Depression is a widely experienced mental disorder, with around 5% of adults suffering from major depressive disorder (MDD), which often leads to unclear thinking. Recent clinical trials suggest that a new oral medication, taken daily, could offer significant improvements. The drug, Xanamem®, shows potential to help patients who find that antidepressant medications alone do not fully address their symptoms.

Actinogen Medical Limited (ASX: ACW) has successfully administered treatment to the first participant in the XanaCIDD Phase 2 clinical trial for depression. This study is randomised and evaluates the impact of Xanamem on safety, cognitive performance, and depression symptoms in patients whose conditions have not been adequately managed by their current antidepressant medications. These patients also experience cognitive impairments. The drug's safety has been previously established in over 300 patients, indicating that the trials are conducted with large, controlled sample groups that enhance the reliability of the findings, despite the potential neurological effects of the drug. Currently, the Phase 2 trials are over 80% enrolled, which helps strengthen the credibility of earlier results.

What is Important About the Xanamem Phase 2a Clinical Trials?

• It will seek to test whether the drug controls brain cortisol levels 

• It will attempt to improve symptoms of depression

• Phase 2a trial enrolment surpasses 80% 

• Full enrolment is expected in April 2024

• Topline results now expected Q3 CY2024

The six-week Xana CIDD Phase 2 Depression trial is a proof-of-concept study with a parallel-group design, involving around 160 patients. These patients suffer from persistent major depressive disorder (MDD) and cognitive impairments despite receiving standard antidepressant therapy. Participants will be randomly assigned to receive either a 10 mg daily dose of Xanamem or a placebo, in addition to their existing antidepressant regimen. The study aims to assess the effects on cognitive functions using the Cogstate Cognitive Test Battery and measure changes in depression levels with the Asberg Depression Rating Scale. 

Who is Actinogen Medical and What Do They Do?

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 on these and many other diseases. The cognitive dysfunction, behavioural abnormalities, and neuropsychological burden associated with these conditions are debilitating for patients, and there is a substantial unmet medical need for new and improved treatments.

How Does Xanamem Differ from Other Depression Treatments?

Xanamem adopts a unique approach to treating depression by targeting the 11β-HSD1 enzyme in the brain, which is involved in cortisol production. Unlike typical antidepressants, Xanamem is designed to cross the blood-brain barrier after being absorbed in the intestines. High cortisol levels, often linked with cognitive decline in Alzheimer's Disease, are reduced by Xanamem, which has demonstrated improvements in cognition in healthy, older adults.

Over 300 volunteers and patients have been involved in trials studying 11β-HSD1 inhibition by Xanamem, revealing statistically significant enhancements in working memory and attention compared to a placebo in healthy, older adults across two consecutive trials. It also showed clinically significant cognitive improvements in patients with mild Alzheimer’s Disease who are biomarker-positive. These statistically significant results affirm the drug’s efficacy and potential applicability to a broader demographic.

Further research is underway to explore Xanamem’s effectiveness against other conditions and to assess its overall therapeutic potential. Currently, Xanamem remains an investigational drug and has not been approved for use outside of clinical trials by the FDA or any other global regulatory authority.

Depression is notoriously challenging to treat, but Xanamem emerges as a promising solution with substantial potential to alleviate depressive symptoms. This drug focuses on reducing cognitive impairment, a frequent companion of depression and other diseases, by targeting cortisol production. Excess cortisol is commonly linked to depression. Xanamem’s approach involves the modulation of cortisol levels which have shown promise in previous clinical trials when targeted through various mechanisms. The effectiveness of Xanamem in addressing these biochemical pathways positions Actinogen Medical Limited (ASX: ACW) as a notable entity in the pharmaceutical industry and a stock worth watching.