Alzheimer’s drug Lecanemab: EU Medicines Agency EMA rejects approval
Possible benefits of Lecanemab do not outweigh health risks for patients
The European Medicines Agency (EMA) has rejected the approval of the Alzheimer’s drug Leqembi (active substance: lecanemab) on July 26, 2024. The EMA’s Committee for Medicinal Products for Human Use (CHMP) justified its decision by stating that the benefits of Lecanemab do not outweigh the risks. In particular, the frequent occurrence – around 12.6% of participants in the trials developed ARIA-E and 17.3% suffered ARIA-H – of amyloid-related imaging abnormalities (ARIA), which include swelling and potential bleeding in the brain, was considered too serious. These side effects of the antibody lecanemab were considered a significant risk, especially in patients who are carriers of the ApoE4 gene, which could mean an increased susceptibility to such side effects.
In addition, the benefit of the active substance lecanemab was assessed as low. Leqembi did show an improvement on the Clinical Dementia Rating Scale (CDR-SB). However, many experts doubt whether the patients themselves feel any effect at all. In addition, the course of the disease is usually only delayed by a few months, which puts the benefits and risks in an unequal relationship. In reaching its decision, the CHMP also took into account the views of a scientific advisory group on neurology, which included experts such as neurologists and people with Alzheimer’s disease. The potential improvements were not considered sufficiently significant to justify approval and thus a market launch in the EU.
Leqembi to combat Alzheimer’s dementia directly for the first time
The antibody lecanemab, marketed under the name Leqembi, should be the first drug in Europe to treat the neurodegenerative disease and not just its symptoms. Leqembi aims to slow the progression of Alzheimer’s by removing deposits of the protein beta-amyloid from the brain and thus directly addressing the underlying disease processes.
There had already been controversial discussions among experts in the run-up to and during the approval process in the USA (see also: Lecanemab approved in the USA ). The safety concerns there led to Leqembi being given a “black box” warning, the strongest warning issued by the FDA. This is because the use of lecanemab requires close monitoring of patients through regular MRI examinations before and during treatment in order to detect signs of ARIA at an early stage and react accordingly. Additional diagnostic tests, the need for bi-weekly infusions and the associated high organizational effort as well as the costs of around US $ 25,000 per patient per year mean that the introduction of Leqembi in the USA has so far been rather slow.
DGN regrets EMA decision against Alzheimer’s antibody Lecanemab
The German Society of Neurology (DGN) regrets that no real-life data can be collected due to the lack of approval. The approval of the first Alzheimer’s antibody lecanemab would also have driven important health policy decisions on the infrastructure of early diagnosis and care, which may now be delayed, according to a current statement on the at least temporary end of lecanemab.
DGN calls for improved early diagnosis and preventive measures for Alzheimer’s patients
The DGN had hoped that various challenges and existing problems would have been addressed more quickly with the approval of Leqembi: Alzheimer’s antibodies such as lecanemab would have to be used in the early stages of the disease, when only mild cognitive impairment or mild dementia would be present, according to the society. As many of those affected have not yet been diagnosed at this stage, it would be necessary to raise awareness of early symptoms among the general public and doctors. In addition, amyloid pathology by cerebrospinal fluid analysis or PET scan is currently not sufficiently refinanced and does not cover the costs of neurological practices.
The current care structures are also not sufficient to treat all potential patients, which requires investment in treatment capacities. Healthcare policy would therefore have to create corresponding capacities.
Finally, the DGN warns that the potential of prevention must be further exploited, as up to 40 percent of all dementia could be prevented through a healthy lifestyle and the correction of risk factors. Preventive measures could slow down the progression of the disease to a similar extent as antibody therapy.
Sources:
https://www.ema.europa.eu/en/medicines/human/EPAR/leqembi
https://nachrichten.idw-online.de/2024/07/26/dgn-bedauert-chmp-empfehlung-gegen-die-ema-zulassung-des-ersten-alzheimer-antikoerpers-in-europa
