Lilly’s donanemab could bring new hope to Alzheimer’s patients in Australia following lecanemab rejection: GlobalData

Australia’s Therapeutic Goods Administration (TGA) has recently decided not to register lecanemab (Leqembi) for patients with mild cognitive impairment (MCI) or mild dementia of Alzheimer’s disease (AD). Despite lecanemab demonstrating slowing of disease progression in pivotal trials, concerns about its safety profile have led to TGA’s decision. Against this backdrop, Eli Lilly’s donanemab that has been submitted for review in October 2023 could bring new hope to Alzheimer’s patients in Australia following the rejection of lecanemab, says GlobalData.

Currently, lecanemab is approved in the US, UK, Japan, China, South Korea, Hong Kong, the UAE, and Israel. However, in July 2024, the European Medicines Agency (EMA) refused the marketing authorization for lecanemab, citing safety concerns.

The TGA has raised similar concerns and highlighted that lecanemab demonstrated a reduction in disease progression compared to placebo; however, this difference was not significant enough to provide a meaningful clinical benefit or to outweigh the associated safety risks, particularly the occurrence of amyloid-related imaging abnormalities (ARIA). However, Eisai/Biogen, the marketing company, has stated that they will request a reconsideration of this decision to TGA within 90 days.

Nadim Anwer, Pharma Analyst at GlobalData, states, “There is an urgent need for effective disease-modifying treatments and early interventions for dementia as it causes significant health issues and can have a major impact on patients’ and their families’ lives.”

Eli Lilly’s donanemab, another anti-aβ mAb in late-stage development as a direct competitor to lecanemab, is still under TGA’s review in Australia. Donanemab has a potential competitive edge over lecanemab as the first anti-amyloid drug that offers finite treatment; patients may stop treatment once amyloid has been reduced to minimal levels, enabling fewer infusions and lower treatment costs. However, clinical data demonstrated higher ARIA rates with donanemab (ARIA-E 24.0 per cent, ARIA-H 31.4 per cent) compared to lecanemab (ARIA-E 12.6 per cent, ARIA-H 17.3 per cent).

On the other hand, lecanemab has fallen short of expectations. The company initially had set a target of getting 10,000 US patients on lecanemab by the end of March 2024, but only about 5,600 patients had been enrolled for treatment by early April 2024, according to a registry by the Centers for Medicare & Medicaid Services.  Notably, additional diagnostic tests, twice-monthly infusions, regular brain scans, and safety concerns could be possible reasons for low adoption in the US.

According to GlobalData’s Pharmaceutical Intelligence Center, the diagnosed prevalent cases of AD are expected to increase at an annual growth rate (AGR) of 3.44 per cent from 0.19 million in 2023 to 0.23 million in 2028 in Australia.

There are four dementia-specific medications approved in Australia – donepezil, galantamine, rivastigmine, and memantine. These available drugs offer symptomatic relief and are neither disease-modifying nor providing a cure. 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 be available for Australian AD patients if approved by TGA.

Anwer concludes, “Though lecanemab is not a cure and has not been indicated for all AD patients, however, it is seen as a turning point to fight against dementia. The TGA’s decision has come as a disappointment to many Australians, as AD patients would not benefit from this disease-modifying therapy. However, hope remains for Australian AD patients, as donanemab may offer a new treatment. Moreover, TGA could reverse its lecanemab decision based on the growing clinical evidence from already approved markets, despite its slow initial adoption.”