Positive Xanamem® Trial Shows Potential Efficacy in Alzheimer's Patients with High pTau

Actinogen Medical Limited has announced the publication of its phase 2a biomarker trial in the 100th edition of the Journal of Alzheimer's Disease. The study, titled "Plasma pTau181 Predicts Clinical Progression In A Phase 2 Randomized Controlled Trial of the 11β-HSD1 Inhibitor Xanamem for Mild Alzheimer's Disease," focuses on the predictive value of plasma pTau181 in Alzheimer's disease (AD) progression. 

The trial included 72 patients from the previous XanADu phase 2a trial, all of whom had stored plasma samples and provided informed consent for the new study. These participants were treated daily with either Xanamem 10 mg or a placebo for 12 weeks. The analysis revealed that patients with elevated pTau181 levels experienced quicker disease progression in key clinical measures such as ADCOMS and CDR-SB compared to those with lower pTau181 levels.

In patients with elevated pTau181, Xanamem showed a potentially significant treatment effect on the CDR-SB scale, indicating a slower disease progression compared to the placebo group. Positive trends were also observed in cognitive tests, aligning with earlier phase 1b studies that demonstrated improved attention and working memory in older healthy volunteers.

Dr. Dana Hilt, Chief Medical Officer of Actinogen Medical, emphasized the uniqueness of Xanamem in targeting the 11β-HSD1 enzyme in the brain, noting its effectiveness and safety at doses of 5 and 10 mg/day. The recent publication supports Xanamem's potential to slow AD progression in patients with high plasma pTau181 and its consistency with prior studies showing cognitive benefits.

The trial was conducted with a double-blind protocol, ensuring that neither the trial personnel nor participants knew the treatment assignments until the final analysis. The patients' plasma samples were analyzed by the Clinical Neurochemistry Laboratory at the University of Gothenburg, which was also blinded to the treatment assignments. The tested biomarkers included pTau181, amyloid beta1-40 and -42, glial fibrillary acidic protein, and neurofilament light.

The placebo group consisted of 34 participants with measurable plasma pTau181 levels. Patients with elevated pTau181 showed more rapid clinical deterioration across several endpoints, reinforcing the importance of pTau181 as a biomarker for AD. This finding is consistent with other emerging data and guidelines that support the use of elevated plasma pTau as a diagnostic tool for AD.

The ongoing XanaMIA phase 2b trial is utilizing elevated plasma pTau181 levels to select patients, aiming to demonstrate Xanamem's treatment effect over a 36-week period. The primary evaluation in the high pTau181 group revealed a significant treatment effect of Xanamem in slowing disease progression, particularly as measured by CDR-SB, an 18-point scale assessing both functional and cognitive abilities.

Actinogen Medical is also exploring Xanamem's potential in treating cognitive impairment and major depressive disorder through its ongoing XanaCIDD trial. This six-week, double-blind trial is assessing the effects of Xanamem on cognition and depression in 167 patients, with results expected in early Q3 2024.

Xanamem's mechanism of action involves inhibiting the 11β-HSD1 enzyme to reduce cortisol production in the brain, which is associated with cognitive decline in AD and other neurological conditions. The drug has shown promise in improving working memory and attention in healthy older adults and in slowing cognitive decline in AD patients.

Actinogen Medical continues to investigate Xanamem across various clinical trials, aiming to confirm its therapeutic potential in multiple neurological and psychiatric diseases. The company remains committed to addressing the unmet medical needs of patients suffering from cognitive dysfunction and other neuropsychiatric conditions.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!