#Australia #Sydney #Actinogen Medical #Xanamem #Emestedastat

Actinogen Medical's New Publication on Xanamem

Actinogen Medical Limited, a biotechnology company based in Australia, has recently announced the publication of a peer-reviewed manuscript focusing on its leading compound, Xanamem (emestedastat). This paper, titled Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease, is featured in the Clinical Pharmacology in Drug Development journal, a prestigious platform associated with the American College of Clinical Pharmacology.

This publication is particularly significant as it validates the utility of a 10 mg daily dose of Xanamem in ongoing late-stage clinical trials aimed at treating Alzheimer’s disease and major depressive disorder. The article emphasizes the importance of using central pharmacodynamics (PD) metrics, like positron emission tomography (PET) and cognitive testing, to complement traditional pharmacokinetic (PK) assessments when determining effective dosage ranges.

Key Findings and Insights

Initial PK modeling suggested that a 20 mg daily dosage might be optimal for maintaining necessary cerebrospinal fluid concentrations. However, subsequent PET scans indicated that doses of 10 mg or even as low as 5 mg could effectively inhibit the target enzyme, 11β-HSD1. Not only did trials with older volunteers demonstrate consistent positive cognitive effects at these doses, but improvements were notably observed in attention and working memory, raising confidence in the targeted 10 mg dosage as the upper limit for therapeutic efficacy.

Dr. Dana Hilt, Actinogen's Chief Medical Officer, stated, “The detailed and thorough drug development steps taken by Actinogen to confirm the target dose range of ≤ 10 mg daily demonstrate the value of careful and stepwise clinical pharmacology testing.” She further added, “Paired with the positive effects on depressive symptoms seen in the XanaCIDD phase 2a trial with a 10 mg dose, we have full confidence in the design and 10 mg dose being used in our current XanaMIA phase 2b/3 Alzheimer’s trial.”

About Actinogen Medical

Actinogen Medical is focused on developing innovative therapies for neurological and neuropsychiatric disorders influenced by cortisol imbalance in the brain. The connection between elevated cortisol levels and cognitive decline has profound implications, given cortisol's negative impact on brain health. Xanamem is being explored not just as a treatment for Alzheimer’s and depression but potentially for conditions like Fragile X Syndrome and other neuropsychiatric disorders.

The company is currently conducting the XanaMIA phase 2b/3 clinical trial, which involves 220 patients diagnosed with mild to moderate Alzheimer’s disease. The efficacy of Xanamem in delaying disease progression will be assessed through various clinical endpoints, primarily utilizing the CDR-SB (Clinical Dementia Rating Scale – Sum of Boxes) metric. Initial results from an interim analysis of the first 100 participants are expected in late 2025, with final outcomes projected for the second half of 2026.

The recent XanaCIDD trial demonstrated considerable advancements in alleviating depression symptoms in treatment-resistant patients, showcasing both clinical and statistical significance on recognized assessment scales. Xanamem’s mechanism aims to address high cortisol levels in the brain without disrupting cortisol production in the adrenal glands, making it a unique compound in neurological therapy.

Ultimately, the promising findings underline the need for further exploration into cortisol’s regulation within the central nervous system, with hopes that Xanamem could pave the way for improved treatments in this challenging area of healthcare.

For more detailed insights, the full article can be accessed through the following link to the journal publication.