The Alzheimer’s disease drug Kisunla (donanemab) recently received approval from the United Kingdom medicines authority, following the U.S. Food and Drug Administration’s marketing authorization in July 2024. However, Kisunla faces reimbursement challenges in the U.K. after the National Institute for Health and Care Excellence (NICE) declared the drug not cost-effective for taxpayers.
NICE evaluates medical technologies to ensure they provide benefits that justify their price premium over standard care. The cost-effectiveness estimate for Kisunla was found to be five to six times higher than NICE’s typical threshold for reimbursement. The final recommendation on Kisunla will be issued after a consultation period, during which the manufacturer, Eli Lilly, and the NHS will provide additional information to address areas of uncertainty.
Kisunla works by removing beta amyloid plaque from the brain, a protein believed to contribute to Alzheimer’s disease. In a phase 3 trial, the drug was shown to clear both beta amyloid and tau plaque, slowing cognitive and functional decline in participants with early symptomatic Alzheimer’s disease.
Similar to Kisunla, the drug Leqembi (lecanemab) faced reimbursement challenges in the U.K. after its approval, with NICE deeming it not cost-effective for taxpayers. Both drugs target Alzheimer’s disease in early-stage patients but have shown limited cost-effectiveness, posing access challenges in countries with single-payer healthcare systems.
In the U.S., where there is no single payer, Medicare conducted a National Coverage Determination for biologics targeting Alzheimer’s disease, including Aduhelm, Leqembi, and Kisunla. Medicare’s coverage decisions are made independently by payers in the public and commercial sectors. Following FDA approval of Leqembi, CMS announced broader coverage for most Medicare beneficiaries with mild cognitive impairment or mild dementia and confirmed amyloid plaques.
CMS requires beneficiaries taking Leqembi and Kisunla to enroll in a patient registry to collect data on the drugs, a prerequisite for reimbursement. Sales of Leqembi in the U.S. have been below initial expectations, reflecting a lack of consensus among neurologists on recommending beta amyloid-directed monoclonal antibodies to patients.
Debating the Clinical Significance of Drug Treatment for Alzheimer’s Disease
Some experts are questioning the extent to which certain drugs slow cognitive decline in Alzheimer’s patients and whether these effects are truly meaningful for patients. This debate stems from concerns about the overall impact of these medications on patients’ quality of life and long-term outcomes.
Additionally, safety concerns have been raised regarding the use of certain drugs for Alzheimer’s treatment. For example, the FDA initially denied approval of a drug called donanemab due to worries about its long-term safety profile. The agency highlighted a higher rate of treatment discontinuation among patients experiencing adverse events such as amyloid-related imaging abnormalities (ARIA), which can lead to serious complications like brain hemorrhage and swelling.
It’s important to note that the approved indication for these drugs can vary between countries. In the U.K., the labeled indication for one drug is specifically for patients with mild cognitive impairment and mild Alzheimer’s disease-related dementia who have a specific genetic marker. This is a narrower indication compared to the U.S., where the FDA recommends testing patients for a specific genetic marker to assess their risk of developing ARIA before starting treatment.
In response to safety concerns, pharmaceutical companies have been working on modified dosing regimens to reduce the risk of side effects. For example, Eli Lilly recently announced that an adjusted dosing regimen for one of their drugs showed a significant reduction in the risk of brain swelling in clinical trials.
Despite these efforts, some patients still experienced ARIA-related complications during treatment. In clinical trials, about 12% of participants developed edema as a result of treatment, with some cases leading to severe outcomes such as brain bleeding and swelling. The need for better management of these side effects has become evident, especially with reports of deaths possibly linked to the use of these drugs.
In conclusion, the challenges surrounding the safety, effectiveness, and cost-effectiveness of drug treatments for Alzheimer’s disease continue to pose obstacles to widespread adoption. As the debate on the clinical significance of these treatments persists, it is crucial to prioritize patient safety and well-being in the management of this complex condition.
