The second Alzheimer's drug was rejected by NICE on the same day it was approved in the UK

On October 23, 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) approved Eli Lilly's anti-amyloid beta (Aβ) monoclonal antibody (mAb) Kisunla for the treatment of patients with mild cognitive impairment (MCI) or mild Alzheimer's disease disease approved in Great Britain. However, on the same day of its approval, the National Institute for Health and Care Excellence (NICE) announced that it would not initially adopt Kisunla for use in the UK's National Health Service (NHS), citing an unfavorable risk-benefit profile and poor cost-effectiveness.

Although NICE's decision was disappointing for many Alzheimer's patients, it was not unexpected. This is the second time in 2024 that, on the same day that the MHRA approved a new disease-modifying therapy (DMT) for Alzheimer's disease, NICE's initial recommendation was not to recommend the drug on the NHS. In August 2024, Eisai/Biogen's anti-Aβ mAb Leqembi became the first DMT approved for MCI and mild Alzheimer's disease in the UK, but is also currently not recommended by NICE due to lack of cost-effectiveness and safety concerns.

The approval of Kisunla was based on data from the phase III TRAILBLAZER-ALZ 2 trial. Patients treated with Kisunla demonstrated 35% slower cognitive and functional decline at 18 months compared to placebo-treated patients, as measured by the integrated primary endpoint Alzheimer's disease rating scale. In Leqembi's pivotal Phase III trial (Clarity AD), it reduced clinical decline compared to placebo by 27% at 18 months as measured by the primary endpoint, Clinical Dementia Rating-Sum of Boxes. Although these DMTs represent a major breakthrough in the Alzheimer's market, their effect is modest. Therefore, there remains uncertainty among physicians and regulators as to whether this reduction is large enough for patients to notice a real difference in their perception that justifies the cost of treatment. In the United States, where both drugs are marketed, annual treatment costs are about $25,000 for Leqembi and $36,000 for Kisunla, according to GlobalData's POLI pricing database. In addition, a known side effect of the anti-Aβ mAb drug class is the development of amyloid-related imaging abnormalities (ARIAs), including ARIAs associated with underlying vasogenic edema (ARIA-E). For Kisunla in TRAILBLAZER-ALZ 2, the ARIA-E rate was 24.0% and the symptomatic ARIA-E rate was 6.1%. Leqembi has the advantage as the rate of ARIA-E in Clarity AD was 12.5% ​​and the rate of symptomatic ARIA-E was 2.8%. To monitor ARIA risk, magnetic resonance imaging (MRI) is required before treatment, and additional MRIs are recommended before subsequent infusions, increasing the overall cost of therapy.

Importantly, NICE's decisions are not final for either drug. NICE had requested further evidence on the extent and benefits of the drugs' effects, as well as the overall cost. For Kisunla, this is particularly important to understand because this medication is not designed to be taken indefinitely. Questions therefore remain about the average duration of treatment with the drug and the consequences if treatment is stopped. However, this means that the total lifelong therapy costs for Kisunla could be significantly cheaper than for Leqembi. The MHRA has planned a post-approval safety study to assess the long-term effects of the medicines. Additional real-world experience, particularly from the United States, where both Leqembi and Kisunla are approved and prescribed, will also be critical to the success of both drugs.

Leading data and analytics company GlobalData forecasts that Leqembi and Kisunla will generate sales of approximately $3.5 billion and $2.2 billion, respectively, in the eight major pharmaceutical markets (US, France, Germany, Italy, Spain, UK, Japan and China). could achieve $0 billion by 2030.