Actinogen Medical (ASX: ACW) has announced “breakthrough” results from its XanaHES higher dose safety study first initiated last year.
The results reaffirm the foundational hypothesis that reducing cortisol levels can improve cognition with the pivotal factor being dosage.
Moreover, the company announced that its trial results “exceeded expectations” and could result in Xanamem being utilised in the treatment of other cognitive impairments including mood disorders.
Earlier this year, Actinogen published the results of its XanADu trial which confirmed a strong safety profile at 10mg dosage but stopped short of indicating cognitive improvement – a result that Professor Michael Woodward from Austin Health labelled as “disappointing”.
The XanADu trial in mild Alzheimer’s patients showed that Xanamem 10mg daily was safe and altered the cortisol pathway but did not demonstrate an improvement in cognition.
More than 50% of people over the age of 65 have elevated cortisol levels which puts them at greater risk of developing Alzheimer’s disease as well as other cognitive impairments.
However, the results announced today as part of the XanaHES trial “exceed all expectations” with Actinogen Medical chief executive officer Dr Bill Ketelbey calling today as “one of the most important days in the company’s history”.
Speaking via conference call to market analysts, Dr Ketelbey explained that Xanamem’s entire hypothesis has now been validated with the company now intending to push forward with obtaining additional information relating to Xanamem including the use of 5mg, 10mg and 30mg dosages in addition to further pharmacokinetic studies.
“Considering the broad array of medical conditions presenting with cognitive impairment and an associated raised cortisol, these promising results provide many opportunities for the ongoing development of the drug,” said Actinogen Medical clinical advisory board member Professor Jeff Cummings from the Cleveland Clinic in the US.
Actinogen is currently progressing a total of nine different studies into Xanamem including phase 1 target occupancy and homogenate binding studies, pre-clinical toxicology and new indications studies.
According to the company the suite of studies is “fully-funded” as a result of last year’s capital raise wit the biotech company “near to completing all nine studies in the very near future”.
“We’re assimilating the data and considering how best to move forward,” said Dr Ketelbey.
“These are incredibly exciting times for the company. We’ve shown that Xanamem works exactly as it was designed to do so these results are exactly what we’ve been looking for.
“As we gather and analyse more data from XanaHES and the other ongoing studies, we are building a much clearer picture of Xanamem’s pharmacology, potential efficacy, safety, and mechanism of action; all of which will aid substantially in planning the future clinical development and commercialisation strategy for the drug,” he said.
The results demonstrate a “significant improvement” in cognition in trial participants dosed with Xanamem 20mg daily for 12 weeks, compared to a placebo alternative.
The XanaHES trial was primarily designed as a placebo-controlled study to investigate the safety of 20mg Xanamem in healthy elderly subjects, but also included an “exploratory assessment of cognition” to evaluate its cognitive efficacy, using the so-called Cogstate Cognitive Test Battery, an industry-standard to gauge cognitive changes.
The Cogstate Battery evaluated six domains of cognition, with the goal of broadly investigating whether 20mg of Xanamem taken daily could positively influence cognition.
Trial results confirmed that cognitive ability improved in three of the six domains investigated after 12 weeks of treatment.
“This is the first time Xanamem has shown such a clear, statistically significant cognitive improvement in humans,” the company said.
In a statement to the market, Actinogen also declared that these results demonstrate an “encouraging clinical efficacy signal” in cognitive domains that are core to cognitive evaluation across many diseases.
Most importantly, the trial results confirmed the company’s hypothesis that lowering cortisol levels can have a positive impact on brain function among Alzheimer’s patients.
The results, therefore, reinforce the hypothesis underpinning the discovery and development of Xanamem and effectively prove that lowering persistently raised cortisol levels in the brain can positively enhance brain function.
Results from the study also showed that Xanamem, at a dose of 20mg daily, significantly reduced serum cortisol levels in the trial participants over the study period as well exhibiting a good safety profile over the 12 weeks of treatment, with no reports of serious adverse events.
Onwards and outwards
The string of positive outcomes in the trial means Actinogen has validated its leading drug candidate Xanamem and raises the probability of the drug being commercialised globally over the coming years.
It will be a “number of years” before Xanamem is made available to the public although there could potentially be early access for patients on compassionate grounds, assuming Actinogen can successfully complete phase 2 trials indicating direct efficacy among affected patients.
During today’s conference call Dr Ketelbey explained that if Xanamem completes a phase 2 clinical trial and continues on its strong development path that first started 15 years ago, Xanamem could potentially be used as a preventative measure to reduce the risk of cognitive impairment – and even more unorthodox – Xanamem could potentially be offered to healthy people to improve cognition despite a lack of any symptoms or brain-related illness.
Such a move would be “highly unprecedented” and would be very difficult to justify but remains a remote possibility, according to Dr Ketelbey.
“There have been so many past failures with the development of Alzheimer’s drugs, so these promising results offer renewed hope for a treatment breakthrough for this devastating disease,” said Professor Michael Woodward from the Austin Health in Melbourne and one of the leading investigators in the XanADu trial.