July 26, 2024

expert reaction to EMA decision on lecanemab for Alzheimer’s disease

Scientist comment on the EMA decision on the use of lecanemab for Alzheimer’s disease. 

Prof Robert Howard, Professor of Old Age Psychiatry, UCL, said:

“Based on the clinical trial evidence of only very modest efficacy, that would just not be noticeable in an individual person with Alzheimer’s disease and that cannot be considered clinically meaningful by any objective measure, and the real risks of harms from brain swelling and bleeding, EMA have made the right decision in my opinion. 

“We all want to see treatments for this terrible condition. I have worked in the field for more than 30 years and am as impatient as anyone for something to offer my patients and their families. But I don’t want them to be given false hope or to be exposed to a treatment that is more likely to harm than to help. EMA have looked carefully at the trial data and their decision reflects their conclusion that lecanemab is more likely to harm people with Alzheimer’s disease than to help them. On behalf of my patients and colleagues, I would want to thank them for their work and for coming to what must have been a difficult decision to reach and to express.”

Prof Jonathan Schott, Chief Medical Officer at Alzheimer’s Research UK, said:

“Lecanemab is not a cure for Alzheimer’s disease, but evidence from clinical trials suggests that it can slow progression in people with mild forms of the disease, in whom it leads to benefits in quality of life and reduces impact on carers.

“While it is of course vital to balance benefits and potentially serious side-effects, the EMA’s recommendation runs counter to the decision reached by other G7 nations like the US and Japan, whose regulators have already given the green light to this drug and have embedded risk management plans to address potential side effects.

“Attention will now turn to the UK’s regulator – the MHRA – which is expected to announce a decision on lecanemab imminently. This announcement can’t come too soon for people with Alzheimer’s disease in Great Britain who for now must wait to see whether the UK will forge ahead with innovative medicines, or follow the EMA and adopt a more cautious approach.

“While disappointing, today’s news is a reminder both of how far we have come, and how much work there still is to do. Research has led to huge advances in our understanding of how Alzheimer’s disease starts and develops, and ever better ways of making an early and accurate diagnosis. There are now more than 160 clinical trials underway testing over 125 experimental treatments for Alzheimer’s across the globe, with over 30 in the final phase of development. It really is a matter of when, not if, we can offer people with dementia the new treatments they so desperately need.”

Prof Michele Vendruscolo, Director of the Chemistry of Health Laboratory and Professor of Biophysics, University of Cambridge, said:

“In reaching its negative decision, the EMA balanced Leqembi’s cognitive benefits against its potentially severe side effects, which may include brain swelling and bleeding. However, hope remains for Alzheimer’s patients in Europe. The EMA could reverse its stance based on the growing clinical experience in the US, China and Japan, where the drug has been approved. Furthermore, all the three disease-modifying drugs approved to date by the FDA to treat Alzheimer’s disease target amyloid beta. This focusses further efforts on this target. We could thus expect increasingly potent drugs against this amyloid beta to be developed, progressively increasing our ability to fight this devastating disease.”

Mark MacDonald, Associate Director of Evidence, Policy and Influencing at Alzheimer’s Society, said: 

“We’re disappointed that lecanemab has not met the safety and effectiveness requirements to be licensed in Europe. While we fully respect the decision, we acknowledge it will be really difficult news for people in Europe who may have been eligible for this drug. 

“Here in the UK, Alzheimer’s Society awaits decisions from the MHRA and NICE on both lecanemab and donanemab as regulators scrutinise the evidence around these treatments. 

“Whatever the regulators decide, we remain at an important and exciting moment. There are currently 164 active clinical trials for Alzheimer’s disease and we expect more treatments to be submitted for MHRA approval in the future. We are on the cusp of major scientific breakthroughs beginning to improve the outlook for those with the disease. 

“That makes it even more important that we improve diagnosis. A third of people in the UK with dementia don’t have a diagnosis at all, let alone one with the timeliness and accuracy required to unlock access to the new treatments on the horizon.   

“New, ambitious dementia diagnosis rate targets should be set, accompanied by funded plans to deliver early, accurate diagnosis at scale.”  

Prof Bart De Strooper, Professor in Alzheimer’s Disease at UCL and UKDRI

“I regret to read the unfortunate yet not unexpected decision regarding the approval of Lecanemab/Lequembi. This outcome highlights a significant cultural disparity in how risk and innovation are perceived across different regions. While Europe tends to view the glass as half-empty, countries such as the USA, China, and Japan see it as half-full.

“This conservative approach means that patients and doctors eager to explore a proven effective drug are now denied access. With no current therapies available, it’s disheartening to think that if we had applied such caution in the past, particularly with cancer drugs and their severe side effects, we might still be without cancer treatments today.

“Once again, Europe positions itself as a follower, allowing other nations to determine the optimal benefit-to-side-effect balance through practical use of Lecanemab in clinical settings. This decision marks a setback for patients and a blow to clinical research in a field long overlooked by Europe.

Today is a sombre day for the patients who could have benefited from Lecanemab and for the advancement of clinical research that has been stifled for too many years.”

