Breakthrough in Alzheimer's treatment
Apr 23, 2025
Alzheimer's disease, a progressive neurodegenerative disorder, has long posed significant challenges in terms of treatment and management. However, recent advancements in clinical research have brought renewed hope to patients and caregivers alike. One such advancement is donanemab, an investigational antibody therapy developed by Eli Lilly and Company. This blog post delves into the clinical trials of donanemab, highlighting its efficacy, safety profile, and the implications of its approval.
Donanemab is a monoclonal antibody designed to target and remove amyloid plaques from the brain. Amyloid plaques are abnormal clumps of protein that accumulate in the brains of individuals with Alzheimer's disease, contributing to neuronal damage and cognitive decline. By targeting a modified form of beta-amyloid known as N3pG, donanemab aims to slow the progression of the disease investor.lilly.com.
Eli Lilly conducted two pivotal clinical trials to evaluate the safety and efficacy of donanemab:The Guardian+7Neurology live+7Financial Times+7
Initiated in 2017, this trial enrolled 272 participants with early symptomatic Alzheimer's disease. The primary endpoint was the change in the Integrated Alzheimer's Disease Rating Scale (iADRS) score over 76 weeks. Results demonstrated a 32% slowing of cognitive and functional decline in the donanemab group compared to placebo. Additionally, 27% of participants experienced amyloid-related imaging abnormalities (ARIA), a known side effect of amyloid-targeting therapies .ResearchGate+9investor.lilly.com+9Pharmacy Times+9Neurology live+2Pharmacy Times+2investor.lilly.com+2The Guardian+2investor.lilly.com+2Neurology live+2Verywell Health+3Neurology live+3investor.lilly.com+3
Building upon the Phase 2 findings, this larger trial enrolled 1,736 participants across 277 sites in eight countries. The study aimed to confirm the efficacy and safety of donanemab in a broader population. Key findings include:
A 35% reduction in disease progression in patients with low to medium tau levels over 18 months.
A 22% reduction in disease progression in the overall study population.
A 39% lower risk of progressing to the next clinical stage of Alzheimer's disease investor.lilly.com.
These results were published in JAMA and presented at the Alzheimer's Association International Conference.
While donanemab demonstrated significant efficacy, safety concerns were noted:
Amyloid-Related Imaging Abnormalities (ARIA): Observed in 26.8% of treated participants, with 6.1% experiencing symptomatic ARIA.
Infusion-Related Reactions: Reported in 8.7% of participants, most cases were mild to moderate.
Serious Adverse Events: Occurred in 17.4% of the donanemab group, compared to 25.8% in the placebo group Pharmacy Times.
Given these potential risks, careful monitoring through regular brain imaging and clinical assessments is recommended for patients undergoing treatment with donanemab.
In July 2024, the U.S. Food and Drug Administration (FDA) approved donanemab, branded as Kisunla, for the treatment of early symptomatic Alzheimer's disease. This approval was based on the positive outcomes from the TRAILBLAZER-ALZ 2 trial. Kisunla is administered via monthly intravenous infusions, with the cost approximately $12,522 for six months. Medicare and Medicaid may provide coverage, subject to specific monitoring requirements Verywell Health.
The approval of donanemab marks a significant milestone in the treatment of Alzheimer's disease. Unlike previous therapies that primarily addressed symptoms, donanemab represents a disease-modifying treatment that targets the underlying pathology. Its ability to slow cognitive and functional decline offers patients and caregivers renewed hope for maintaining quality of life.
However, the risk of ARIA underscores the importance of early diagnosis and personalized treatment approaches. Ongoing research aims to refine patient selection criteria and optimize treatment regimens to maximize benefits while minimizing risks.
Donanemab's journey from clinical trials to FDA approval exemplifies the progress being made in Alzheimer's disease research. While challenges remain, the advent of disease-modifying therapies like donanemab offers a promising horizon for individuals affected by Alzheimer's disease. Continued research and vigilance in patient management will be crucial in realizing the full potential of this groundbreaking treatment.