Eli Lilly's own research has confirmed that its breakthrough Alzheimer's medication donanemab, while effective at slowing disease progression, significantly increases the risk of potentially life-threatening brain abnormalities in patients.
The study, examining data from more than 3,000 patients with early Alzheimer's disease across two three-year clinical trials, found that 31% of those receiving donanemab experienced brain bleeds, compared to just 1.9% in the placebo group. Additionally, one in four patients developed brain swelling, with nearly 6% experiencing symptoms including confusion, dizziness, and nausea.
"While ARIA-E events were typically transient and asymptomatic, ARIA can be serious, life threatening, or fatal," wrote lead researchers Dr. John Sims and Dr. Jennifer Zimmer, Eli Lilly's senior medical director and associate vice president, respectively. "Therefore, safety monitoring is necessary with donanemab."
Understanding ARIA Risk
The monthly injectable medication works by stimulating the immune system to remove amyloid protein buildup in the brains of people with early-stage Alzheimer's. However, this mechanism can trigger amyloid-related imaging abnormalities (ARIA), causing inflammation of blood vessels in the brain.
For patients experiencing the most serious ARIA cases, symptoms typically appeared within the first three months of treatment. The study noted that 79 patients had to discontinue the medication due to severe side effects.
Regulatory Status and Availability
Donanemab received approval from the UK's Medicines and Healthcare products Regulatory Agency (MHRA) in October 2023, deeming it safe and effective for people in early stages of Alzheimer's disease. However, the National Health Service's cost-effectiveness watchdog, NICE, declined to recommend it for NHS coverage, stating the benefits were "too small" to justify the expense.
The medication is currently available through private clinics in the UK, with London's Re:Cognition Health offering the treatment at approximately £60,000 per year. The first private doses were administered in January 2024.
Clinical Significance
Professor Tom Dening, Professor of Dementia Research at the University of Nottingham, commented on the findings: "I can't see how the cost of the drug, the cost of administering it, and the cost of monitoring can ever be recouped by reduced health service demand. I think NICE has made the right decision."
Despite these concerns, donanemab represents a significant advancement in Alzheimer's treatment. It has demonstrated the ability to slow the progression of the disease by approximately 35% in early stages—more effective than previous treatments. It is only the second drug, after lecanemab, proven to slow Alzheimer's progression.
Alzheimer's Disease Burden
Alzheimer's disease affects approximately 700,000 people in the UK, with dementia costing the country an estimated £42 billion annually. These costs are projected to rise to £90 billion within the next 15 years as the population ages.
The Alzheimer's Society estimates that around one million people in the UK currently live with dementia, with projections suggesting an increase to 1.4 million by 2040. Alzheimer's accounts for approximately 60% of dementia cases.
Dr. Richard Oakley, Associate Director of Research and Innovation at Alzheimer's Society, emphasized: "Donanemab is one of a number of disease-modifying therapies offering a new horizon of hope in the fight against dementia. But as with any new treatment, it's crucial we understand the associated risks to ensure it is effective and safe."
He added, "New treatments are an important catalyst for change but are just one piece of the puzzle."
Balancing Benefits and Risks
The study highlights the complex risk-benefit analysis facing patients, clinicians, and healthcare systems. While donanemab offers meaningful disease-modifying potential, the significant incidence of ARIA and its potentially serious consequences demands careful consideration.
For patients and families affected by Alzheimer's, these emerging treatments represent both new hope and difficult decisions. The high cost of private treatment, combined with safety concerns, means access remains limited despite regulatory approval.
Healthcare systems worldwide continue to grapple with how to evaluate, implement, and potentially fund these new Alzheimer's therapies that offer modest benefits but come with substantial costs and safety monitoring requirements.
