Lecanemab is an IgG1 monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta and reduces amyloid beta plaques.
Lecanemab reduced amyloid beta plaque in a time-dependent manner compared with placebo. The effect of lecanemab on amyloid beta plaque levels in the brain was evaluated using PET imaging visual read, and was quantified using the Standard Uptake Value Ratio (SUVR) method and the Centiloid scale. In Study 301, the mean change from baseline relative to placebo was statistically significant for lecanemab 10 mg/kg every 2 weeks at Week 79 in the indicated population (-59.437).
Exposure response analysis showed that observed amyloid PET SUVR decreased with the increase in lecanemab exposure. PK/PD analysis showed that changes in CSF Aβ1-42, plasma Aβ42/40 ratio and plasma p-tau181 correlated with the increase in exposure to lecanemab.
The immunogenicity of lecanemab has not been sufficiently evaluated due to limitation of ADA assay. The impact of ADA on pharmacokinetics, efficacy and safety has not been sufficiently evaluated.
The PK of lecanemab was characterized using a population PK analysis with concentration data collected from 1619 patients with Alzheimer's disease who received lecanemab in single or multiple doses. Steady state concentrations of lecanemab were reached after 6 weeks of 10 mg/kg every 2 weeks treatment and systemic accumulation was approximately 1.4-fold. The peak concentration (Cmax), and area under the plasma concentration versus time curve (AUC) of lecanemab increased dose proportionally in the dose range of 0.3 to 15 mg/kg following single dose.
Not applicable.
The mean value (95% CI) for volume of distribution at steady state is 5.52 (5.14 – 5.93) L.
Lecanemab is a mAb that targets soluble and insoluble aggregated forms of amyloid beta, and is not expected to be involved in cytokine modulated pathways.
Lecanemab is degraded by proteolytic enzymes in the same manner as endogenous IgGs. Lecanemab clearance (95% CI) is 0.370 (0.353-0.384) L/day. The terminal half-life is 5 to 7 days.
Lecanemab exhibits linear pharmacokinetics.
Lecanemab elimination occurs through normal degradative pathways for immunoglobulins, and the systemic clearance should not be affected by renal or hepatic impairment. Liver function biomarkers (ALT, AST, ALP, total bilirubin) and creatinine clearance did not affect the PK parameters of lecanemab.
Carcinogenicity studies have not been conducted.
Genotoxicity studies have not been conducted.
No studies in animals have been conducted to assess the effects of lecanemab on male or female fertility or developmental and reproductive function. No adverse effects on male or female reproductive organs were observed in a 39-week intravenous toxicity study in monkeys administered lecanemab weekly at doses up to 100 mg/kg (corresponding to plasma exposures 27-fold higher than in humans at the recommended dose). The relevance of these data to humans is limited since aggregate Aβ species are not present in healthy monkeys.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.