H. Lundbeck A/S (Lundbeck) and Otsuka Pharmaceutical Co., Ltd. (Otsuka) announced today the continuation of the development program of Lu AE58054 for the treatment of Alzheimer's disease, initiating the first out of four phase III clinical trials with the compound.
The investigational compound Lu AE58054 is a selective 5-HT6 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 III program, which is planned to include four trials. 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 up to 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 improvements 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.
"Following consultations with different health agencies we are now ready, together with Otsuka, to start this major program," said Executive Vice President Anders Gersel Pedersen, Head of Research & Development at Lundbeck, and continued: "There is a strong need for more treatment options for patients with Alzheimer's disease, and we see Lu AE58054 as a potentially promising therapy for this devastating disease."
William H. Carson, M.D., President and Chief Executive Officer, Otsuka Pharmaceutical Development and Commercialization, Inc., said: "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."