Lecanemab reduces clinical decline in early Alzheimer’s disease
Presenter: Christopher van Dyck, MD, Yale School of Medicine, New Haven, CT
A study to confirm safety and efficacy of lecanemab in participants with early Alzheimer's disease (Clarity AD). Presented April 25, 2023.
Lecanemab, an investigational monoclonal antibody agent, was found to produce moderate declines on measures of cognition and function at 18 months in patients with early stage Alzheimer disease (AD), according to Clarity AD clinical trial results presented by Christopher van Dyck, MD, of the Yale School of Medicine, New Haven, CT. Lecanemab binds with high affinity to amyloid-beta soluble protofibrils to reduce the accumulation of soluble and insoluble aggregated amyloid-beta, which may initiate or potentiate the pathologic processes in AD.
The Clarity AD trial is a large multicenter, double-blind, parallel-group, phase III clinical trial investigating lecanemab for the treatment of mild cognitive impairment due to AD and mild AD (collectively known as early AD) in patients with confirmed amyloid pathology in the brain, van Dyck said.
Lecanemab treatment significantly reduced the clinical decline on the global cognitive and functional scale, CDR-SB, by 27% versus planebo at 18 months, which represents a treatment difference in the score change of -0.45 in the analysis of the intent-to-treat population. Starting as early as 6 months and continuing across all time points, the treatment showed highly statistically significant changes in CDR-SB from baseline compared with placebo.
The Food and Drug Administration gave lecanemab accelerated approval in January 2023 based on amyloid clearance. The FDA is expected to make a decision on full approval by July 2023, said van Dyck. However, it is uncertain whether the Centers for Medicare and Medicaid Services will cover the drug. Last year, Medicare sharply limited its coverage of a similar drug, aducanumab, citing risks and unclear benefit.
The Clarity AD study randomized 1,795 patients with early AD to receive 10 mg/kg lecanemab biweekly (898 patients) or placebo (897 patients) for 18 months. The baseline characteristics of both placebo and lecanemab groups were similar and well-balanced.
All key secondary endpoints were also met with highly statistically significant results compared with placebo. Key secondary endpoints were the changes from baseline at 18 months compared with placebo of treatment in amyloid levels in the brain measured by amyloid positron emission tomography, the AD Assessment Scale-cognitive subscale14 (ADAS-cog14), AD Composite Score (ADCOMS), and the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL).
Consistent benefits were seen in quality of life and caregiver burden across different scales, said van Dyck.
The incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), an adverse event associated with anti-amyloid antibodies, was 12.6% in the lecanemab group and 1.7% in the placebo group. The incidence of symptomatic ARIA-E was 2.8% in the lecanemab group and 0% in the placebo group. The ARIA-H (ARIA cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis) rate was 17.3% in the lecanemab group and 9% in the placebo group.
In conclusion van Dyck said, “Lecanemab treatment met all primary and secondary endpoints versus placebo at 18 months, with highly significant differences starting at 6 months. The safety profile of lecanemab is acceptable, with lower rates of ARIA-E in Clarity-AD compared to other published studies of anti-amyloid beta monoclonal antibodies.”
Biomarker studies revealed that lecanemab improved both of the essential biological features of AD — amyloid beta and tau — by positron emission tomography, cerebrospinal fluid and plasma, indicating biological disease modification. The AHEAD study is investigating whether earlier, pre-symptomatic and longer intervention may be associated with greater effect sizes.
References
van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer's disease. N Engl J Med 2023; 388(1):9-21. doi:10.1056/NEJMoa2212948. Epub 2022 Nov 29.
Reish NJ, Jamshidi P, Stamm B, et al. Multiple cerebral hemorrhages in a patient receiving lecanemab and treated with t-PA for stroke. N Engl J Med 2023;388(5):478-479. doi:10.1056/NEJMc2215148. Epub 2023 Jan 4.
van Dyck C. A study to confirm safety and efficacy of lecanemab in participants with early Alzheimer's disease (Clarity AD). Presented at the 75th Annual Meeting of the American Academy of Neurology, April 25, 2023.
Disclosures
Christopher van Dyck: Advisor/Consultant for Roche, Eisai, Ono Pharmaceutical, and Cerevel Therapeutics. Yale University received grant support from Eli Lilly, Biogen, Roche, Biohaven, UCB, Janssen Pharmaceuticals, Eisai, Genentech, and Cerevel Therapeutics.