The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued an unfavourable opinion on the application for authorisation of lecanemab (Leqembi) for the treatment of Alzheimer’s disease, considering that the benefits observed when administering this medicine in delaying cognitive decline do not outweigh the risks of serious side effects, including amyloid-related imaging abnormalities (ARIA), such as inflammation and possible brain bleeding, which can be fatal. A study published in Neurology in May 2023 even linked its use with accelerated loss of brain volume.
Lecanemab is a drug developed by Biogen and Eisai that is administered intravenously and that on July 6 last year received final approval from the American Food and Drug Administration (FDA) in the United States, which had initially approved it on an accelerated basis. The agency concluded that the evidence of its clinical efficacy was sufficient for its commercialization. This drug is approved for early stages of cognitive impairment or dementia with confirmed presence of beta amyloid pathology.
Clinical efficacy results from the pivotal phase III Clarity AD trial, published in The New England Journal of Medicine, show that administration of the drug every 15 days can slow cognitive decline by 27% after 18 months of treatment. This figure represents a significant reduction in the degree of deterioration compared to placebo. In addition, the drug significantly reduces amyloid deposits by 50% after one year of treatment.
Dementia currently affects around 55 million people worldwide, and Alzheimer’s is the most prevalent type of dementia, accounting for 60-70% of cases. Cases are expected to continue to rise, which is why it is so important to find therapies that prevent its onset or delay the associated cognitive decline and disability. Lecanemab is one of the new drugs aimed at removing beta amyloid plaques already approved in the United States.
Donanemab (Kisunla) is another similar Alzheimer’s drug developed by Lilly that also has final FDA approval and is indicated for monthly intravenous administration in patients with early stages of dementia and confirmed beta amyloid. This drug can also cause serious side effects such as brain swelling and small strokes.
The decision of the European Medicines Agency has generated controversy
Several experts have expressed their opinion on the EMA’s decision not to authorise this new treatment for early Alzheimer’s in statements to SMC Spain. “The phase III clinical trial of lecanemab showed that it does what it is supposed to do: it reduces toxic amyloid in the brain and slows down cognitive decline. From a scientific point of view, it was an important step forward. However, the magnitude of the effect was modest, which was compounded by significant side effects, such as inflammation and brain haemorrhages that caused the death of some people,” said Tara Spires-Jones, president of the British Association for Neuroscience, director of the Centre for Brain Science Discovery at the University of Edinburgh and head of the UK Dementia Research Institute Group in Edinburgh (UK).
“The EMA decision will be a disappointment for many, but there are reasons to remain hopeful. Lecanemab has shown that it is possible to slow the progression of the disease and research is working. Now we need to redouble our efforts to discover new and safer treatments. Scientists around the world are tackling this issue from different angles: from stopping the movement of toxic tau proteins through the brain to protecting synapses, which allow neurons to communicate. Each discovery brings us closer to new and better treatments,” he adds.
“The imaging abnormality seen in treated patients is often asymptomatic or presents only minor headaches as symptoms, but is occasionally associated with brain hemorrhages.”
For his part, John Hardy, Professor of Neuroscience and Group Leader at the UK Dementia Research Institute, University College London, said in statements to the same media: “I have to say that I am disappointed by the decision not to grant a license to lecanemab for the treatment of Alzheimer’s disease. The EMA (unlike the FDA) has considered that the risk of ARIA [Anomalías de imagen relacionadas con el amiloide] outweighs the clinical benefit. The imaging abnormality seen in treated patients is often asymptomatic or presents only with minor headaches as symptoms, but is occasionally associated with cerebral hemorrhages.”
“The question of whether the undoubted statistical benefit of the treatment is worth the risk of serious, though rare, side effects is always a difficult one with any treatment, and on this occasion the EMA in Europe and the FDA in the US have come to different conclusions when presented with similar data. I am sure we will now see wealthy people with early-stage Alzheimer’s flying to the US or other jurisdictions for treatment. I expect this decision will be reviewed as US doctors and others collect and report on real-world experience with the (very similar) lecanemab and dononemab treatments,” he adds.
For her part, Mercè Boada Rovira, neurologist and medical director of Ace Alzheimer Center Barcelona, told SMC Spain: “Today the EMA has taken the decision not to register Leqembi™ in the EU. This decision brings with it two major concerns, both for the clinical, medical and healthcare community, as well as for the research community. Patients in Europe will be discriminated against, they will not have the same options and opportunities as patients in other countries. And in terms of research and investment in research, Europe will also be in second place.”
“We will once again go through the desert. We will be in the middle of a drought, once again. And this will have an impact on the quality of patients and their families, on the research capacity of Spanish researchers and clinicians, and in itself it will impoverish our entire health system by not having the opportunity to collect data from the real world (real world evidence) to understand, to improve and to change the frequency-dose of new products that may appear and to invest. To invest above all in research into treatments that are much more effective than this one, undoubtedly, for the benefit of our citizens.”
“This is the position of the Ace Foundation, the clinical department and the research department, and we regret this decision by the EMA.”
