Last year, Eisai, which developed a new Alzheimer's treatment worldwide after nearly 20 years, is facing a strong competitor only a year after its launch.

On June 10, the US Food and Drug Administration (FDA) advisory committee unanimously recommended approval of 'donanemab,' an Alzheimer's treatment developed by US pharmaceutical company Lilly. The committee's decision is not legally binding, but the FDA usually follows the committee's opinion, so donanemab is likely to be launched in the US and Japan this year. This means that Lilly will be entering the competition with Eisai's Alzheimer's treatment 'Lecanemab,' which was launched in 2023.

GlobalData, a UK market research firm, predicts that Eisai and Lilly's drug sales will reach approximately $5 billion each by 2029. It remains to be seen which drug patients and doctors will choose, depending on subtle differences in features and the future sales strategies of the two companies.

Both drugs share the mechanism of removing 'beta amyloid,' a protein that accumulates in the brain, to inhibit Alzheimer's progression, but they differ in terms of patient burden, administration target, and other aspects.

According to the clinical trial results 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 trials, administration was continued every four weeks, and administration was discontinued when a certain level of effectiveness was observed.

On the other hand, Eisai's Lecanemab needs to be administered every two weeks, and it is not yet clear when administration can be discontinued. For Eisai, Lecanemab is a crucial entity responsible for the company's future growth. Eisai's current flagship product is the anti-cancer drug 'Lenvima,' which accounted for about 40% of Eisai's sales of 741.8 billion yen in 2023. However, Lenvima will face the expiration of its material patent in 2026, and generic drugs are likely to enter the market after that. Alzheimer's treatment Lecanemab is expected to be the 'successor drug' responsible for the period after the expiration of Lenvima's patent.

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 possibility that donanemab can effectively remove amyloid plaques in the brain. In 2021, Lilly applied for accelerated approval from the US FDA based on the results of a Phase 2 clinical trial 'TRAILBLAZER-ALZ' that evaluated the safety and efficacy of donanemab. However, the FDA withheld accelerated approval of donanemab in January 2023. This was because there was not enough data, "data from 100 people who received donanemab for at least 12 months," to confirm the safety of donanemab. However, the FDA did not express concerns about the efficacy of donanemab.

Lilly continued with Phase 3 clinical trials to collect the necessary data, and submitted an application for full approval to the US FDA in July 2023, and also submitted an application for approval to the Ministry of Health, Labour and Welfare in Japan in September of the same year.

The difference between Lecanemab and donanemab is 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 labeled with 'pyroglutamylation' over time. This difference may be one of the reasons why donanemab more effectively removes amyloid plaques accumulated in the brain. Conversely, Lecanemab may be more effective in binding and removing amyloid plaques that are beginning to accumulate in the brain.

Currently, the review process for approval of donanemab is underway in the US and Japan, and we must await the results. However, if we understand the characteristics of Lecanemab and donanemab well and use the two antibody drugs appropriately, there is a possibility that we can increase safety and efficacy while reducing dosage, duration, and costs. Further research is needed.