The FDA has granted traditional approval to Kisunla (donanemab-azbt) for the treatment of early-stage Alzheimer's disease. This approval marks a significant step forward, offering a new therapeutic option that targets the underlying pathology of the disease.
Targeting Amyloid Plaques
Kisunla is an amyloid-directed antibody designed to target and remove amyloid plaques, a hallmark of Alzheimer's disease. These plaques, formed by the accumulation of aggregated amyloid-beta peptides, are believed to contribute to neurotoxicity and cognitive decline. Kisunla works by enhancing the body's immune system to clear these plaques.
The approval was based on Phase III data from the TRAILBLAZER-ALZ 2 trial, conducted by Eli Lilly and Company. The trial involved 2736 participants across eight countries, all with early symptomatic Alzheimer's disease. Results demonstrated statistically significant improvement in cognitive and functional assessments compared to the placebo group over 76 weeks. These assessments included the Integrated Alzheimer’s Disease Rating Scale (iADRS), the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog13), and the Alzheimer’s Disease Cooperative Study – Instrumental Activities of Daily Living (ADCS-iADL) scale.
Clinical Trial Outcomes
A notable outcome of the trial was the potential for patients to discontinue treatment once amyloid plaques were reduced to undetectable levels. Approximately 47% of patients reached this milestone at the one-year follow-up, and 69% at the 1.5-year follow-up, potentially reducing long-term treatment costs and exposure to the medication.
Safety and Monitoring
Despite its efficacy, Kisunla carries safety risks, including Amyloid-Related Imaging Abnormalities (ARIA), such as temporary brain swelling. In some instances, ARIA can be severe or even fatal. Patients with the ApoE ε4 gene are more susceptible to developing ARIA. The FDA mandates pre-treatment MRI scans and consistent monitoring during therapy to detect ARIA. Warning signs include headaches, dizziness, nausea, confusion, and blurred vision.
Cost and Access
The cost of Kisunla treatment is a significant consideration. The estimated cost for six months of treatment is approximately $12,522, with each vial costing around $696. Medicare may offer sponsorship for Kisunla and diagnostic tests to determine patient eligibility. Eli Lilly & Co. provides a support program for those seeking access to the drug.
Implications for Alzheimer's Management
The approval of Kisunla represents a shift in Alzheimer's disease management, offering a treatment that can potentially slow disease progression and allow patients to discontinue therapy based on biomarker improvement. Anne White, Executive Vice President at Eli Lilly, emphasized the importance of early-stage treatment. Kisunla is also under further investigation in the TRAILBLAZER-ALZ 3 study, which aims to mitigate the development of symptomatic Alzheimer’s in patients with early biomarker indicators of the disease.
