The U.S. Food and Drug Administration (FDA) has granted approval to donanemab, manufactured by Eli Lilly, for the treatment of early symptomatic Alzheimer's disease. This decision marks a significant milestone as donanemab becomes the second drug approved to address the underlying pathology of Alzheimer's, rather than merely managing its symptoms.
Clinical Efficacy and Trial Results
Donanemab, to be marketed under the brand name Kisunla, demonstrated a substantial impact on disease progression in clinical trials. According to Eli Lilly, Kisunla slowed cognitive and functional decline by up to 35% over 18 months when compared to patients receiving a placebo. Furthermore, it reduced the risk of progressing to the next clinical stage of Alzheimer's by up to 39%. These findings suggest that earlier intervention with donanemab can significantly extend the period during which patients maintain independence and cognitive function.
Anne White, executive vice president of Eli Lilly, emphasized the importance of early treatment, stating, "We know these medicines have the greatest potential benefit when people are treated earlier in their disease, and we are working hard in partnership with others to improve detection and diagnosis."
Mechanism of Action
Kisunla is administered via intravenous infusion every four weeks. It functions as a monoclonal antibody, specifically targeting amyloid plaques in the brain, a hallmark of Alzheimer's disease. By binding to these plaques, donanemab facilitates their removal by the body's immune system, thereby slowing the neurodegenerative process.
Safety and Adverse Events
While the clinical trials demonstrated significant benefits, donanemab is associated with potential side effects, including brain swelling or bleeding, referred to as Amyloid-Related Imaging Abnormalities (ARIA). Although most ARIA cases reported during the trials were mild, the FDA noted that the benefits of donanemab outweigh these risks. Monitoring via MRI scans is recommended to detect and manage ARIA effectively. Notably, there were a few deaths (2% in the donanemab arm vs 1.7% in the placebo arm) associated with ARIA during the clinical trials.
Cost and Access
Eli Lilly has priced Kisunla at approximately $695 per vial, translating to about $32,000 for a year's course of treatment. The Centers for Medicare and Medicaid Services (CMS) have indicated plans to cover FDA-approved Alzheimer's drugs, contingent upon physicians maintaining detailed records of patient outcomes. The potential to discontinue treatment after amyloid plaque clearance, as suggested by trial data, could help mitigate long-term costs.
Expert Commentary
Dr. Howard Fillit, co-founder and chief science officer at the Alzheimer’s Drug Discovery Foundation, commented on the approval, stating, "This approval marks another step forward in evolving the standard of care for people living with Alzheimer’s disease that will ultimately include an arsenal of novel treatments, providing much needed hope to the Alzheimer’s community."
Broader Implications
The approval of donanemab arrives at a critical time, with the number of Americans living with Alzheimer's projected to reach nearly 14 million by 2060. The Alzheimer's Association has lauded the approval as a significant advancement, offering patients more options and greater opportunities to extend their independence. This progress is particularly vital given that Alzheimer's and other dementias affect millions of family members and unpaid caregivers, who provided an estimated 18 billion hours of care in 2022 alone.
