The primary endpoint of the trial is the internationally-recognized CDR-SB (Clinical Dementia Rating scale – Sum of Boxes). The trial is being conducted in Australia and the US. Initial results from an interim analysis triggered by the 100th participant reaching 24 weeks of treatment are anticipated in Q4 2025 and final results Q4 2026.
The XanaCIDD Phase 2a depression trial was a double-blind, six-week proof-of-concept, placebo-controlled, parallel group design trial in 167 patients with moderate, treatment-resistant depression and a degree of baseline cognitive impairment. Participants were evenly randomized to receive Xanamem 10 mg once daily or placebo, in most cases in addition to their existing antidepressant therapy, and effects on cognition and depression were assessed. Trial results were reported in August 2024 and showed clinically and statistically significant benefits on depression symptoms with positive effects on the MADRS scale (a validated scale of depression symptom measurement) and the PGI-S (a valid patient reported assessment of depression severity). Cognition improved markedly and to a similar extent in both Xanamem and placebo groups.
About Xanamem (emestedastat)
Xanamem’s novel mechanism of action is to control the level of cortisol in the brain through the inhibition of the cortisol synthesis enzyme, 11β-HSD1, without affecting production of cortisol by the adrenal glands. Xanamem is a first-in-class, once-a-day pill designed to deliver high levels of cortisol control in the brain.
Chronically elevated cortisol is associated with progression in Alzheimer’s Disease and excess cortisol is known to be toxic to brain cells. Cortisol itself is also associated with depressive symptoms and when targeted via other mechanisms has shown some promise in prior clinical trials. The recent XanaCIDD trial demonstrated clinically and sometimes statistically significant benefits on depressive symptoms.
The Company has studied 11β-HSD1 inhibition by Xanamem in approximately 400 volunteers and patients in eight clinical trials. Xanamem has a promising safety profile and has demonstrated clinical activity in patients with depression, patients with biomarker-positive Alzheimer’s disease and cognitively normal volunteers. High levels of target engagement in the brain with doses as low as 5 mg daily have been demonstrated in a human PET imaging study.
Xanamem is an investigational product and is not approved for use outside of a clinical trial by the FDA or by any global regulatory authority. Xanamem® is a trademark of Actinogen Medical.
Disclaimer
This announcement and attachments may contain certain “forward-looking statements” that are not historical facts; are based on subjective estimates, assumptions and qualifications; and relate to circumstances and events that have not taken place and may not take place. Such forward looking statements should be considered “at-risk statements” – not to be relied upon as they are subject to known and unknown risks, uncertainties and other factors (such as significant business, economic and competitive uncertainties / contingencies and regulatory and clinical development risks, future outcomes and uncertainties) that may lead to actual results being materially different from any forward looking statement or the performance expressed or implied by such forward looking statements. You are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. Actinogen Medical does not undertake any obligation to revise such statements to reflect events or any change in circumstances arising after the date hereof, or to reflect the occurrence of or non-occurrence of any future events. Past performance is not a reliable indicator of future performance. Actinogen Medical does not make any guarantee, representation or warranty as to the likelihood of achievement or reasonableness of any forward-looking statements and there can be no assurance or guarantee that any forward-looking statements will be realised.
_______________________ ® Xanamem is a registered trademark of Actinogen Medical Limited
CONTACT: Dr. Steven Gourlay CEO & Managing Director P: +61 2 8964 7401 E. steven.gourlay@actinogen.com.au Investors Michael Roberts Investor Relations M: +61 423 866 231 E. michael.roberts@actinogen.com.au Media George Hazim Media & Public Affairs Australia M: +61 417 516 262 E: georgehazim@mediaaffairs.com.au
