Therapeutic Goods Administration decides not to register lecanemab in Australia

Rhea-AI Summary

BioArctic AB (NASDAQ: BIOA B) announced that Australia's Therapeutic Goods Administration (TGA) has declined to approve lecanemab for early Alzheimer's disease treatment. The TGA rejected both the initial application in October 2024 and a December 2024 reconsideration request that proposed limiting the treatment to ApoE4 noncarriers and heterozygotes.

The TGA suggested a narrower indication for ApoE4 noncarriers only, citing safety concerns for ApoE4 heterozygotes. Despite Eisai's proposal for treating heterozygotes in specialist centers under expert supervision, the TGA maintained its rejection.

This decision affects approximately 411,000 people living with dementia in Australia as of 2023, with this number projected to reach 849,000 by 2058. Lecanemab, which works by clearing toxic Aβ protofibrils and plaques, has already received approval in 11 markets including the US, Japan, China, and the UK, with pending applications in the EU and 17 other regions.

Positive

• 11 major markets already approved the drug
• EU approval process progressing positively
• Pending applications in 17 additional countries/regions

Negative

• TGA rejection blocks access to Australian market
• Delayed market entry in Australia impacts potential revenue
• Safety concerns for ApoE4 heterozygotes limit patient population

Insights

Pharmaceutical Industry Expert

The TGA's rejection of lecanemab for early Alzheimer's disease represents a significant market access barrier for BioArctic and Eisai in Australia. The decision hinged specifically on safety concerns related to ARIA (Amyloid-Related Imaging Abnormalities) risk in patients with the ApoE4 gene variant, particularly rejecting the proposed compromise to treat heterozygotes in specialist centers under expert supervision.

This setback occurs in a substantial potential market with 60-70% of Australia's 411,000 dementia patients likely having Alzheimer's disease, projected to reach 849,000 by 2058. Lecanemab's dual mechanism—continuously clearing toxic Aβ protofibrils while rapidly removing plaque—has demonstrated ability to slow disease progression, making this rejection particularly impactful for patients facing a progressive neurodegenerative condition.

Despite this regional setback, lecanemab maintains strong global momentum with approvals across 11 markets including major pharmaceutical territories like the US, Japan, China, and UK. The EU approval appears likely following the CHMP's reaffirmed positive opinion in February 2025. For BioArctic specifically, which originated the antibody based on Professor Lars Lannfelt's Arctic mutation discovery, the Nordic commercialization rights remain a key business opportunity as joint commercialization preparations continue with Eisai.

Regulatory Affairs Specialist

The TGA's decision reveals a notable regulatory divergence in safety risk assessment between Australia and other major markets. While the EMA and UK MHRA accepted Eisai's proposed indication for both ApoE4 noncarriers and heterozygotes, Australia's regulator took a more conservative stance, suggesting an indication restricted only to ApoE4 noncarriers based on ARIA risk concerns.

Eisai's reconsideration request and subsequent compromise proposal—to maintain the broader indication but with additional safeguards for heterozygotes through specialist centers and expert physician oversight—represents a standard regulatory negotiation strategy, but proved unsuccessful in this case. The company's announced intention to potentially pursue Administrative Review Tribunal assessment signals a continuing commitment to the Australian market rather than abandonment.

This case highlights the increasingly complex regulatory landscape for amyloid-targeting therapies in Alzheimer's disease, where benefit-risk assessments can vary significantly between jurisdictions despite identical clinical data packages. With 17 additional regulatory applications pending globally, companies in this space must prepare for potential similar divergence in other markets, potentially necessitating market-specific risk management strategies. The TGA decision could influence regulatory thinking in markets with similarly conservative approach to novel neurological treatments.

STOCKHOLM, Sweden, March 3, 2025 /PRNewswire/ -- BioArctic AB's (publ) (NASDAQ: BIOA B) (STOCKHOLM: BIOA B) partner Eisai announced today that the Therapeutic Goods Administration (TGA) of Australia has declined the approval of lecanemab (generic name) as a treatment for early Alzheimer's disease (AD) (mild cognitive impairment due to AD and mild AD dementia). 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.

