Australian doctors have cautiously welcomed results from a trial showing that an Alzheimer’s drug slowed down early-stage disease by more than one-third.
Pharmaceutical giant Eli Lilly announced this week that a phase 3 trial into the drug donanemab showed it significantly slowed cognitive and functional decline in people with early symptomatic Alzheimer’s disease.
The trial looked at how the drug altered a measure of cognition and ability to take part in daily activities — the Alzheimer’s Disease Rating Scale (iADRS). It found that for people with early stages of Alzheimer’s there was a 35% slowing of decline.
Almost half (47%) of the participants on donanemab — compared to 29% on placebo — had no clinical progression after one year. They also had 40% less decline in their ability to perform daily activities after 18 months.
While the results have not been peer-reviewed, Lilly is now pushing to get the drug approved in the US and elsewhere.
“Not a cure”
Meanwhile doctors and researchers have been encouraged by the results, while cautioning it is not a cure.
Professor Bruce James Brew, a consultant physician and neurologist at the University of New South Wales, said that while the full results were yet to be published, the data that had been released show it significantly slowed progression of Alzheimer’s.
The drug acted in a similar way to other amyloid monocloncal antibodies and was associated with a similar small risk of cerebral microhaemorrhages and oedema.
“Most impressive was that the drug met all primary and secondary endpoints, meaning that it is likely that patients and carers will notice the effect,” he said.
“It is definitely not a cure for Alzheimer’s, nonetheless, it slows the inevitable worsening of the disease, allowing patients more quality time with loved ones.
“It is hoped that the drug will be available in the not too distant future.”
History of drug failures
Dr Ian Musgrave, a senior lecturer in pharmacology at the University of Adelaide, said that one of the hallmarks of Alzheimer’s disease was the accumulation of a protein called beta-amyloid, which was originally thought to play a critical part in the death of brain cells.
“Nearly a decade of failures with drugs aimed at beta-amyloid have undermined this idea. Most recently, antibodies to beta-amyloid have been trialled to remove the protein. Again, most of these have been abject failures, or produced marginal results at best,” he said.
“In contrast, donanemab is an amyloid plaque-specific antibody, and the recently published clinical trial in participants with early symptomatic Alzheimer’s disease showed clinically significant reductions in disease progression.”
However, despite near total removal of amyloid plaque, the disease still did progress, although at a much slower rate than without treatment.
“While this result is greatly encouraging, it is clear we still have a lot more work to do to successfully treat Alzheimer’s disease,” he said.
More in the pipeline
Professor Colin Masters, Laureate Professor of Dementia Research at the Florey Institute and the University of Melbourne, said it was very exciting news, and the drug looked marginally better than its Eisai competitor.
“We are looking forward to regulatory approval in Australia; and even better-performing biologics in this class are in development,” he said.
Professor Perminder Sachdev, co-director of the Centre for Healthy Brain Ageing, said the results were exciting because it was the third monoclonal antibody in a row to show positive results and the second to show clinical benefits.
“The future for the treatment of Alzheimer’s disease is looking increasingly promising,” he said.
“We need the full data to evaluate it, and the rate of adverse effects is a concern, but I am heartened by the news.”