New Alzheimer’s drug data highlights increased benefits over three years, but EMA rejects approval citing safety concerns.
New data presented at the Alzheimer’s Association International Conference 2024 (AAIC) has revealed the potential long-term benefits of the Alzheimer’s drug lecanemab. While the findings highlight improved cognition and function in patients over three years without additional safety concerns [1], the European Medicines Agency (EMA) has rejected the drug’s license, citing insufficient benefit-risk balance [2]. It is a juxtaposition that highlights the complexity and challenges of progressing Alzheimer’s therapeutics – balancing the urgent need to address this debilitating condition against the risks of side effects and the broader implications for healthcare systems and patients.
Longevity.Technology: The situation reflects a broader tension in the field of Alzheimer’s research and treatment. On the one hand, there is an urgent and undeniable need for effective therapies to manage this ever-growing global health challenge – there are nearly 7 million Americans living with Alzheimer’s, and by 2050, this number is projected to rocket to nearly 13 million, with health and long-term care costs for people living with dementia projected to reach nearly $1 trillion by the same date [3].
On the other hand, however, any new treatment must demonstrate a favorable balance of benefits and risks, especially in a vulnerable patient population. Moreover, the availability of treatments for early Alzheimer’s necessitates an equally robust system for early detection and accurate diagnosis, a current gap in many healthcare systems – approximately 75% of all dementia cases remain undiagnosed [4].
The new data from the AAIC indicates that lecanemab, which is marketed under the brand name Leqembi, continues to offer significant benefits to patients in the early stages of Alzheimer’s disease. According to the study, over 50% of patients with no or low levels of tau protein – an indicator of Alzheimer’s progression – showed improved cognitive and functional outcomes after three years of treatment. These results are particularly noteworthy as they suggest that the benefits of lecanemab treatment may increase with longer usage, challenging the notion that its efficacy plateaus after initial plaque clearance. The drug’s dual action – clearing amyloid plaques and highly toxic protofibrils – supports neuronal function and appears to slow the spread of tau across all brain regions, offering a unique therapeutic approach.
Dr Richard Oakley, Associate Director of Research and Innovation at Alzheimer’s Society, responded positively to these findings, emphasizing that the study marks the first time longer-term benefits of lecanemab have been documented without additional safety concerns. He highlighted that “a small subgroup of participants in the very earliest stages of Alzheimer’s disease were found to have either no decline or an improvement in memory and thinking skills,” suggesting that early and accurate diagnosis is critical for maximizing the drug’s benefits. Oakley also stressed the importance of continual treatment and called for further data to confirm these initial observations. He noted that while lecanemab is approved in several countries, including the United States, China, Japan, and South Korea, the UK is still awaiting a decision from its Medicines and Healthcare products Regulatory Agency (MHRA) [5].
Despite these promising developments, the EMA’s Committee for Medicinal Products for Human Use (CHMP) recently issued a negative opinion on lecanemab. The EMA’s decision was grounded in concerns over the drug’s safety profile, particularly regarding amyloid-related imaging abnormalities (ARIA), which include brain swelling and bleeding. The regulatory body pointed out that, although these side effects were mostly non-serious, some cases involved significant complications such as large brain bleeds requiring hospitalization. The EMA concluded that “the benefits of lecanemab did not counterbalance the risk of serious side effects,” thereby preventing its approval in the European Union (EU) at this time [2].
This decision has sparked disappointment among advocates and stakeholders within the Alzheimer’s community. Lynn Kramer, MD, Chief Clinical Officer at Eisai, the pharmaceutical company, which in partnership with Biogen, is behind lecanemab, expressed frustration over the EMA’s rejection.
“We are extremely disappointed by the CHMP’s negative opinion and understand that this may also be disappointing for the wider Alzheimer’s disease (AD) community,” he said, emphasizing the pressing need for innovative treatment options that address the underlying causes of disease progression. Kramer also noted Eisai’s commitment to re-examining the CHMP opinion and said the company aims to collaborate with relevant authorities to ensure that lecanemab becomes available to eligible patients in the EU as swiftly as possible.
Progress in Alzheimer’s therapeutics seems to take as many steps forwards as backwards, and the contrasting views on lecanemab highlight the ongoing debate this space. While promising data suggest potential long-term benefits, safety concerns cannot be overlooked, and the way forward will require a nuanced approach that prioritizes patient safety while striving to address the devastating impact of Alzheimer’s disease on individuals and society.
[1] https://investors.biogen.com/news-releases/news-release-details/new-clinical-data-demonstrates-three-years-continuous-treatment
[2] https://www.ema.europa.eu/en/medicines/human/EPAR/leqembi
[3] https://www.alz.org/alzheimers-dementia/facts-figures
[4] https://www.brightfocus.org/alzheimers/article/alzheimers-disease-facts-figures
[5] https://apigateway.agilitypr.com/distributions/history/16ef5743-5a71-4de1-9b40-44347db5bc8c