In October 2024, the TGA made the decision not to register lecanemab in Australia for the treatment of patients with early AD. In December 2024, Eisai requested reconsideration of the decision, proposing to the TGA the same apolipoprotein E4 (ApoE4) noncarrier and heterozygote indication that was agreed by the Medicines and Healthcare products Regulatory Agency (MHRA) and European Medicines Agency (EMA). In the course of the reconsideration of the initial decision, the TGA proposed an alternative narrow therapeutic indication only for ApoE4 noncarriers as an increasing number of ApoE4 alleles is a potential risk factor for ARIA. They did not agree that safety has been established for ApoE4 heterozygotes. Eisai proposed alternative indications, one of which was to maintain the ApoE4 noncarrier and heterozygote indication, but with heterozygotes treated in specialist centers and supervised by physicians with expertise in treatment of AD and monitoring for ARIA; however, the TGA rejected Eisai's proposal. 

"We are very disappointed with the TGA's decision. Foremost it is sad for all patients, caregivers and healthcare professionals in Australia who will now have to wait longer for a treatment which can effectively change the course of this devastating disease. We know that for these patients, time is what they value the most and denying them a treatment which has been shown to delay the onset of more severe stages of the diseases is of course not what they or we had hoped for," said Gunilla Osswald, CEO at BioArctic.

In Australia, the number of people living with dementia was estimated to be approximately 411,000 in 2023, and is reported to increase to approximately 849,000 by 2058.^[1] AD is considered the most common cause of dementia, typically accounting for 60-70% of cases.^[2] AD progresses in stages that increase in severity over time, and each stage of the disease presents different challenges for those living with AD and their care partners. There is a significant unmet need for new treatment options that slow down the progression of AD from its early stage and reduce the overall burden on people affected by AD and society.

Aβ which is involved in the onset of AD, gradually aggregates in the brain 15 to 20 years before symptoms appear, eventually forming insoluble plaques, a pathological feature of AD. AD is a progressive, relentless disease caused by a continuous underlying neurotoxic process that begins before and continues after plaque removal.^[3],[4],[5] Lecanemab works to fight AD in two ways: continuously clearing protofibrils, the most toxic Aβ species, and rapidly clearing plaque. This mechanism has been shown to reduce the rate of disease progression and to slow cognitive and functional decline.

Lecanemab has so far been approved in 11 markets including the U.S., Japan, China and the United Kingdom. Regulatory filings for the treatment have been made in the EU and 17 other countries and regions In the EU, in February 2025, the Committee for Medicinal Products for Human Use reaffirmed its positive opinion for lecanemab in early AD, adopted in November 2024, and the European Commission is proceeding with the decision-making process for lecanemab's marketing authorization.

Leqembi is the result of a long-standing collaboration between BioArctic and Eisai, and the antibody was originally developed by BioArctic based on the work of Professor Lars Lannfelt and his discovery of the Arctic mutation in Alzheimer's disease. Eisai is responsible for the clinical development, applications for market approval and commercialization of Lecanemab for Alzheimer's disease. BioArctic has the right to commercialize Leqembi in the Nordic region together with Eisai and currently, the two companies are preparing for a joint commercialization in the region.  

The information was released for public disclosure, through the agency of the contact person below, on March 3, 2025, at 09:00 CET.   

For further information, please contact:  
Oskar Bosson, VP Communications and IR 
E-mail:  oskar.bosson@bioarctic.com 
Phone: +46 70 410 71 80 

Charlotte af Klercker, Director Communications and Sustainability
E-mail: charlotte.afklercker@bioarctic.com  
Phone: +46 73 515 09 70

About lecanemab (Leqembi^®) 

Lecanemab is the result of a strategic research alliance between BioArctic and Eisai. It is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). 

Lecanemab is approved in the U.S., Japan, China, United Kingdom, and several other markets for the treatment of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and mild AD dementia. Lecanemab's approvals in these countries, as well as the CHMP's positive opinion in November 2024, were primarily based on Phase 3 data from Eisai's global Clarity AD clinical trial, in which it met its primary endpoint and all key secondary endpoints with statistically significant results. Eisai has also submitted applications for regulatory approval of lecanemab in several other countries and regions.

