New Alzheimer’s Drug Rejected by European Medicines Agency Committee

A European Medicines Agency (EMA) committee has recommended the refusal of EU marketing authorization for Alzheimer’s drug lecanemab (Leqembi), which was only last year given the green light for approval by the US Food and Drug Administration (FDA).

The EMA’s human medicines committee (CHMP) considered that the drug’s benefits did not outweigh the risks of potentially serious side effects.

Targeting amyloid beta

Lecanemab is an anti-amyloid antibody drug that has already earned approval in several countries, including the US. Clinical trials suggest it can modestly slow cognitive decline for patients in the early stages of Alzheimer’s.

The drug works by targeting a protein called amyloid beta, which is thought to lead to the disease’s cognitive symptoms by forming clumps – called plaques – in the brain. This hypothesis has led to many years of research devoted to developing amyloid-targeting drugs in the hopes of slowing the progression of the disease.

Some of these drugs have been approved by some medicines agencies – such as the FDA’s approval last year – due to their modest effect on disease progression. However, there are some concerns over potentially dangerous side effects called amyloid-related imaging abnormalities (ARIA), which can cause small microbleeds or clots in the brain.

While ARIA can occur in the brains of people with Alzheimer’s who have not received anti-amyloid drugs, evidence suggests they may present a higher risk. Many ARIA cases are asymptomatic, but a small number of cases can be life-threatening, necessitating the inclusion of the FDA’s most stringent boxed warning on lecanemab’s label.

But why, given the similar information presented to these agencies, have they decided on different recommendations?

“This outcome highlights a significant cultural disparity in how risk and innovation are perceived across different regions,” said Prof. Bart De Strooper, professor of Alzheimer’s disease at University College London. “While Europe tends to view the glass as half empty, countries such as the USA, China and Japan see it as half full.”

Glass half full, or a measured approach?

Despite the difference in decisions, the EMA’s more cautious approach has been praised by some experts: “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,” said Prof. Robert Howard, professor of old age psychiatry at University College London.

“Though this decision will disappoint some patients and their families, I think it is a responsible one given the available evidence,” said Dr. Sebastian Walsh, a National Institute for Health and Care Research Doctoral Fellow at the University of Cambridge.

However, others argue patients could be missing out on valuable treatments that could improve their quality of life: “Today is a somber 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,” said De Strooper.

“I have to say I am disappointed in the decision to not grant a license to lecanemab for the treatment of Alzheimer’s disease,” said Prof. John Hardy, professor of neuroscience at University College London. “The EMA (in contrast to the FDA) has taken the view that the risk of ARIA outweighs the clinical benefit.”

“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.”

More drugs are in the pipeline

But there is still hope; the drug has earned approval in several countries after many years of failed drugs and clinical trials for the field. Additional data from these countries could be reviewed by the EMA at a later date as clinical use of lecanemab grows.

Beyond lecanemab, there is still some optimism to be had in Alzheimer’s research; over 125 experimental drugs are currently under investigation in clinical trials – showing the drug development landscape is promising, and more treatments are hopefully on the horizon.

“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,” said Prof. Tara Spires-Jones, president of the British Neuroscience Association and director of the Centre for Brain Science Discovery at the University of Edinburgh. “Each discovery brings us closer to new and better treatments.”