Eisai's Leqembi Faces a Rival: Lilly's Donanemab Nearing Approval for Alzheimer's Treatment

Eisai, which developed a new Alzheimer's treatment globally after about 20 years last year, has faced a strong competitor just one year after its launch.

The US Food and Drug Administration (FDA) advisory committee unanimously recommended the approval of 'donanemab,' an Alzheimer's treatment developed by US pharmaceutical company Eli Lilly, on June 10th. While the advisory committee's decision is not legally binding, the FDA usually follows its recommendations, so donanemab is likely to be launched in the US and Japan this year. This signifies a rapid entry into competition for Lecanemab, the Alzheimer's treatment launched by Eisai in 2023.

GlobalData, a UK market research firm, predicts that the sales of Eisai and Lilly's drugs will each reach approximately $5 billion by 2029. It is believed that the choice of which drug patients and doctors will choose will depend on the differences in detailed characteristics and the sales strategies of the two companies going forward.

Both drugs share the mechanism of inhibiting the progression of Alzheimer's by removing the protein 'beta-amyloid' accumulated in the brain, but they differ in patient burden, administration targets, and other aspects.

Based on the results of clinical trials conducted so far, Lilly's donanemab has shown a slightly higher risk of side effects such as cerebral hemorrhage. It is also only applicable to patients with a certain level of 'tau' protein in the brain. In the donanemab clinical trial, administration was continued every four weeks, and administration was discontinued when a certain level of efficacy was observed.

On the other hand, Eisai's Lecanemab requires administration every two weeks, and the timing at which administration can be discontinued is not yet clear. For Eisai, Lecanemab is a crucial drug responsible for the company's future growth. Eisai's current flagship product is the anti-cancer drug 'Lenvima,' which accounted for approximately 40% of Eisai's 741.8 billion yen in sales in 2023. However, Lenvima's substance patent expires in 2026, and generic drugs are likely to enter the market afterward. Lecanemab, the Alzheimer's treatment, is expected to be the 'successor drug' that will take over after Lenvima's patent expiration.

Meanwhile, the National Center for Geriatrics and Gerontology in Japan is also providing information on Lilly's donanemab. The research center is paying attention to the high possibility that donanemab can effectively remove amyloid plaques in the brain. In 2021, based on the results of the Phase 2 clinical trial 'TRAILBLAZER-ALZ,' which evaluated the safety and efficacy of donanemab, Lilly applied to the US FDA for accelerated approval. However, the FDA withheld accelerated approval for donanemab in January 2023. This was because there was insufficient "data from 100 people who received donanemab for a minimum of 12 months" needed to confirm the safety of donanemab. However, the FDA did not express any concerns about the efficacy of donanemab.

Lilly continued the Phase 3 clinical trial to collect the necessary data and applied for full approval to the US FDA in July 2023 and to the Ministry of Health, Labour and Welfare in Japan in September of the same year.

The difference between Lecanemab and donanemab lies in the type of amyloid-beta aggregates they bind to. Lecanemab binds to both 'protofibrils,' intermediate-sized amyloid-beta aggregates, and larger amyloid plaques. On the other hand, donanemab selectively binds to amyloid plaques that have accumulated in the brain and have been marked with 'pyroglutamylation' over time. This difference may be one of the reasons why donanemab is more effective at removing accumulated amyloid plaques in the brain. Conversely, Lecanemab may be more effective at binding to and removing amyloid plaques at the initial stage of accumulation in the brain.

Currently, the review process for donanemab's approval is underway in the US and Japan, and we must await the results. However, by understanding the characteristics of Lecanemab and donanemab and utilizing these two antibody drugs appropriately, it may be possible to increase safety and efficacy while reducing dosage, duration, and cost. Further research is needed in the future.