Leqembi Receives Approval in Japan for the Treatment of Alzheimer's Disease: A Milestone in Slowing Cognitive Decline

On September 25th, Weichai and Bojian jointly announced that Leqembi injection (200mg, 500mg, lecanemab) has been approved in Japan for the treatment of mild cognitive impairment (MCI) and mild dementia caused by Alzheimer's disease (AD). Leqembi is a humanized monoclonal antibody of immunoglobulin G1 (IgG1) that targets soluble and insoluble forms of aggregated Aβ. Its target of action is β-amyloid, the primary component of amyloid plaques, which are the hallmark of AD in the brain. Clinical trials have clearly demonstrated measurable and meaningful benefits of removing amyloid from the brain in early-stage AD patients.

Leqembi is the first and only treatment approved through traditional authorization to modify the underlying course of Alzheimer's disease. By selectively binding and eliminating the most toxic Aβ aggregates (oligomers) that cause neurotoxicity in AD, Leqembi slows down the progression of the disease and delays cognitive and functional decline.

In December 2020, Bojian submitted a New Drug Application (J-NDA) for Leqembi to the Ministry of Health, Labour and Welfare (MHLW) in Japan, and the application for market approval was granted priority review qualification in January 2023. Japan becomes the second country to approve Leqembi after the United States received traditional approval in July 2023.

The approval of Leqembi in Japan is based on the data from a large global Phase III clinical trial called Clarity AD conducted by Weichai, where Leqembi met the primary endpoint and all key secondary endpoints with statistically significant results, confirming its clinical benefits. The primary endpoints were the global cognition and function scale and the Clinical Dementia Rating-Sum of Boxes (CDR-SB).

In the confirmatory Phase III study, Clarity AD, conducted by Weichai, consistency of results was demonstrated across different cognitive and functional scales and subgroups (ethnicity, race, comorbidities). Based on CDR assessment, Leqembi treatment reduced the risk of progressing to the next stage of the disease by 31% (hazard ratio: 0.69).

Based on observed data and extrapolation of the slope analysis conducted up to 30 months on CDR-SB, Leqembi treatment at 25.5 months was equivalent to the level at 18 months with placebo, indicating a delay in disease progression by 7.5 months. Simulations based on Phase II trial data suggest that Leqembi could potentially slow disease progression by 2.5 to 3.1 years, helping patients to maintain a longer period in the early stages of AD. Furthermore, Leqembi also preserves health-related quality of life in patients and reduces caregiver burden (reducing worsening scores by 23-56%).

Collectively, evidence in cognition and function, disease progression, health-related quality of life, and caregiver burden demonstrates the positive benefits of Leqembi treatment for patients, caregivers, clinicians, and society.

Weichai will conduct post-marketing surveillance (all-case monitoring) of all patients receiving Leqembi, in accordance with the approval conditions set by the Ministry of Health, Labour and Welfare in Japan, until a certain number of patient data is accumulated after market launch. In addition, appropriate use of Leqembi will be promoted based on the package insert, and training materials will be developed for healthcare professionals to assist in the management and monitoring of amyloid-related imaging abnormalities (ARIA).

Weichai is the lead developer and global regulatory filer for Leqembi, and Weichai and Bojian will jointly commercialize and promote Leqembi, with Weichai having the final decision-making authority. In Japan, Weichai and Bojian will jointly promote Leqembi, with Weichai acting as the marketing authorization holder for the product. BioArctic has the rights to commercialize lecanemab in the Nordic region, and currently, Weichai and BioArctic are preparing for joint commercialization in that area.