A recent global trial has confirmed that donanemab, an experimental Alzheimer's drug developed by Eli Lilly, can slow the rate of cognitive decline in patients with early-stage Alzheimer's disease. The antibody therapy targets and removes beta-amyloid plaques, a key pathological feature of Alzheimer's, offering a potential new approach to managing the disease. The findings, published in JAMA, suggest that early intervention with donanemab can provide meaningful benefits, allowing patients to retain more of their day-to-day functions for a longer period.
Mechanism of Action and Efficacy
Donanemab works by binding to and clearing abnormal amyloid plaques from the brain. Data from the clinical trial indicate that the drug can rapidly clear nearly 90% of amyloid plaque. This clearance appears to reduce damage to the brain and slow cognitive decline. The trial results showed that, on average, donanemab slowed the progression of the disease by 20-30%, which translates to approximately four to seven months over the 18-month trial period. While not a cure, this modest slowing could allow patients to maintain independence for a longer time before requiring extensive care.
Patient Selection and Treatment Regimen
The trial results indicated that patients in the earliest stages of Alzheimer's, particularly those with low levels of tau protein in their brains, experienced the greatest benefit from donanemab. Amyloid plaques are thought to initiate the disease process, with tau tangles forming later and driving more severe brain damage. Therefore, removing amyloid early, before tau spreads, appears crucial. Donanemab is administered as an intravenous infusion once every four weeks. Regular brain scans are necessary to monitor for potential side effects, such as brain swelling and bleeding, which, while usually resolving on their own, can be fatal in rare cases.
Comparison to Other Therapies
Donanemab functions similarly to lecanemab, another amyloid-targeting antibody therapy developed by Eisai. Lecanemab received accelerated approval from the FDA earlier this year and is currently under review by European and UK regulators. Aducanumab, a third drug approved by the FDA in 2021, has faced concerns regarding cost and effectiveness, limiting its use. While these amyloid-targeting drugs represent a breakthrough, their effects are modest, and many scientists believe that a combination of drugs targeting different aspects of the disease process will ultimately be necessary to halt cognitive decline.
Risks and Side Effects
Treatment with donanemab carries significant side effects, similar to those observed with lecanemab. In the Eli Lilly trial, nearly a quarter of patients experienced some degree of brain swelling or bleeding, compared to only 2% in the control group. Although serious problems were rare, four participants died during the trial – three in the donanemab group and one in the control group. These risks underscore the importance of careful patient monitoring and management.
Future Implications
The emergence of donanemab and other amyloid-targeting therapies marks a turning point in Alzheimer's treatment. While these drugs are not cures, they offer the potential to slow disease progression and improve patients' quality of life. The UK's drugs watchdog, NICE, has already begun assessing donanemab for potential use in the NHS, with the aim of providing recommendations as soon as the drug receives its UK license. The availability of multiple drugs in this class could also promote price competition, making these treatments more accessible to patients in need.
