Actinogen Limited announces that the publication of its most recent peer-reviewed article entitled Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease in Clinical Pharmacology in Drug Development, the journal associated with the American College of Clinical Pharmacology.

The review confirms the utility of the 10 mg daily dose of Xanamem® being used in current clinical trials. From a drug development perspective, it demonstrates the value of using central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and endocrine-based PD for determining the target dose range for clinical efficacy testing.

Earlier PK modeling suggested that 20 mg daily would be optimal to maintain cerebrospinal fluid concentrations above the brain half maximal inhibitory concentration. However, subsequent PET scanning suggested that Xanamem doses of 10 mg or even 5 mg daily may be sufficient to adequately inhibit its 11β-HSD1 enzyme target. With once-daily doses of 5-20 mg in cognitively normal, older volunteers, a consistent pattern of pro-cognitive benefit, without dose-response, was seen as improvement in attention and working memory but not episodic memory. Taken in combination, this confirms that the target dose range for Xanamem therapeutic activity is 10 mg daily and not higher.

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 of the first 100 participants are anticipated in Q4 2025 and final results H2 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).

 

Source: prnewswire.com

Report Abuse