Abstract
Background
The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) whitethorn initiate oregon potentiate pathologic processes successful Alzheimer’s disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with precocious affinity to Aβ soluble protofibrils, is being tested successful persons with aboriginal Alzheimer’s disease.
Methods
We conducted an 18-month, multicenter, double-blind, signifier 3 proceedings involving persons 50 to 90 years of property with aboriginal Alzheimer’s illness (mild cognitive impairment oregon mild dementia owed to Alzheimer’s disease) with grounds of amyloid connected positron-emission tomography (PET) oregon by cerebrospinal fluid testing. Participants were randomly assigned successful a 1:1 ratio to person intravenous lecanemab (10 mg per kilogram of assemblage value each 2 weeks) oregon placebo. The superior extremity constituent was the alteration from baseline astatine 18 months successful the people connected the Clinical Dementia Rating–Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater impairment). Key secondary extremity points were the alteration successful amyloid load connected PET, the people connected the 14-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog14; range, 0 to 90; higher scores bespeak greater impairment), the Alzheimer’s Disease Composite Score (ADCOMS; range, 0 to 1.97; higher scores bespeak greater impairment), and the people connected the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL; range, 0 to 53; little scores bespeak greater impairment).
Results
A full of 1795 participants were enrolled, with 898 assigned to person lecanemab and 897 to person placebo. The mean CDR-SB people astatine baseline was astir 3.2 successful some groups. The adjusted least-squares mean alteration from baseline astatine 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95% assurance interval [CI], −0.67 to −0.23; P<0.001). In a substudy involving 698 participants, determination were greater reductions successful encephalon amyloid load with lecanemab than with placebo (difference, −59.1 centiloids; 95% CI, −62.6 to −55.6). Other mean differences betwixt the 2 groups successful the alteration from baseline favoring lecanemab were arsenic follows: for the ADAS-cog14 score, −1.44 (95% CI, −2.27 to −0.61; P<0.001); for the ADCOMS, −0.050 (95% CI, −0.074 to −0.027; P<0.001); and for the ADCS-MCI-ADL score, 2.0 (95% CI, 1.2 to 2.8; P<0.001). Lecanemab resulted successful infusion-related reactions successful 26.4% of the participants and amyloid-related imaging abnormalities with edema oregon effusions successful 12.6%.
Conclusions
Lecanemab reduced markers of amyloid successful aboriginal Alzheimer’s illness and resulted successful moderately little diminution connected measures of cognition and relation than placebo astatine 18 months but was associated with adverse events. Longer trials are warranted to find the efficacy and information of lecanemab successful aboriginal Alzheimer’s disease. (Funded by Eisai and Biogen; Clarity AD ClinicalTrials.gov number, NCT03887455.)
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Sign InFunding and Disclosures
Supported by Eisai (regulatory sponsor), with partial backing by Biogen.
Disclosure forms provided by the authors are disposable with the afloat substance of this nonfiction astatine NEJM.org.
This nonfiction was published connected November 29, 2022, astatine NEJM.org.
A data sharing statement provided by the authors is disposable with the afloat substance of this nonfiction astatine NEJM.org.
We convey the proceedings participants and their families, arsenic good arsenic each the investigators and tract unit who made the proceedings imaginable (see the Supplementary Appendix for a database of collaborators); the members of the information and information monitoring committee and the raters; Lars Lannfelt and the unit of BioArctic for their aboriginal probe connected lecanemab; the unit of the objective probe enactment Worldwide Clinical Trials for their ongoing enactment successful conducting the trial; and J. David Cox (Mayville Medical Communications) and Lisa Yarenis (Eisai) for penning and editing assistance with an earlier mentation of the manuscript, successful accordance with Good Publication Practice 4 ethical guidelines.
Author Affiliations
From the Alzheimer’s Disease Research Unit, Yale School of Medicine, New Haven, CT (C.H.D.); Eisai, Nutley, NJ (C.J.S., M.K., D.L., L.R., S.D., M.I., L.D.K.); the Alzheimer’s Therapeutic Research Institute, University of Southern California, San Diego (P.A.); Washington University School of Medicine successful St. Louis, St. Louis (R.B.); the Memory, Aging, and Cognition Center, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (C.C.); Eisai, Hatfield, United Kingdom (M.G.); Toronto Memory Program, Toronto (S.C.); Medical Faculty Mannheim, University of Heidelberg, Central Institute of Mental Health, Mannheim, Germany (L.F.); Katayama Medical Clinic, Okayama (S.K.), and the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, and the National Center of Neurology and Psychiatry, Tokyo (T.I.) — each successful Japan; Barrow Neurological Institute, Phoenix, AZ (M.S.); Toulouse Gerontopole University Hospital, Université Paul Sabatier, INSERM Unité 1295, Toulouse, France (B.V.); and Alzheimer’s Research and Treatment Center, Wellington, FL (D.W.).
Dr. van Dyck tin beryllium contacted astatine [email protected] oregon astatine the Alzheimer’s Disease Research Unit, Division of Aging and Geriatric Psychiatry, Yale School of Medicine, 1 Church St., 8th Fl., New Haven, CT 06510.
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