Following the Therapeutic Goods Administration (TGA) in Australia's decision not to register lecanemab (Leqembi) for patients with mild cognitive impairment (MCI) or mild dementia of Alzheimer’s disease (AD), Eli Lilly’s donanemab, currently under review, emerges as a potential beacon of hope for Australian Alzheimer's patients. The rejection of lecanemab, despite demonstrating a slowing of disease progression in pivotal trials, was driven by concerns over its safety profile, specifically the occurrence of amyloid-related imaging abnormalities (ARIA).
Lecanemab is currently approved in the US, UK, Japan, China, South Korea, Hong Kong, the UAE, and Israel. However, the European Medicines Agency (EMA) refused marketing authorization for lecanemab in July 2024, also citing safety concerns.
The TGA highlighted that while lecanemab reduced disease progression compared to placebo, the difference was not significant enough to provide a meaningful clinical benefit or outweigh the associated safety risks, particularly ARIA. Eisai/Biogen, the marketing company for lecanemab, intends to request a reconsideration of this decision within 90 days.
The Promise of Donanemab
Nadim Anwer, Pharma Analyst at GlobalData, emphasized the urgent need for effective disease-modifying treatments for dementia, citing the significant health issues and impact on patients' and families' lives. Eli Lilly’s donanemab, a direct competitor to lecanemab, is in late-stage development and offers a potential competitive edge as the first anti-amyloid drug that offers finite treatment. This allows patients to potentially cease treatment once amyloid levels have been sufficiently reduced, leading to fewer infusions and lower treatment costs.
However, clinical data indicates higher ARIA rates with donanemab (ARIA-E 24.0%, ARIA-H 31.4%) compared to lecanemab (ARIA-E 12.6%, ARIA-H 17.3%). This safety profile will likely be a key consideration in the TGA's review process.
Lecanemab's Challenges
Lecanemab has faced challenges in uptake, with only about 5,600 patients enrolled for treatment in the US by early April 2024, falling short of the company's target of 10,000 patients by the end of March 2024. Additional diagnostic tests, twice-monthly infusions, regular brain scans, and safety concerns may contribute to this slow adoption.
Alzheimer's Disease Burden in Australia
According to GlobalData’s Pharmaceutical Intelligence Center, the diagnosed prevalent cases of AD in Australia are expected to increase at an annual growth rate (AGR) of 3.44%, from 0.19 million in 2023 to 0.23 million in 2028. Currently, available medications like donepezil, galantamine, rivastigmine, and memantine offer only symptomatic relief and are not disease-modifying.
There are 12 promising potentially disease-modifying drugs in late-stage (Phase III through Pre-Registration) development for AD in the US, EU, and Australia that could become available for Australian AD patients if approved by the TGA.
Hope for the Future
While lecanemab is not a cure and is not indicated for all AD patients, it is considered a turning point in the fight against dementia. The TGA’s decision is a disappointment for many Australians, but hope remains with donanemab. Furthermore, the TGA could reverse its lecanemab decision based on growing clinical evidence from already approved markets, despite its slow initial adoption.
