On September 27, Eisai and Biogen announced topline results from their Phase III CLARITY AD trial (NCT03887455) evaluating lecanemab, an anti-amyloid beta (Aβ) monoclonal antibody (mAb), for the treatment of patients with early Alzheimer’s disease (AD). After multiple past failures and the controversial approval and chaotic launch of Biogen’s anti-Aβ mAb Aduhelm (aducanumab), lecanemab has finally demonstrated in a large-scale pivotal trial that targeting Aβ can be a successful way to treat AD.
In Clarity AD, lecanemab met the primary endpoint, Clinical Dementia Rating-Sum of Boxes (CDR-SB), demonstrating a reduced clinical decline of 27% compared with placebo at 18 months of treatment. Treatment with lecanemab started showing statistical significance compared with placebo at six months. Additionally, all key secondary endpoints were also met with statistical significance. Demonstrating reduced clinical decline is particularly important to lecanemab’s prospects, as it demonstrates that it has a significant clinical effect, unlike Aduhelm, which failed to demonstrate this in its own clinical trials and was approved by the FDA based on the surrogate endpoint of Aβ clearance.
A known side effect of amyloid-lowering therapies is the development of amyloid-related imaging abnormalities (ARIAs), including ARIA related to underlying vasogenic edema (ARIA-E). In Clarity AD, the rate of ARIA-E was 12.5%, with symptomatic ARIA-E in just 2.8% of patients. Although the incidence of ARIA could be a potential barrier for lecanemab, as it requires close monitoring of patients receiving the drug, it represents a significant improvement when compared with Aduhelm, for which 35% of patients taking the approved dose of the drug developed ARIA-E in its pivotal Phase III trials, ENGAGE (NCT02477800) and EMERGE (NCT02484547). Not only does this give lecanemab a competitive advantage over Aduhelm but also over future potential anti-Aβ mAb competitors, Eli Lilly’s donanemab and Roche ’s gantenerumab: based on available Phase II data, both drugs showed rates of ARIA-E closer to Aduhelm than lecanemab.
Although Aduhelm should have a first-to-market advantage among the anti-Aβ mAbs, GlobalData expects lecanemab to be significantly more successful due to this Phase III data showing improved efficacy and safety. Additionally, Aduhelm has been facing uptake issues due to the US Centers for Medicare and Medicaid Services (CMS ) limiting Medicare reimbursement of the product to only AD patients participating in randomized controlled trials. GlobalData forecasts strong sales for lecanemab across the eight major markets (US, France, Germany, Italy, Spain, UK, Japan, and China), reaching sales of $2.76bn by 2030.