5-HT6 receptor antagonists: Lu AE58054 for the treatment of Alzheimer's disease
The investigational compound, Lu AE58054 is a selective 5HT6 receptor antagonist with a different proposed mechanism of action than currently available Alzheimer's medications. Notably, a focus on the 5-HT6 receptor is a different approach from the amyloid and tau hypotheses that have underpinned much of the drug research to date on Alzheimer's disease.
Lundbeck and Otsuka are now initiating the Phase 3 program which is currently planned to consist of four trials. Several doses of Lu AE58054 ranging from 10-60 mg will be used in combination with Donepezil ( Aricept ) in order to explore the effect of the compound in mild-to-moderate Alzheimer's disease as adjunctive therapy to acetylcholinesterase inhibitors ( AChEls ). The key endpoints are Alzheimer's Disease Assessment Scale- Cognitive Subscale ( ADAS-cog ), Activities of Daily Living ( ADL ), and the Clinical Global Impression of Change Scale ( CGIC ).
The program will enroll approximately 3,000 patients worldwide. The first trial will enroll 930 patients in the U.S., Canada and 15 other countries, mainly in Europe, and is expected to last up to three years.
Data from the Phase 2 clinical study were presented at the Alzheimer's Association International Conference ( AAIC ) in July. This study showed that adjunctive therapy with Lu AE58054 ( plus 10 mg/day Donepezil ) at the selected dose resulted in statistically significant improvement in cognitive performance, as measured by the ADAS-cog over a 24-week treatment period versus placebo ( plus 10mg/day Donepezil ).
Secondary endpoints, including measures of global status and activities of daily living, also showed positive trends with the addition of Lu AE58054 compared with patients who only received Donepezil, however the differences were not statistical significant. ( Xagena )
Source: Lundbeck, 2013
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