Durable benefits previously reported for the MADRS depression scale are supported by the patient-reported outcome of PGI-S and new MADRS responder analyses that underscore benefit at week 10 with a 50% higher rate of remission of depression
SYDNEY, Aug. 26, 2024 /PRNewswire/ -- Actinogen Medical ASX: ACW ("ACW" or "the Company") announces that on-going analysis of the XanaCIDD phase 2a depression trial data found a consistent benefit of Xanamem® treatment on symptoms of depression in a variety of different endpoints. The consistent benefits observed support the conclusion that a 10 mg Xanamem dose is active in controlling brain cortisol and has clinically significant anti-depressant activity.
Highlights of the updated results are:
Management will discuss the depression data and what the trial results reveal about Xanamem's cortisol control mechanism in a webinar at 11am (AEST) on Thursday, August 29 or 9pm (US ET) on Wednesday, August 28. Click here to pre-register or simply register and attend on the day.
Presentation slides for the webinar will be released in an ASX announcement prior to the webinar.
Dr Steven Gourlay, Actinogen's CEO said:
"The data on depression are incredibly good news for Actinogen and for the many patients who may benefit from Xanamem in the future. This trial shows that Xanamem's mechanism of cortisol control in the brain has major clinical impact."
"This trial confirms our conclusion that a 10 mg daily dose of Xanamem is clinically active in the brain and has the potential to be an effective anti-depressant with a novel mechanism. While the anti-depressant market is competitive, Xanamem's safety profile stands it apart from the competitors and the durability of benefit seen is intriguing."
"Anti-depressant activity would also be a beneficial feature of Xanamem treatment for Alzheimer's disease, where depressive symptoms often occur. Our current primary objective remains enrolment of the XanaMIA Phase 2b trial designed to measure Xanamem's ability to slow or halt Alzheimer's disease progression over 36 weeks. Interim data are anticipated in mid 2025."
Details of the additional XanaCIDD trial findings from further exploration of secondary endpoints and subgroups are:
Details of the design of the XanaCIDD phase 2a trial are:
[1] MADRS (The Montgomery-Asberg Depression Rating Scale) is a structured psychiatric interview evaluating MDD symptoms |
[2] Patient Global Impression of (depression) Severity (PGI-S) is a self-assessment of depression severity on a 7-point scale |
[3] Remission of depressive symptoms defined as MADRS < 10 points |
[4] P values are 2-sided, Cd: Cohen's d statistic of effect size – > 0.25 - 0.3 regarded as clinically significant in depression |
About Actinogen Medical
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.
Current Clinical Trials
The XanaCIDD Phase 2a cognition & depression trial is a double-blind, six-week proof-of-concept, placebo-controlled, parallel group design trial in 167 patients. Participants are evenly randomized to receive Xanamem 10 mg once daily or placebo, in some cases in addition to their existing antidepressant therapy, and effects on cognition and depression are assessed. Positive topline results on depression were announced 12 August CY2024.
The XanaMIA Phase 2b 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 effects on cognition, function and progression of Alzheimer's disease are assessed. Thus, Xanamem is being assessed in this trial for its potential effects as a both a cognitive enhancer and a disease course modifier. Initial results from an interim analysis of the first 100 participants are anticipated in mid 2025.
About Xanamem
Xanamem's novel mechanism of action is to block the production of cortisol inside cells through the inhibition of the 11β-HSD1 enzyme in the brain. Xanamem is designed to get into the brain after it is absorbed in the intestines upon swallowing.
Chronically elevated cortisol is associated with cognitive decline in Alzheimer's Disease and excess cortisol is known to be toxic to brain cells. Cognitive impairment is also a feature in Depression and many other diseases. Cortisol itself is also associated with depressive symptoms and when targeted via other mechanisms has shown some promise in prior clinical trials.
The Company has studied 11β-HSD1 inhibition by Xanamem in more than 300 volunteers and patients, so far finding a statistically significant improvement in working memory and attention, compared with placebo, in healthy, older volunteers in two consecutive trials and clinically significant improvements in functional and cognitive ability in patients with biomarker-positive mild AD. Previously, 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. A series of Phase 2 studies in multiple diseases is being conducted to further confirm and characterize Xanamem's therapeutic potential.
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.