The National Institute for Health and Care Excellence (NICE) has issued a preliminary rejection of Eli Lilly's donanemab (Kisunla) for treating mild cognitive impairment and mild Alzheimer's disease within the National Health Service (NHS). This decision follows the drug's approval by the Medicines and Healthcare products Regulatory Agency (MHRA), and mirrors NICE's earlier decision regarding Eisai/Biogen's lecanemab (Leqembi). Both drugs, anti-amyloid beta (Aβ) monoclonal antibodies, represent a new class of disease-modifying therapies (DMTs) for Alzheimer's, but their cost-effectiveness and safety profiles remain under scrutiny.
Concerns over Cost and Clinical Benefit
NICE's decision reflects concerns about the cost-effectiveness of donanemab and the magnitude of its clinical benefits. While donanemab has demonstrated efficacy in reducing amyloid plaques in the brain, uncertainty persists among physicians regarding whether the observed reduction in clinical decline translates to a noticeable difference in cognition for patients. Philippa Salter, Managing Neurology Analyst at GlobalData, noted that the decision was "not unexpected," highlighting the ongoing debate about the real-world impact of these DMTs.
Safety Considerations: ARIA and Monitoring Costs
A significant concern associated with anti-Aβ monoclonal antibodies is the development of amyloid-related imaging abnormalities (ARIAs), which can include brain swelling or microhemorrhages. Monitoring for ARIA necessitates magnetic resonance imaging (MRI) scans before treatment and periodically during infusions, adding to the overall cost of therapy. These safety concerns and associated monitoring costs contribute to NICE's reservations about the cost-benefit ratio of donanemab.
Opportunity for Reconsideration
NICE has requested further evidence regarding the magnitude and duration of the drug's effects, as well as a more comprehensive analysis of its overall costs. Donanemab's treatment regimen differs from lecanemab's in that it is not intended for indefinite use, potentially making its lifetime cost more competitive. Furthermore, the MHRA is planning a post-authorization safety study to evaluate the long-term effects of these drugs, which could provide valuable data for NICE's reconsideration.
The Path Forward: Real-World Evidence and Clinical Trial Data
Real-world evidence from the United States, where both lecanemab and donanemab have been approved and are being prescribed, will be crucial in demonstrating the drugs' effectiveness and safety in a broader patient population. Additional clinical trial data will also be essential in addressing NICE's concerns and potentially paving the way for NHS coverage of these novel Alzheimer's therapies. GlobalData forecasts peak sales in 2030 for Leqembi and Kisunla of approximately $3.5 billion and $2.0 billion, respectively, in the 8MM (US, France, Germany, Italy, Spain, UK, Japan, and China), highlighting the significant market potential contingent on regulatory and reimbursement approvals.
