The latest from Cogstate, leaders in optimizing the measurement of cognition

New Study Links Rilapladib To Cognitive Improvement

September 13, 2015

“The finding that rilapladib improved cognition in this group is very exciting”

In a much anticipated research update, GlaxoSmithKline (GSK) has released the results of a two-year study of rilapladib as a possible treatment for dementia. Using tests for executive function and working memory from Cogstate, GSK researchers were able to observe cognitive improvement in patients with possible mild AD, who also had neuroimaging evidence of cerebrovascular disease, after administration of a daily dose of 250mg of rilapladib.

Rilapladib is an inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) and it was originally developed by GSK to treat atherosclerosis and cardiovascular disorders but has now been shifted to research with Alzheimer’s disease (AD) and associated dementias.

Beginning in October of 2011, 124 adult volunteers, aged 50-80, were enrolled in a Phase 2 clinical trial to compare daily doses of rilapladib to placebos over 24 weeks. The primary end point measurements were on beta amyloid plaque volume in the brain and a composite performance score on working memory and executive function.

The test volunteers completed the cognitive assessments at screening, baseline, week 12 and week 24 and included a Cogstate computerized battery as well as pen and paper neuropsychological tests. A combined score on working memory and executive function was used to measure the effect of rilapladib on cognitive performance.

While no significant change was detected in cerebrospinal fluid [CSF] amyloid beta peptide, there was a noticeable improvement in the cognitive performance endpoint.

“As a whole, the findings provide initial evidence supportive that rilapladib and inhibition of Lp-PLA2 may have the potential to slow the progression of AD and alter the underlying pathology in a subpopulation of AD patients with neuroimaging evidence of CVD,” concluded the researchers.

The GSK researchers were optimistic about the future of rilapladib but called for further study across a larger sample population over a longer time span.

“Although these findings are encouraging, a note of caution is required,” wrote the researchers. “This is the first study to investigate Lp-PLA2 inhibition in AD. Replication of data in AD has been notoriously difficult in recent years particularly for disease-modifying compounds and particularly when moving from small, experimental phase 2 studies to longer term clinical studies.”

“Important next steps to build on the findings here will be to more fully understand the different segments of the dementia population; to further evaluate the cognitive profile over a longer time course and across a wider range of domains; and to assess the impact on other clinically established outcomes such as function and quality of life.”

The research has been published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions.

The combination of test volunteers with early signs of dementia and cerebrovascular disease was unique, adding to the significance of the study results.

“The data in this study is important because it is one of the first studies to focus a priori on the treatment of cognitive dysfunction in individuals with dementia who do not have stroke but who have significant cerebrovascular disease,” said Paul Maruff, PhD, Chief Science Officer at Cogstate. “In most studies of AD, people such as these would be excluded. However outside of clinical trial populations, dementia most likely appears as a combination of both Alzheimer and vascular etiologies. Hence the finding that rilapladib improved cognition in this group is very exciting.”

Questions or comments?  Please contact Dan Peterson