The UK's National Institute for Health and Care Excellence (NICE) has announced that Eli Lilly's Kisunla (donanemab), an Alzheimer's disease drug approved in the UK in October 2024, is not considered cost-effective for reimbursement within the National Health Service (NHS). This decision follows the drug's approval by the UK regulatory authority and the FDA approval in the United States in July 2024.
For NICE to recommend a medical technology for widespread NHS reimbursement, the product must offer benefits to patients that justify its price relative to existing standard care. NICE calculated that Kisunla's cost-effectiveness was five to six times higher than the agency's typical threshold, leading to the current rejection.
Clinical Efficacy and Mechanism of Action
Kisunla works by removing beta amyloid plaque from the brain, a process hypothesized to slow the progression of Alzheimer's disease. In a Phase 3 trial involving approximately 1,700 participants with early symptomatic Alzheimer's disease and amyloid and tau pathology, 47% of those treated with donanemab showed no signs of cognitive decline after one year, compared to 29% in the placebo group.
NICE's Concerns and Future Steps
NICE has requested additional information from Eli Lilly and the NHS to address uncertainties in the available evidence. A final recommendation will be issued after a consultation period concludes later this month, with an independent committee set to review all responses and analyses at a second meeting.
Comparison to Leqembi and US Market Dynamics
A similar situation occurred with Leqembi (lecanemab), which was approved by the British regulatory authority in August but subsequently opposed for reimbursement by NICE. Leqembi, administered as an infusion every two weeks, showed comparable safety and efficacy data to Kisunla, which is administered every four weeks.
In the United States, Medicare has taken the unusual step of issuing a National Coverage Determination (NCD) for biologics targeting Alzheimer's disease, including Aduhelm (aducanumab), Leqembi, and Kisunla. This decision was influenced by Aduhelm's controversial approval, uncertainties regarding safety and efficacy, and the potential cost impact given the large number of eligible beneficiaries. The annual cost of Kisunla in the U.S. is approximately $32,000.
Safety Concerns and APOE ε4 Status
Safety concerns persist, particularly regarding amyloid-related imaging abnormalities (ARIA), which can lead to brain hemorrhage and swelling. The FDA initially raised concerns about donanemab's long-term safety, noting a higher rate of treatment discontinuation due to adverse events. Eli Lilly recently announced that an adjusted dosing regimen in a Phase 3 trial significantly reduced the risk of brain swelling.
The labeled indication in the U.K. is narrower than in the U.S., specifying use in patients with mild cognitive impairment and mild Alzheimer’s disease-related dementia who have only one copy of the apolipoprotein E ε4 allele or do not carry it at all. The FDA recommends testing APOE ε4 status prior to treatment initiation to assess ARIA risk.