Dr Sebastian Walsh, NIHR Doctoral Fellow, University of Cambridge, said:

“Though this decision will disappoint some patients and their families, I think it is a responsible one given the available evidence. The EMA rejection is based upon their view that small reduction in the amount of cognitive decline experienced over 18 months in the trial was not a clear enough benefit to justify the side effects experienced. Further challenges for these drugs come when you consider that the people in the drug trials were very carefully selected, and most patients in real-world settings have more complex disease which may reduce the expected benefit, and increase the likelihood of side effects. There is also the cost, the eligibility checks, the brain scan monitoring, and the need to have infusions every 2-4 weeks – which means we must ask whether limited resources (not just money but also trained staff) could produce better results for patients if used elsewhere, for example on providing holistic person-centred care. I expect the UK regulators to take a similar view, but we will have to wait for their decision.”

Dr Ivan Koychev, Principal Clinical Investigator at the United Kingdom Dementia Platform and member of the department of Psychiatry, University of Oxford, Warneford Hospital, said:

“EMA’s decision on lecanemab reflects the complex considerations that had to be taken into account. On the one hand, this is a novel therapeutic option that appears to affect the causes of a devastating condition for which we only currently have symptomatic treatment. An approval would have been a positive sign for further innovation in dementia drug development and create impetus for redesigning the dementia care pathways across the EU and elsewhere. On the other hand, the cognitive benefits for those with syndromal stage of Alzheimer’s disease are at best modest and occur in the context of significant side effects. In addition, the investment required to deploy this novel treatment for dementia is substantial: an economic analysis showed that the cost of the drug alone equals half of the current medication budget of the EU (assuming it was given to everyone who is eligible).

“In my view, the decision creates pressure on EMA to create clear guidance on what clinically meaningful benefit in syndromal Alzheimer’s disease is. This will help to maintain the momentum created by the amyloid clearance therapies break-through and offer hope for those living with or at-risk for dementia.”

Prof John Hardy, Professor of Neuroscience and Group Leader at the UK Dementia Research Institute, University College London (UCL), said:

“I have to say I am disappointed in the decision to not grant a license to Lecanemab for the treatment of Alzheimer’s disease. The EMA (in contrast to the FDA) has taken the view that the risk of ARIA outweighs the clinical benefit. The imaging abnormality seen in treated patients is usually either without symptoms or with only minor, headaches as symptoms, but is occasionally associated with brain haemorrhages. The question of whether the undoubted statistical benefit of treatment is worth the risk of serious, though rare side effects is always difficult with any treatment and on this occasion the EMA in Europe and the FDA in the US have reached different conclusions when presented with similar data. I am sure we will now see rich people with early Alzheimer’s disease flying to the US or other jurisdictions for treatment. My guess would be that this decision will be revisited as US clinicians and others gather and report real world experience with both lecanemab and the (very similar) dononemab treatments.”

Prof Tara Spires-Jones, President of the British Neuroscience Association, Director of the Centre for Brain Science Discovery at the University of Edinburgh and Group Leader at the UK Dementia Research Institute, said:

“The Phase III clinical trial of lecanemab showed that it does what it’s supposed to; it reduces toxic amyloid in the brain and slows cognitive decline. Scientifically, this was an important step forwards. However, the size of the effect was modest, and coupled with that there were significant side effects, including swelling and brain bleeds leading to death in a few people.

“The EMA’s decision will come as a disappointment to many, but there are reasons to remain hopeful. Lecanemab has shown that it is possible to slow down disease progression, and research does work. Now we need to ramp up our efforts to discover new and safer treatments. Scientists around the world are tackling this from different angles – from stopping toxic “tau” proteins moving through the brain, to protecting synapses, which allow neurons to communicate. Each discovery brings us closer to new and better treatments.”

Declared interests

Prof Robert Howard: No conflicts.

Prof Michele Vendruscolo: I have no conflicts of interest to declare.

Prof Bart de Strooper: I have been consultant and advisor for many pharmaceutical companies, including EISAI, and I have been founder of two spin off companies (Augustine TX and Muna TX).

Dr Sebastian Walsh: No COI

Dr Ivan Koychev: received a grant and speaker fees from Novo Nordisk. He is a paid medical advisor for digital healthcare (Five Lives SAS, Cognes, Cognetivity, Lola Speaks) and biotechnology (CFDX Ltd) companies in the dementia space.

Prof Sir John Hardy: has consulted for Eli Lilly and Eisai

Prof Tara Spires-Jones: “I have no conflict with this issue. The full statement of economic interests is: Scientific Advisory Boards: Scottish Brain Sciences, Cognition Therapeutics, Race Against Dementia; Trustee of Charities: Guarantors of Brain, British Neuroscience Association; Consulting/Speaking Fees: Jay Therapeutics, Sanofi, AbbVie; Laboratory Research Funding: CoEN Fellowship from the United Kingdom Medical Research Council, United Kingdom Institute of Dementia Research, Alzheimer’s Society.”

For all other experts, no reply to our request for DOIs was received.