A major clinical trial of an Alzheimer’s drug has confirmed that the therapy can slow the rate at which patients deteriorate, raising hopes that medicine may one day halt the most common form of dementia. What impact could the new drug have?
What is the new drug?
Donanemab is an antibody therapy from the US pharmaceutical giant Eli Lilly. It targets abnormal clumps of a protein called beta-amyloid that can build up in the brain. The plaques are considered one of the pathological hallmarks of Alzheimer’s disease. The drug works by binding to the abnormal amyloid and removing it from the brain.
How does it help patients?
The drug works rapidly and can clear nearly 90% of amyloid plaque from the brain, according to data from a clinical trial released on Monday. Removing the toxic protein early enough seems to reduce the damage caused to the brain and slow the rate of cognitive decline.
How effective is the drug?
Donanemab is not a cure. Patients on the drug did not improve, and the treatment did not halt their decline, but they deteriorated more slowly than a control group that received a placebo. After decades of failed trials – and billions of dollars invested in research – proof that drugs can alter the course of the disease is regarded as a significant triumph. On average, the drug slowed the progression of the disease by 20-30%, amounting to about four to seven months over the course of the 18-month trial. Though modest, this could mean patients have more time to live independently before requiring care.
How is the drug given?
Donanemab is administered as an intravenous infusion once every four weeks. Patients need to have regular brain scans to monitor for potential side-effects, including brain swelling and bleeding. These mostly resolve on their own but in rare cases can be fatal.
Who is most likely to benefit?
Those who benefited most from the drug were in the earliest stages of disease and notably had low levels of another toxic protein called tau in their brains. Amyloid protein builds up between brain cells, but when the plaque reaches a certain level it seems to aid the formation of tau tangles inside neurons, driving more severe brain damage. The trial results suggest it is important to remove amyloid before tau spreads.
Are there similar drugs out there?
Yes. Donanemab works in the same way as lecanemab, an amyloid-targeting antibody therapy from Eisai, a Japanese pharmaceutical company. Earlier this year, the US Food and Drug Administration (FDA) gave accelerated approval to lecanemab. European and UK regulators are still reviewing the drug. A third drug called aducanumab was approved by the FDA in 2021, but concerns over cost and effectiveness mean it is rarely used.
Will the drugs cure dementia?
No. These amyloid-targeting drugs are the first generation of therapies that directly affect the progression of Alzheimer’s. And while that is a breakthrough, the effects are modest. Many scientists believe that patients will need a cocktail of drugs to halt cognitive decline, with each working on a different part of the disease process.
What are the risks?
There are significant side-effects with donanemab and they are similar to those seen with lecanemab. In the Eli Lilly trial, nearly a quarter of patients treated experienced some level of brain swelling or bleeding, compared with only 2% in the control group, though serious problems were rare. Four people died while taking part in the trial – three in the donanemab group and one in the control group.
