Lundbeck, Otsuka Begin Alzheimer’s Trials

H. Lundbeck A/S and Otsuka Pharmaceutical Co., Ltd. have begun the first of four Phase III trials of Lu AE58054 for the treatment of Alzheimer’s disease. Lu AE58054 is a selective 5-HT6 receptor antagonist with a different proposed mechanism of action than currently available Alzheimer’s medications. It focuses on the 5-HT6 receptor, a different approach from the amyloid and tau hypotheses that have underpinned much of the drug research to date on Alzheimer’s disease.

Several doses of Lu AE58054 ranging from 10-60 mg will be used in combination with donepezil in order to explore the effect of Lu AE58054 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. The first trial will enroll 930 patients in the U.S., Canada and 15 other countries mainly in Europe, and is expected to last as long as three years.

Data from the phase II clinical study were presented at the Alzheimer’s Association International Conference (AAIC) in July 2013. This study showed that adjunctive therapy with Lu AE58054 (plus 10 mg/day donepezil) at the selected dose resulted in statistically significant improvement (p=0.004) in cognitive performance, as measured by the ADAS-cog (Alzheimer’s Disease Assessment Scale-cognitive sub-scale) over a 24-week treatment period versus placebo (plus 10 mg/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 statistically significant.