Lundbeck and its partners at Otsuka are embarking on a lengthy Phase III journey in search of solid evidence that their Alzheimer's drug Lu AE58054 in combination with donepezil can improve the swiftly eroding cognitive functions of Alzheimer's patients. Investigators are launching the first of four Phase III studies of the drug, a 5-HT6 receptor antagonist, with plans to ultimately enroll about 3,000 patients over a period of three years.
The drug plays 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.
A few months ago investigators said 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 arm that was provided donepezil and a placebo. The primary endpoint was ADAS-Cog at Week 24, which measures the severity of the most important symptoms. 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.
By staying focused on cognitive functions, the companies will steer far clear of the amyloid beta and tau hypotheses that dominate much of the research now underway at companies like Eli Lilly ($LLY). Time and again, though, attempts to slow or stop the effects of the disease by clearing toxic proteins has failed, or proved dangerous to patients. So far, the few therapies that are available for the disease do little to help patients, leaving an enormous void that Big Pharma has tried to capitalize on.
"Use of the serotonin 5-HT6 antagonism mechanism against the cognitive effects of Alzheimer's is a promising hypothesis that we will seek to validate more fully in these phase III trials," says William Carson, the CEO of Otsuka Pharmaceutical Development and Commercialization.
- here's the press release