Lecanemab: Appropriate Use Recommendations - 21/11/24

Doi : 10.14283/jpad.2023.30

J. Cummings ^1,^12,^⁎ , L. Apostolova ², G.D. Rabinovici ³, A. Atri ⁴, P. Aisen ⁵, S. Greenberg ⁶, S. Hendrix ⁷, D. Selkoe ⁸, M. Weiner ⁹, R.C. Petersen ¹⁰, S. Salloway ¹¹

For the Alzheimer’s Disease and Related Disorders Therapeutics Work Group

¹ Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas (UNLV), Las Vegas, NV, USA

² Departments of Neurology, Radiology, Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA

³ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences and Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA

⁴ Banner Sun Health Research Institute, Banner Health Sun City, AZ; Center for Brain/Mind Medicine, Harvard Medical School, Boston, MA, USA

⁵ Alzheimer’s Treatment Research Institute, University of Southern California, San Diego, CA, USA

⁶ Deparment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

⁷ Pentara Corporation, Millcreek, Utah, USA

⁸ Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

⁹ Departments of Radiology and Biomedical Imaging, Medicine, Psychiatry and Neurology, University of California San Francisco, San Francisco, CA, USA

¹⁰ Department of Neurology, Mayo Clinic, Rochester, MN, USA

¹¹ Butler Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA

¹² 1380 Opal Valley Street, 89052, Henderson, NV, USA

^a jcummings@cnsinnovations.com jcummings@cnsinnovations.com

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Abstract

Lecanemab (Leqembi®) is approved in the United States for the treatment of Alzheimer’s disease (AD) to be initiated in early AD (mild cognitive impairment [MCI] due to AD or mild AD dementia) with confirmed brain amyloid pathology. Appropriate Use Recommendations (AURs) are intended to help guide the introduction of new therapies into real-world clinical practice. Community dwelling patients with AD differ from those participating in clinical trials. Administration of lecanemab at clinical trial sites by individuals experienced with monoclonal antibody therapy also differs from the community clinic-based administration of lecanemab. These AURs use clinical trial data as well as research and care information regarding AD to help clinicians administer lecanemab with optimal safety and opportunity for effectiveness. Safety and efficacy of lecanemab are known only for patients like those participating in the phase 2 and phase 3 lecanemab trials, and these AURs adhere closely to the inclusion and exclusion criteria of the trials. Adverse events may occur with lecanemab including amyloid related imaging abnormalities (ARIA) and infusion reactions. Monitoring guidelines for these events are detailed in this AUR. Most ARIA with lecanemab is asymptomatic, but a few cases are serious or, very rarely, fatal. Microhemorrhages and rare macrohemorrhages may occur in patients receiving lecanemab. Anticoagulation increases the risk of hemorrhage, and the AUR recommends that patients requiring anticoagulants not receive lecanemab until more data regarding this interaction are available. Patients who are apolipoprotein E ε4 (APOE4) gene carriers, especially APOE4 homozygotes, are at higher risk for ARIA, and the AUR recommends APOE genotyping to better inform risk discussions with patients who are lecanemab candidates. Clinician and institutional preparedness are mandatory for use of lecanemab, and protocols for management of serious events should be developed and implemented. Communication between clinicians and therapy candidates or those on therapy is a key element of good clinical practice for the use of lecanemab. Patients and their care partners must understand the potential benefits, the potential harms, and the monitoring requirements for treatment with this agent. Culture-specific communication and building of trust between clinicians and patients are the foundation for successful use of lecanemab.

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Key words : Alzheimer’s disease, lecanemab, aducanumab, donanemab, appropriate use recommendations, amyloid-related imaging abnormalities (ARIA), amyloid imaging, magnetic resonance imaging (MRI), prescribing information, accelerated approval, Food and Drug Administration

