The quest to develop drugs to treat Alzheimer’s disease has experienced a new setback, with a promising medication failing to show benefits in the latest series of clinical trials.

Earlier trials had suggested that the drug idalopirdine, from the Danish international pharmaceutical company Lundbeck, might improve cognition in those with Alzheimer’s disease when taken alongside existing drugs – known as cholinesterase inhibitors – acting to improve symptoms rather than stopping the disease from developing. But the latest trials have dashed such hopes.

“I was personally very excited,” said professor Clive Ballard, co-author of the study from the University of Exeter, pointing out that previous trials had appeared promising. “It is very disappointing that it then didn’t pan out.”

Writing in the Journal of the American Medical Association, an international team of researchers report how they carried out three clinical trials involving a total of 2,525 participants in 34 countries, to explore the impact of idalopirdine. All participants were aged 50 years or older and had mild to moderate Alzheimer’s disease.

In all trials, participants were randomly assigned to either receive a particular dose of idalopirdine or a placebo alongside their existing Alzheimer’s medication, with neither the patient nor the scientists aware at the time which group each participant was in. All three trials lasted 24 weeks each.

The results were disappointing, revealing that the new drug did nothing to improve cognition or limit the decline of participants, regardless of the dose given. “These findings do not support the use of idalopirdine for the treatment of Alzheimer’s disease,” the authors write.

“I think it is a very big blow,” said Ballard, although he noted that the trials had limitations, not least that participants – including those on placebo – showed little decline over time, suggesting that selection of participants might, at least in part, have masked potential benefits, while the maximum daily doses of idalopirdine given were lower than in previous trials, in part to avoid negative effects on the liver.

What’s more, participants were not required to have tests for biomarkers of Alzheimer’s, such as PET scans or analysis of cerebrospinal fluid, meaning some patients might not have had clumps of amyloid protein in the brain, for example.

Ballard added that to be sure that idalopirdine has no benefits, data from participants at greater risk of decline – such as those who had had scans showing amyloid clumps – should be re-analysed. “I think at the moment [idalopirdine] is almost dead, but there is probably just that one little bit of due diligence to do before it is written off,” he said.

The results come just days after pharmaceutical giant Pfizer announced it was ending research into treatments for Alzheimer’s and Parkinson’s disease, and redirecting funding into other areas.

Dr James Pickett, Head of Research at Alzheimer’s Society, said that the failure of idalopirdine to improve cognition in those with Alzheimer’s was disappointing.



“News from last year showed that a drug that worked in a similar way, intepirdine, also did not have any benefit. These results indicate that this type of drug may not have the effects we were hoping for in people with Alzheimer’s, and we need to broaden our focus,” he said, adding that he remained hopeful that research would uncover new treatments, despite the recent move from Pfizer.

“Advances in technology mean that we are starting to see the hallmarks of Alzheimer’s disease in the living brain and researchers can be confident people enrolled in a trial are definitely affected by Alzheimer’s, rather than something with similar symptoms – which may have been one of the problems facing the idalopirdine trial,” he added. “Such a technological breakthrough will be a vast improvement to the way clinical trials into Alzheimer’s are conducted, and provide great hope for finding a new treatment in the future.”