The TGA has rejected an application to register lecanemab in Australia for the treatment of mild cognitive impairment due to Alzheimer’s disease and early Alzheimer’s disease due to concerns over the safety of the drug.
Developed by pharmaceutical company Eisai, lecanemab (Leqembi) is a disease-modifying treatment that removes amyloid plaques in the brain and has been shown to slow the progress of cognitive decline by 27%.
The monoclonal antibody has been approved by regulatory authorities for use in the US, UK and several other countries, but was recently rejected by the European Medicines Agency in July and rejected for NHS funding by the UK’s National Institute for Health and Care Excellence (NICE) in August.
In a statement on the TGA website [link here] last week, the watchdog said the demonstrated efficacy of lecanemab did not outweigh the associated risks.
“In particular, clinical study data demonstrated that patients treated with LEQEMBI experienced a reduction in disease progression compared to those given a placebo, however this difference was not deemed significant enough to provide a meaningful clinical benefit or to outweigh the associated safety risks,” it said.
“In particular, the TGA delegate considered the frequent occurrence of amyloid-related imaging abnormalities (ARIA) in patients treated with LEQEMBI.”
Independent expert advice from the TGA’s Advisory Committee on Medicines supported the decision, the medicines watchdog said.
Updated safety results from a phase 3 trial in early Alzheimer’s disease published in Alzheimer’s Research & Therapy [link here] in May showed adverse events associated with lecanemab included ARIA with haemosiderin deposits (ARIA-H) microhaemorrhages (16.0%) and ARIA with oedema (ARIA-E; 13.6%). ARIA-E generally occurred within 3–6 months of treatment, was more common in ApoE e4 carriers (16.8%) and most common in ApoE ε4 homozygous participants (34.5%).
Given by IV infusion every two weeks, people treated with lecanamab are also recommended to have serial brain MRI imaging to monitor for abnormalities after the 5th, 7th, and 14th infusions and at one year.
The decision by the Australian Therapeutic Goods Association not to approve the amyloid removing therapy, Leqembi, is the right one. The tiny benefit doesn’t outweigh the risks. https://t.co/mDEnWVbs3L
— Dr Kate Gregorevic (@DrKGregorevic) October 17, 2024
While some neurologists and geriatricians have come out in support of the TGA’s decision, both the Australian Dementia Network and Dementia Australia described the rejection of the drug as a blow to Australian patients.
Dementia Australia CEO Professor Tanya Buchanan said the TGA decision meant that Australians living with Alzheimer’s disease in its early stages would not be able to access the same treatments as people living in other countries.
“Alzheimer’s disease is a progressive and ultimately fatal neurological condition so slowing decline when people are experiencing mild symptoms is incredibly important in supporting people to maintain quality of life for longer,” she said.
“Lecanemab is not a cure and is not for all people with a diagnosis of Alzheimer’s disease. Like many medicines it also comes with some significant risks. It is however, widely seen as an historic first step towards reducing the huge impact of Alzheimer’s disease and for people living with the condition it signified hope.”
Eisai Australia plans to appeal the decision.
Blood-based biomarkers for Alzheimer’s disease
Meanwhile, a study published in JAMA [link here] has shown that a blood-based biomarker test evaluated in primary and secondary care demonstrated more than 90% concordance with a clinical diagnosis of Alzheimer’s disease using cerebrospinal fluid Alzheimer’s disease biomarkers and amyloid PET scans.
Writing in an accompanying editorial [link here], US neurologists said the results for the blood test PrecivityAD2, which was clinically available in the US, provided important reassurance that the Alzheimer’s disease biomarker development pipeline was identifying strong biomarker candidates for clinical translation.
“Overall, this study marks a milestone in blood-based biomarker development, as a blood test for Alzheimer’s disease moves from the research world to dementia specialists and now into the hands of primary care physicians,” they said.
“It is truly humbling to reflect on the fact that verification of Alzheimer’s disease pathology, once purely the purview of the neuropathologist, can now be accomplished in the primary care clinic.”