Actinogen Reveals Promising Data on Alzheimer’s Therapy at AAIC 2016, Readies Phase 2 Trial

Actinogen Medical announced early clinical study data for Xanamem, a drug designed to lower brain cortisol and intended for the treatment of Alzheimer’s disease, at the Alzheimer’s Association International Conference (AAIC) 2016, held in Toronto, Canada.

Xanamem works by blocking excess cortisol production in the hippocampus and frontal cortex, two brain areas that are particularly affected by Alzheimer’s. The concept is based on findings showing that chronic stress and elevated cortisol levels lead to changes in the brain that affect memory, the development of amyloid plaques, and the death of neurons.

The development of Xanamem is also supported by recent data, presented at the AAIC, demonstrating that increased levels of the stress hormone cortisol in the blood increases the likelihood of developing Alzheimer’s. The findings were part of the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) — an ambitious program with the goal to identify factors, both biological and environmental, that impact the development of Alzheimer’s.

The study, “Plasma cortisol, amyloid-β and cognitive decline in preclinical Alzheimer’s disease,” which enrolled 416 people, also found that cortisol seems to interact with amyloid-beta to speed up cognitive decline, independent of a range of risk factors, including age, education, APOE and BDNF genotype, blood vessel disease, depression, and anxiety.

“We have demonstrated that when levels of cortisol, the ‘stress hormone,’ become chronically elevated in the blood, there is a strong correlation with the subsequent development of Alzheimer’s disease,” Colin L. Masters, MD, professor at the Florey Institute of Neuroscience and Mental Health in Australia, and a co-author on the AIBL study, said in a news release. “This finding, and the results showing synergy with the buildup of beta-amyloid plaques in the brain, suggests a compelling new area of research for the treatment of Alzheimer’s.”

“These study results demonstrate both the importance of understanding the pathological processes in Alzheimer’s and the compelling need for new approaches to treatment,” added Jeffrey Cummings, MD, director of the Cleveland Clinic Lou Ruvo Center for Brain Health and a co-author of the Xanamem study. “To my eyes, AIBL has provided the most important validation to date for controlling excess cortisol production in individuals at risk for developing dementia.”

Researchers from Actinogen Medical and its partner academic institutions presented their findings in a session titled “Xanamem™ a novel 11β–HSD1 inhibitor with potential to provide durable symptomatic and disease modifying benefits in Alzheimer’s disease.” A Phase 1 study of Xanamem showed that the drug is safe and well-tolerated among healthy volunteers, and most importantly, it can cross the human blood-brain barrier to successfully enter the brain.

Actinogen is starting a Phase 2 randomized clinical trial, called XanADu (NCT02727699), that will explore how 12 weeks of Xanamem treatment can impact patients with mild Alzheimer’s disease. The study is planning to begin recruiting 200 people across multiple trial sites in the U.S., Australia, and the U.K. during the second half of 2016. Contact and other information regarding this trial is available through its clinical trials.gov website.

Its main goal will be to improve scores on two Alzheimer’s assessment tools, called the Alzheimer’s Disease Composite and Alzheimer’s Disease Assessment Scale-Cognitive.

“Independent validation is clearly emerging that excess cortisol is a key target for treating the disease and our XanADu trial aims to demonstrate that inhibiting cortisol in the brain with Xanamem is an effective treatment option for patients with mild Alzheimer’s disease,” said Dr. Bill Ketelbey, Actinogen Medical’s CEO.

“We believe this is a promising compound, and we are excited to see the progress into Phase 2 testing,” added study co-author Craig Ritchie, MD, PhD, of the University of Edinburgh.