Lundbeck, Otsuka tout improved cognition in mid-stage Alzheimer's study

Lundbeck and Otsuka Pharmaceuticals are quickly ramping up a 3,000-patient Phase III study for an experimental Alzheimer's drug after claiming success in improving cognition among a group of patients taking the treatment alongside donepezil for 24 weeks in a Phase II trial.

Investigators say they tracked a clear, statistically significant improvement in the combo arm of the Phase II study, which compared results for Lu AE58054/donepezil with a control provided donepezil and a placebo. The primary endpoint was ADAS-Cog at Week 24--which measures the severity of the most important symptoms. But the drug failed to distinguish itself for secondary endpoints on two other measures, though the companies say the trial was not designed to demonstrate statistically significant improvements on either of those measures.

Lu AE58054 is a selective 5-HT6 receptor antagonist, playing on a G-protein coupled receptor found almost exclusively in the brain which plays a role in cognition, among other things. Blocking it can stimulate the release of dopamine and norepinephrine in the frontal cortex, offering a new approach to treating the memory-destroying disease. The companies say they can have a Phase III trial up and running before the end of the year.

The data was presented during the Alzheimer's Association International Conference 2013 in Boston.

Alzheimer's has been a notoriously difficult disease to treat. More than 100 clinical trials have ended in failure, including two big studies for solanezumab and bapineuzumab, two antibodies designed to clear the brain of the toxic amyloid beta protein. But a number of Big Pharma companies have been pressing ahead with new approaches, willing to take on huge risks in anticipation of a megablockbuster market for any drug that can survive the clinical trial gauntlet.

"Lu AE58054 potentially represents a new approach to Alzheimer's disease and a continuation of Lundbeck's commitment to addressing this complicated disease", says Executive Vice President Anders Gersel Pedersen, the head of Lundbeck's R&D division. "It is my hope that the clinical phase III program will confirm results seen from this phase II trial, and demonstrate a positive outcome on this devastating disease.

- here's the press release