Two new drugs, lecanemab (Leqembi) and donanemab (Kisunla), representing the first treatments capable of slowing the progression of Alzheimer's disease, have ignited a significant medical controversy. Developed by Biogen/Eisai and Eli Lilly, respectively, these drugs have divided the medical community, with some hailing them as a breakthrough and others viewing them as another disappointment in a field plagued by failures.
While the United States has approved both lecanemab and donanemab, the European Union rejected lecanemab, casting doubt on donanemab's prospects for approval there. The UK has taken a middle ground, approving lecanemab but not making it available through the National Health Service.
Limited Efficacy and Significant Risks
Clinical trial data indicates that both drugs can reduce cognitive decline in patients with early-stage Alzheimer's by about 30%. However, critics argue that this benefit is marginal, especially when weighed against the potential risks, including brain swelling and bleeding, which have been fatal in rare cases. Rob Howard, a professor of old age psychiatry at University College London, stated, "The benefits are so tiny as to be practically invisible in an individual patient."
Cost and Accessibility Concerns
A major point of contention is the exorbitant cost of these treatments. A 2023 study estimated that treating all eligible patients in the EU with lecanemab would cost 133 billion euros ($148 billion). This raises concerns about equitable access, with some fearing that only wealthy individuals will be able to afford the drugs, potentially creating disparities in treatment availability.
The Amyloid Plaque Hypothesis
The development of lecanemab and donanemab is rooted in the amyloid plaque hypothesis, which posits that amyloid plaques in the brain are a primary driver of Alzheimer's disease. This theory gained prominence following a 1992 article by British biologist John Hardy. While many previous drugs targeting amyloid plaques failed, lecanemab and donanemab have shown some success in slowing cognitive decline, reigniting the debate about the role of amyloid in Alzheimer's.
Differing Perspectives and Future Directions
Despite the controversies, many neurologists advocate for the use of lecanemab and donanemab, believing they can offer patients valuable additional months of autonomy. They also suggest that earlier intervention, made possible by advancements in diagnostic techniques, could enhance the drugs' effectiveness.
However, some experts caution against relying solely on amyloid-targeting therapies. A doctor working for Eli Lilly, who wished to remain anonymous, criticized Biogen for overstating the benefits of its previous Alzheimer's treatment, Aduhelm, which was later withdrawn after a controversial approval. This expert emphasized the need to explore other mechanisms underlying Alzheimer's disease, suggesting that single-target treatments may have limited impact. As a group of experts wrote in the Journal of Prevention of Alzheimer's Disease last month, it is unlikely that "single-target treatments will achieve substantially larger effects" than lecanemab and donanemab, but the new drugs are a "critical step" in Alzheimer's treatment.