A supplemental Biologics License Application (sBLA) for less frequent intravenous maintenance dosing was approved by the U.S. Food and Drug Administration (FDA) in January 2025. In January 2025, the rolling submission of a Biologics License Application (BLA) for maintenance dosing of a subcutaneous auto injection formulation, which is being developed to enhance convenience for patients, was accepted in the U.S., with PDUFA date August 31, 2025. 

Since July 2020, Eisai's Phase 3 clinical study (AHEAD 3-45) with lecanemab in individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. The study was fully recruited in October 2024. AHEAD 3-45 is a four-year study conducted as a public-private partnership between the Alzheimer's Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health and Eisai. Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing and includes lecanemab as the backbone anti-amyloid therapy. 

About the collaboration between BioArctic and Eisai 

Since 2005, BioArctic has a long-term collaboration with Eisai regarding the development and commercialization of drugs for the treatment of Alzheimer's disease. The most important agreements are the Development and Commercialization Agreement for the lecanemab antibody, which was signed 2007, and the Development and Commercialization agreement for the antibody Leqembi back-up for Alzheimer's disease, which was signed 2015. In 2014, Eisai and Biogen entered into a joint development and commercialization agreement for lecanemab. Eisai is responsible for the clinical development, application for market approval and commercialization of the products for Alzheimer's disease. BioArctic has the right to commercialize lecanemab in the Nordic region under certain conditions and is currently preparing for commercialization in the Nordics together with Eisai. BioArctic has no development costs for lecanemab in Alzheimer's disease and is entitled to payments in connection with regulatory approvals, and sales milestones as well as royalties on global sales. 

About BioArctic AB 

BioArctic AB (publ) is a Swedish research-based biopharma company focusing on innovative treatments that can delay or stop the progression of neurodegenerative diseases. The company is the originator of Leqembi^® (lecanemab) – the world's first drug proven to slow the progression of the disease and reduce cognitive impairment in early Alzheimer's disease. Leqembi has been developed together with Eisai. BioArctic has a broad research portfolio within Alzheimer's disease, Parkinson's disease, ALS and enzyme deficiency diseases. Several of the projects utilize the company's proprietary BrainTransporter™ technology, which improves the transport of drugs into the brain. BioArctic's B share (BIOA B) is listed on Nasdaq Stockholm Large Cap.

For more information, please visit www.bioarctic.com. 

^[1] Dementia in Australia https://www.aihw.gov.au/reports/dementia/dementia-in-aus/contents/population-health-impacts-of-dementia/prevalence-of-dementia

^[2] World Health Organization. Dementia Fact Sheet. March 2023. Available at: https://www.who.int/news-room/fact-sheets/detail/dementia

^[3] Eisai presents full results of lecanemab Phase 3 confirmatory Clarity AD study for early Alzheimer's disease at Clinical Trials on Alzheimer's Disease (CTAD) conference. Available at: https://www.eisai.co.jp/news/2022/news202285.html

^[4] van Dyck, H., et al. Lecanemab in Early Alzheimer's Disease. New England Journal of Medicine. 2023;388:9-21. https://www.nejm.org/doi/full/10.1056/NEJMoa2212948

^[5] Hampel H, Hardy J, Blennow K, et al. The amyloid-β pathway in Alzheimer's disease. Mol Psychiatry. 2021;26(10):5481-5503

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Therapeutic Goods Administration decides not to register lecanemab in Australia

 

 

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SOURCE BioArctic

FAQ

Why did the TGA reject lecanemab (BIOA B) for Alzheimer's treatment in Australia?

TGA rejected lecanemab due to safety concerns, particularly for ApoE4 heterozygotes, despite proposals to limit treatment to specialist centers under expert supervision.

How many markets have approved BioArctic's lecanemab as of March 2025?

Lecanemab has been approved in 11 markets, including the United States, Japan, China, and the United Kingdom.

What is the mechanism of action for BioArctic's lecanemab in treating Alzheimer's?

Lecanemab works by clearing toxic Aβ protofibrils and plaques from the brain, reducing disease progression and slowing cognitive decline.

How many Australians could be affected by TGA's decision to reject lecanemab?

The decision affects approximately 411,000 Australians living with dementia as of 2023, projected to increase to 849,000 by 2058.