Eisai and Biogen reported positive data from a Phase III clinical trial of the anti-amyloid antibody lecanemab (BAN2401) to treat Alzheimer’s disease (AD)-associated mild cognitive impairment and mild AD with established amyloid pathology in the brain.
According to topline results, lecanemab met its primary endpoint of change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) over 18 months in the 1,795-patient Phase III CLARITY AD trial (NCT03887455). Lecanemab treatment reduced clinical decline relative to a placebo by 27% along CDR-SB, representing a score change of -0.45 (p=0.00005) in the analysis of Intent-to-treat population. CDR-SB is an 18-point scale that combines cognitive and functional outcomes to measure the severity of dementia symptoms.
Lecancemab is the first of a series of high-profile AD trial readouts expected at the end of 2022 and early 2023. The antibody targets amyloid plaque accumulation in the brain, a popular yet controversial therapeutic target in AD. Biogen ‘s Aduhelm (aducanumab), which also targets amyloid plaque, has faltered in the market after gaining FDA accelerated approval in July 2021.
Clarity AD also met all key secondary endpoints of ariation from baseline in amyloid positron emission tomography (PET) using Centiloids, AD Assessment Scale-Cognitive Subscale 14 (ADAS-cog14), and AD Composite Score (ADCOMS) at 18 months. In the lecanemab and placebo arms, the occurrence of amyloid-related imaging abnormalities-oedema/effusion (ARIA-E) were 12.5% and 1.7%, respectively.
Eisai plans to seek marketing authorisations in Japan and Europe, as well as a traditional approval for the antibody in the US by the end of March next year.
In yesterday’s press release, Eisai CEO Haruo Naito said: “The lecanemab Clarity AD study results prove the amyloid hypothesis, in which the abnormal accumulation of Aβ in the brain is one of the main causes of Alzheimer’s disease when targeted with a protofibril-binding therapy. Eisai believes these findings will create new horizons in the diagnosis and treatment of Alzheimer’s disease as well as further activate innovation for new treatment options.”
An investigational humanised monoclonal antibody, lecanemab attaches to neutralise and remove soluble, toxic amyloid-beta (Aβ) aggregates (protofibrils). In November last year, the companies reported that Aduhelm (aducanumab-avwa) substantially lowered plasma p-tau181 in Phase III EMERGE and ENGAGE trials.