New drug candidate on trial for early-stage Alzheimer's

Australian biotech company Actinogen Medical (ASX: ACW) is progressing a phase I trial on its lead drug candidate, Xanamem, which holds promise as a much-needed new treatment option for people with early-stage Alzheimer’s disease.

The phase I study is being conducted in three parts - the first part assessed safety and tolerability in single ascending doses and the second part, which recently began at the Queen Elizabeth II Medical Centre in Perth, will assess the safety profile of multiple ascending doses in 24 healthy volunteers.

“The first cohort of eight participants was dosed this week,” said Dr Bill Ketelbey, CEO and managing director of Actinogen Medical. “Xanamem will then be taken into a phase II efficacy trial next year which will be conducted in various countries, including Australia - we would like it to include the US, UK and Europe.”

Ketelbey is well placed to oversee the development of a new treatment for Alzheimer’s disease - before taking up the position of CEO and managing director with Actinogen Medical in December 2014 he worked with pharmaceutical giant Pfizer for 19 years where he was involved in the development of Aricept, an acetylcholinesterase inhibitor and market-leading treatment for Alzheimer’s disease globally.

“Alzheimer’s is a compelling area for R&D; there is clearly a market and the area is in desperate need of new and alternative therapies,” said Ketelbey. “There have been no new treatments developed for Alzheimer’s disease for well over 10 years, despite the hundreds of millions of dollars spent on it.”

Although there are four drugs on the market, they have limited benefit and only treat some of the symptoms of Alzheimer’s disease. And Alzheimer’s disease is expected to increase with the ageing population.

Xanamem represents a new approach to treating Alzheimer’s and has the potential to alter the course of the disease by targeting the early symptomatic stage known as mild cognitive impairment.

“Mild cognitive impairment has now been recognised as a precursor to Alzheimer’s disease,” said Ketelbey. “This is an important new development because now we can research and treat the disease further upstream.

“The very scarred brains of patients with moderate to severe Alzheimer’s tend to be very resistant to therapy. We expect we will achieve a better and more meaningful response in patients if we can treat them earlier in the disease course.”

Xanamem acts by blocking hydroxysteroid dehydrogenase 1 (HSD1), the enzyme that catalyses the production of cortisol from cortisone. HSD1 acts intracellularly and is expressed in the hippocampus and frontal cortex - the areas of the brain most affected by Alzheimer’s disease.

“The theory about cortisol was developed at The University of Edinburgh about 10 years ago,” Ketelbey said. “We now know one of the hallmarks of Alzheimer’s is chronic elevated cortisol levels and this has been associated with amyloid deposition, neural death and shrinkage of the hippocampus and frontal cortex. The research, funded by the Wellcome Trust, has been ongoing to identify an adequate cortisol inhibitor.”

Late last year, Actinogen acquired the research from The University of Edinburgh with the remit to advance its development in humans.

“By blocking the HSD1 enzyme, Xanamem does not inhibit the total production of cortisol,” explained Ketelbey. “The pathological premise behind Xanamem is that it dampens down excessive production of cortisol in the brain, which has been identified as the pathological profile of Alzheimer’s in animals and humans.”

Thus, by preventing the overexpression of cortisol, Xanamem will ideally minimise the development of Alzheimer’s.

“The great thing about working in this area is that it is very well coordinated globally,” Ketelbey enthused. “There is a lot of collaboration at the national and international level and patients who are keen to participate can readily be recruited to trials.”

The final Phase 1 study results are expected in mid-2015 and a Phase II efficacy study is planned for early 2016.

Image credit: ©Stockvault/Homero Chapa