Lecanemab for Alzheimer's disease: new hope or another false dawn?

wchh.onlinelibrary.wiley.com 4 I Progress in Neurology and Psychiatry I Vol. 27 Iss. 1 2023 Since the development of the ‘amyloid hypothesis1–3 there has been considerable effort in developing treatments that target the build-up of amyloid beta (Aβ) plaques in the brain thought to be responsible for Alzheimer’s disease (AD). Over the past 15 years, much of this research has focussed on developing monoclonal antibodies as potential disease modifying treatments (DMTs) targeting Aβ.4 However, a number of trials of similar molecules did not meet the primary endpoint or were pulled midway after interim futility analyses,5–7 leading to questions about whether this was the right approach given the complex and multifactorial pathogenesis of AD. An exception to this was the USA’s Food and Drug Administration (FDA) accelerated approval for aducanumab in June 2021, which we reviewed here previously.8 Accelerated approval was designed to allow for earlier authorisation of drugs that are intended to treat serious conditions where the initial evidence showed the potential to address an unmet clinical need. There is still a requirement for phase 4 confirmatory trials, which in the case of aducanumab are ongoing. The decision to grant accelerated approval for aducanumab was controversial due to doubts regarding clinical efficacy – that it was based on post hoc analysis of data, and also safety concerns. The decision led to several members of the FDA advisory team resigning in protest.9