Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer's Disease.
J Prev Alzheimers Dis
; 9(2): 197-210, 2022.
Article
em En
| MEDLINE
| ID: mdl-35542991
ABSTRACT
BACKGROUND:
Alzheimer's disease is a progressive, irreversible, and fatal disease for which accumulation of amyloid beta is thought to play a key role in pathogenesis. Aducanumab is a human monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta.OBJECTIVES:
We evaluated the efficacy and safety of aducanumab in early Alzheimer's disease.DESIGN:
EMERGE and ENGAGE were two randomized, double-blind, placebo-controlled, global, phase 3 studies of aducanumab in patients with early Alzheimer's disease.SETTING:
These studies involved 348 sites in 20 countries.PARTICIPANTS:
Participants included 1638 (EMERGE) and 1647 (ENGAGE) patients (aged 50-85 years, confirmed amyloid pathology) who met clinical criteria for mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease dementia, of which 1812 (55.2%) completed the study. INTERVENTION Participants were randomly assigned 111 to receive aducanumab low dose (3 or 6 mg/kg target dose), high dose (10 mg/kg target dose), or placebo via IV infusion once every 4 weeks over 76 weeks. MEASUREMENTS The primary outcome measure was change from baseline to week 78 on the Clinical Dementia Rating Sum of Boxes (CDR-SB), an integrated scale that assesses both function and cognition. Other measures included safety assessments; secondary and tertiary clinical outcomes that assessed cognition, function, and behavior; and biomarker endpoints.RESULTS:
EMERGE and ENGAGE were halted based on futility analysis of data pooled from the first approximately 50% of enrolled patients; subsequent efficacy analyses included data from a larger data set collected up to futility declaration and followed prespecified statistical analyses. The primary endpoint was met in EMERGE (difference of -0.39 for high-dose aducanumab vs placebo [95% CI, -0.69 to -0.09; P=.012; 22% decrease]) but not in ENGAGE (difference of 0.03, [95% CI, -0.26 to 0.33; P=.833; 2% increase]). Results of biomarker substudies confirmed target engagement and dose-dependent reduction in markers of Alzheimer's disease pathophysiology. The most common adverse event was amyloid-related imaging abnormalities-edema.CONCLUSIONS:
Data from EMERGE demonstrated a statistically significant change across all four primary and secondary clinical endpoints. ENGAGE did not meet its primary or secondary endpoints. A dose- and time-dependent reduction in pathophysiological markers of Alzheimer's disease was observed in both trials.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article