NEW YORK – Even though Biogen and Eisai have garnered authorization to market their anti-amyloid Alzheimer's drug Leqembi (lecanemab) in Great Britain, the National Health Service in England may not pay for the treatment if doubts about its cost-effectiveness aren't resolved.
The UK's Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorization to Leqembi for treating mild cognitive impairment and mild dementia due to Alzheimer's disease in adult patients who are ApoE ε4 heterozygotes or non-carriers. The regulatory body made its decision based on data from the Phase III CLARITY AD trial, in which Leqembi-treated patients on average scored 0.45 points better than those on placebo on the 18-point Clinical Dementia Rating-Sum of Boxes scale after 18 months. This translated to a 27 percent slower rate of cognitive decline in the Leqembi arm than in the placebo arm.
However, in a draft guidance on Thursday, the National Institute for Health and Care Excellence (NICE) found Leqembi's benefits lacking and said the treatment wouldn't be a good use of the NHS's limited funds. An independent NICE committee noted that, based on the available data, cognitive functions for patients on Leqembi continued to worsen but at a slower rate than those on placebo. In a statement, NICE Chief Executive Samantha Roberts further characterized Leqembi as "an intensive treatment" that requires patients go to a hospital every two weeks and receive the therapy from skilled medical staff who must monitor them for serious side effects such as amyloid-related imaging abnormalities (ARIA), which can cause swelling and bleeding in the brain.
NICE's independent committee also noted the lack of evidence on the drug's long-term effects since patients were followed for 18 months in the CLARITY AD trial and uncertainties around the sponsors' cost-effectiveness analysis. For example, according to NICE's draft opinion, the sponsors' cost-effectiveness modeling assumed each Leqembi infusion would cost £208 ($272.48), but NICE's independent committee determined that £565 was a more "suitable" estimate, based on the need for "more intensive monitoring and nursing time than chemotherapy."
"For NICE to be able to approve a medicine for use in the NHS, it must not only provide benefits to patients, but it must also represent a good use of NHS resources and taxpayers' money," Helen Knight, NICE's director of medicines evaluation, said in a statement. "Lecanemab provides on average four to six months slowing in the rate of progression from mild to moderate Alzheimer's disease, but this is just not enough benefit to justify the additional cost to the NHS."
In the US, where regulators approved Leqembi based on the same data from the CLARITY AD trial, the drug has a list price of $26,500 per year. Eisai recently initiated a rolling submission of a regulatory application with the US Food and Drug Administration seeking approval of a subcutaneous version of Leqembi that could be used as a weekly maintenance treatment, which would be more convenient than intravenous infusions.
European regulators, meanwhile, have taken a different view on the drug than their US counterparts. In July, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended against Leqembi's marketing authorization, stating that the "observed effect of Leqembi on delaying cognitive decline does not counterbalance the risk of serious side events associated with the medicine."
In the CLARITY AD study, ARIA due to edema occurred in 12.6 percent and 1.7 percent of patients who received Leqembi and placebo, respectively. ARIA due to hemosiderin deposition occurred in 16.9 percent of patients in the Leqembi arm and 8.9 percent of patients in the placebo arm. The European Commission has yet to make a final decision based on the CHMP's recommendation.
This is not NICE's final determination on Leqembi's availability in England. Sponsors have an opportunity to submit additional data on the drug's outcomes and cost effectiveness, and members of the public can also provide comment until Sept. 20, which NICE will then consider in its final recommendation.
An estimated 70,000 adults in England could be eligible for Leqembi if NICE supported its availability. In a statement, Biogen and Eisai said they are working with NICE, the Scottish Medicines Consortium, and the NHS to make Leqembi available to eligible Alzheimer's patients.