Australia Regulatory Authority Declines Approval of Eisai’s Lecanemab for Early Alzheimer’s Disease

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Eisai and Biogen announced that the Therapeutic Goods Administration (TGA) of Australia has confirmed its initial decision to decline approval of lecanemab, a humanized anti-soluble aggregated amyloid-beta (Aβ) monoclonal antibody (mAb), for which the companies were seeking approval as a treatment for early Alzheimer’s disease (AD) in Australia. The TGA made the decision in October 2024 to not register lecanemab in Australia for this indication, according to a March 3, 2025 company press release issued by Eisai (1).

Eisai had requested a reconsideration of the decision in December 2024, in which it proposed to the TGA the apolipoprotein E4 (ApoE4) noncarrier and heterozygote indication for which the product was authorized by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom and the European Medicines Agency (EMA). The TGA, however, over the course of its reconsideration, proposed instead an alternative narrow therapeutic indication only for the ApoE4 noncarriers. The agency pointed out that an increasing number of ApoE4 alleles is a potential risk factor for amyloid-related imaging abnormalities (ARIA). The TGA did not agree that safety has been established for ApoE4 heterozygotes.

Eisai then proposed alternative indications, one of which aimed to maintain the ApoE4 noncarrier and heterozygote indication, but with heterozygotes treated in specialist centers under physician supervision by physicians with expertise in treating AD and monitoring for ARIA. The TGA rejected this proposal.

“We are extremely disappointed and surprised by the TGA’s decision and understand that the AD community in Australia may also feel disheartened, especially given that eleven countries and regions across the globe have granted marketing authorization,” said Lynn Kramer, MD, chief clinical officer at Eisai, in the press release (1). “We tried earnestly to reach a compromise with the TGA on an indication that would adequately represent the data in the application but were unfortunately unsuccessful at this time.”

The number of people in Australia living with dementia was an estimated to be approximately 411,000 in 2023, with a projected increase to approximately 849,000 by 2058 (2). AD is considered the most common cause of dementia and typically accounts for 60–70% of cases (3). There remains significant unmet need for new treatment options for slowing down progression of AD from early stages. Aβ is involved in the onset of the disease; it gradually aggregates in the brain over 15 to 20 years before symptoms appear. If untreated, insoluble plaques form, which are a pathological feature of AD.

Lecanemab works against AD in two ways, one, by continuously clearing protofibrils (most toxic Aβ species) and, two, by rapidly clearing plaque. These actions have been shown to reduce the rate of disease progression and to slow the decline of cognition and function.

“The TGA proposed a narrow indication that would limit access to only ApoE4 noncarriers. This indication would deny approximately two-thirds (~70%) of all potentially eligible patients access to a treatment that could slow the progression of AD. Eisai believes ApoE4 heterozygote carriers should at least also have access to lecanemab given the similar benefit-risk profile to the noncarrier population. Therefore, we could not accept this restrictive indication as it is not patient-centric. Given this outcome, we are deeply concerned that Australians living with Alzheimer’s disease will not have access to a treatment that slows the progression of early Alzheimer’s disease by targeting its underlying causes. Eisai remains committed to ensuring eligible Australians with early Alzheimer’s disease can access lecanemab and is exploring options to achieve this, including potentially seeking review by the Administrative Review Tribunal,” said Kramer in the press release.

Lecanemab is approved in the United States, Japan, China, South Korea, Hong Kong, Israel, the United Arab Emirates, the United Kingdom, Mexico, Macau and Oman. Regulatory filings are also underway in the European Union (EU) and 17 other countries and regions. In February 2025, the EMA’s Committee for Medicinal Products for Human Use reaffirmed a positive opinion for lecanemab in early AD, originally granted in November 2024 (4,5). The European Commission is proceeding with the decision-making process for lecanemab’s marketing authorization in the EU.

Eisai leads global development and regulatory submissions for lecanemab. It co-commercializes and co-promotes the product with Biogen.

References

1. Eisai. Eisai Receives Regulatory Review Outcome for Lecanemabas a Treatment for Early Alzheimer’s Disease in Australia. Press Release. March 3, 2024.
2. Australian Institure of Health and Welfare. Dementia. aihw.gov.au (accessed March 11, 2025).
3. World Health Organization. Dementia. who.int, March 15, 2023.
4. Eisai. The Committee for Medicinal Products for Human Use (CHMP) Reaffirms Positive Opinion for Lecanemab in Early Alzheimer’s Disease. Feb. 28, 2025.
5. Eisai. Eisai Receives Positive Opinion from the CHMP in the European Union for Lecanemab in Early Alzheimer’s Disease. Press Release, Nov. 15, 2024.