H. Lundbeck and Otsuka Pharmaceutical Co. have presented the first clinical data on the investigational drug Lu AE58054 in Alzheimer’s disease at the Alzheimer’s Association International Conference 2013 (AAIC 2013) in Boston.

The phase II clinical study demonstrated that treatment with Lu AE58054 as add-on to donepezil for six months improved cognitive performance in patients with moderate Alzheimer’s disease.

“I am very pleased with the data achieved in this project. 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, head of Research & Development at Lundbeck. “It is my hope that the clinical phase III programme will confirm results seen from this phase II trial, and demonstrate a positive outcome on this devastating disease.”

William H Carson, MD, president and chief executive officer, Otsuka Pharmaceutical Development and Commercialisation, Inc., notes that, “Our investigation of the 5-HT6 receptor and its role in memory processes and in Alzheimer’s disease is encouraging. We are eager to continue phase III trials with Lundbeck.”

This phase II clinical study exploring the efficacy and safety of Lu AE58054 as add-on to donepezil was a multi-centre, randomized, double-blind, parallel-group, placebo-controlled trial for a period of 24 weeks. The study was conducted in 278 patients with moderate Alzheimer’s disease in Europe, Canada and Australia.

Lu AE58054 plus donepezil demonstrated significant improvements in cognitive function in Alzheimer's disease compared to placebo plus donepezil:

A Clinical Phase II Study of Lu AE58054 Added to Stable Donepezil Treatment in Patients with Moderate Alzheimer’s Disease (AAIC 2013 oral presentation):

Addition of Lu AE58054 (90 mg/day) to stable donepezil treatment resulted in improved cognitive performance as measured by the primary endpoint ADAS-Cog at Week 24 (p=0.004). The mean difference in ADAS-Cog at Week 24 was -2.16 (95% confidence interval of -3.62 to -0.69). The effect was apparent after 12 weeks.

Secondary efficacy assessments including ADCS-CGIC and ADCS-ADL23 showed a trend in favour of Lu AE58054 treatment at Week 24 compared with patients who only received donepezil, but the differences were not statistically different. The study was not designed to show statistically significant differences for these secondary endpoints.

Treatment with Lu AE58054 was generally well tolerated. Liver enzyme (ALT, AST, GGT) elevations were observed in some patients. Changes in transaminases were asymptomatic and returned towards baseline values in patients who either continued treatment or withdrew from the study.

The presentation will also be published in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.

In the second half of 2013, the phase III clinical programme is expected to commence. The programme is currently planned to enroll approximately 3,000 patients with Alzheimer’s disease. Several doses of Lu AE58054 will be used in combination with donepezil in order to explore in mild-to-moderate dementia of the Alzheimer’s type as adjunctive therapy to acetylcholinesterase inhibitors (AChEls). The programme will enroll patients globally and is expected to last up to three years.

The 5-HT6-receptor is expressed in brain regions involved in cognition, such as the cortex and the hippocampus, and modulates activity of multiple neurotransmitter systems. Lu AE58054 is a selective 5-HT6-receptor antagonist. In pre-clinical models, Lu AE58054 was shown to improve cognition and enhance the effects of the acetylcholinesterase inhibitor donepezil on hippocampal function. A number of early trials have demonstrated that a 5-HT6-receptor antagonist could offer potential benefits in the treatment of disorders such as Alzheimer's disease and in November 2009 Lundbeck initiated the above described 24 week clinical phase II trial with Lu AE58054 as adjunctive therapy in Alzheimer's disease.

Alzheimer's disease is a progressive brain disorder in which the brain gradually degenerates. People with Alzheimer's disease develop distressing changes in memory, thought, function and behavior, which worsen over time. These changes increasingly impact the person's daily life and reduce their independence until ultimately these patients are entirely dependent on others.

Alzheimer's disease is associated with brain shrinkage and disruptions in the activity of neurotransmitters. The largest development efforts to date on investigational drugs for Alzheimer’s have focused on reducing amyloid plaque formation or excessive phosphorylation of tau proteins. The blocking of 5HT6 receptors represents an alternative, potentially promising approach.

Alzheimer's disease also has an enormous impact on the patient's caregiver. Most caregivers are close relatives who provide care at home — a demanding and exhausting role that represents a significant emotional and physical burden.

Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: 'Otsuka-people creating new products for better health worldwide.' Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.

Lundbeck is a global pharmaceutical company highly committed to improving the quality of life of people living with brain diseases.