On October 23, 2024, Eli Lilly's Kisunla, an anti-amyloid beta (Aβ) monoclonal antibody (mAb), received approval from the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain for treating mild cognitive impairment (MCI) and mild Alzheimer’s disease. However, the National Institute for Health and Care Excellence (NICE) simultaneously announced it would not recommend Kisunla for use within the National Health Service (NHS), citing an unfavorable risk-benefit profile and inadequate cost-effectiveness. This decision mirrors NICE's earlier stance on Eisai/Biogen's Leqembi.
Clinical Trial Data and Efficacy
Kisunla's approval was based on the Phase III TRAILBLAZER-ALZ 2 trial, where patients treated with Kisunla experienced a 35% reduction in cognitive and functional decline over 18 months compared to placebo, as measured by the Integrated Alzheimer’s Disease Rating Scale. In comparison, Leqembi, in its pivotal Phase III Clarity AD trial, demonstrated a 27% reduction in clinical decline over 18 months using the Clinical Dementia Rating-Sum of Boxes. Despite these results, the modest effect size has raised concerns among physicians and regulators about whether the cognitive benefits justify the treatment costs. The annual cost of treatment is approximately $36,000 for Kisunla and $25,000 for Leqembi in the US.
Safety Concerns and Monitoring
A notable side effect of anti-Aβ mAbs is the development of amyloid-related imaging abnormalities (ARIAs), including ARIA-E (vasogenic edema). The TRAILBLAZER-ALZ 2 trial reported an ARIA-E rate of 24.0% for Kisunla, with symptomatic ARIA-E occurring in 6.1% of patients. Leqembi showed a lower ARIA-E rate of 12.5%, with symptomatic ARIA-E at 2.8%. To monitor ARIA risk, MRI scans are required before treatment and during subsequent infusions, adding to the overall cost.
NICE's Ongoing Evaluation
NICE has requested additional evidence regarding the magnitude of the drugs' benefits and overall costs. For Kisunla, the duration of treatment and outcomes after treatment cessation remain unclear. A post-authorization safety study is planned by MHRA to assess long-term effects. Real-world data from the US, where both drugs are approved, will be crucial for further evaluation.
Market Projections
GlobalData forecasts that Leqembi and Kisunla could generate approximately $3.5 billion and $2.0 billion in sales, respectively, by 2030 across the eight major pharmaceutical markets (US, France, Germany, Italy, Spain, UK, Japan, and China).
