Alzheon says data backs potential of Alzheimer's candidate

Four years ago, US biotech Alzheon took a gamble on Alzheimer's candidate tramiprosate, thinking it saw potential in the drug despite a failed phase III trial. Now, it has some positive data to back up its view that it could work in a subset of patients with the disease.

Alzheon is developing a prodrug of tramiprosate, an anti-amyloid drug originally developed by Canadian for Bellus Health/Neurochem as Alzhemed but scrapped by its developer in 2009 after showing no activity in trials involving mild-to-moderate Alzheimer's patients. Like dozens of other shelved amyloid-targeting agents, it would have been all-but forgotten had Alzheon not decided to start work on its new version.

The latest results come from delving into the old phase III results for tramiprosate, and suggest the drug could have disease-modifying potential in patient who were homozygous - ie had two copies - of the ApoE4 gene and also had mild Alzheimer's.

The APOE4 allele, present in approximately 10%-15% of people, increases the risk of Alzheimer's and also lowers the age of onset. Having one copy can increase your risk two- to three-fold, while two copies can increase the risk by 12 times.

Prior analyses have suggested tramiprosate may have a much greater effect in ApoE4 homozygotes, who accounted for 13%-15% of the 2,000-plus phase III trial population. The new analysis takes that further by drilling down into that group, and examining the effects of the drug on those in the earlier stages of Alzheimer's.

The subgroup with mild disease at baseline - those with Mini Mental State Examination (MMSE) scores of 22 and higher - showed greater efficacy signals with the drug on both cognition and function than the overall mild-to-moderate group, say the researchers, who have published the research in the Journal of the Prevention of Alzheimer’s Disease.

"The cognitive effect increased significantly with time, suggesting a potential disease-modifying effect of tramiprosate," they conclude. Tramiprosate is thought to work by inhibiting the aggregation of beta amyloid monomers into toxic oligomers.

Alzheon's founder and chief executive Martin Tolar - a biotech industry veteran - said the new results "have 'connected the dots' for directing our anti-amyloid treatment to the patient population most likely to benefit."

Alzheon announced plans for a phase III programme for the ALZ-801 prodrug - which has a longer half-life than its parent and can be dosed once-daily - last year, after reporting phase Ib safety data for the compound at the Alzheimer's Association International Conference (AAIC) in Toronto.

That has still not started, but the company's chief medical officer Susan Abushakra says that it is "poised" to start the pivotal programme for the drug.