Plan

Disclosure and Conflicts of Interest: JC has provided consultation to Acadia, Actinogen, Acumen, AlphaCognition, Aprinoia, AriBio, Artery, Biogen, BioVie, Cassava, Cerecin, Diadem, EIP Pharma, Eisai, GemVax, Genentech, GAP Innovations, Janssen, Jocasta, Karuna, Lilly, Lundbeck, LSP, Merck, NervGen, Novo Nordisk, Oligomerix, Optoceutics, Ono, Otsuka, PRODEO, Prothena, ReMYND, Roche, Sage Therapeutics, Signant Health, Simcere, Sunbird Bio, Suven, SynapseBio, TrueBinding,,Vaxxinity, and Wren pharmaceutical, assessment, and investment companies. JC is supported by NIGMS grant P20GM109025; NINDS grant U01NS093334; NIA grant R01AG053798; NIA grant P20AG068053; NIA grant P30AG072959; NIA grant R35AG71476; Alzheimer’s Disease Drug Discovery Foundation (ADDF); Ted and Maria Quirk Endowment; and the Joy Chambers-Grundy Endowment. LGA has provided consultation to Eli Lilly, Biogen, Two Labs, FL Dept Health, Genentech, NIH Biobank, Eli Lilly, GE Healthcare, Eisai, Roche Diagnostics, and Alnylam. LGA receives the following research support: NIA U01 AG057195, NIA R01 AG057739, NIA P30 AG010133, Alzheimer Association LEADS GENETICS 19-639372, Alzheimer Association SG-23-1061716, Roche Diagnostics RD005665, AVID Pharmaceuticals, Life Molecular Imaging. LGA has received honoraria for participating in independent data safety monitoring boards and providing educational CME lectures and programs. LGA has stock in Cassava Sciences. GDR has provided consultation to Eli Lilly, Eisai, Roche, GE Healthcare, Johnson & Johnson and Genentech pharmaceutical companies. He receives grant support from NIH, Alzheimer’s Association, American College of Radiology, Rainwater Charitable Foundation, Genentech (via the Alliance for Therapies in Neuroscience) and from Avid Radiopharmaceuticals, GE Healthcare and Life Molecular Imaging (view the New IDEAS study). AA has received honoraria for consulting; participating in independent data safety monitoring boards; providing educational lectures, programs, and materials; or serving on advisory boards for AbbVie, Acadia, Allergan, the Alzheimer’s Association, Axovant, AZ Therapies, Biogen, Eisai, Grifols, Harvard Medical School Graduate Continuing Education, JOMDD, Lundbeck, Merck, Roche/Genentech, Novo Nordisk, Qynapse, Sunovion, Suven, and Synexus. AA receives book royalties from Oxford University Press. AA receives institutional research grant/contract funding from NIA/NIH 1P30AG072980, AZ DHS CTR040636, Washington University St Louis, and Gates Ventures. His institution receives/received funding for clinical trial grants, contracts and projects from government, consortia, foundations, and companies for which he serves/served as contracted site-PI. AA served as site-PI for the EMERGE study at his previous institution. PA has received research funding from NIA, FNIH, the Alzheimer’s Association, Janssen, Lilly and Eisai, and personal fees from Biogen, Merck, Roche, Abbvie, ImmunoBrain Checkpoint, Rainbow Medical and Shionogi. SS was a site PI and co-chair of the investigator steering committee for the ENGAGE trial and he receives research support and consultancy fees from Lilly, Biogen, Avid, Eisai, Genentech, and Roche. SMG is on the Data Safety Monitoring Board for DIAN-TU and has been a consultant for Eli Lilly. SH is owner of and a full-time employee of Pentara Corporation which consults for both Biogen and Eisai and many other AD clients. DS is a director and consultant of Prothena Biosciences and serves on an Advisory Board for Eisai. MW has served on Advisory Boards for Eli Lilly, Cerecin/Accera, Roche, Alzheon, Inc., Merck Sharp & Dohme Corp., Nestle/Nestec, PCORI/PPRN, Dolby Family Ventures, National Institute on Aging (NIA), Brain Health Registry and ADNI. He serves on Editorial Boards for Alzheimer’s & Dementia, TMRI and MRI. He has provided consulting and/or acted as a speaker to Cerecin/Accera, Inc., BioClinica, Nestle/Nestec, Roche, Genentech, NIH, The Buck Institute for Research on Aging, FUJIFILM-Toyama Chemical (Japan), Garfield Weston, Baird Equity Capital, University of Southern California (USC), Cytox, and Japanese Organization for Medical Device Development, Inc. (JOMDD), Peerview Internal Medicine, Vida Ventures, Medscape, Eisai, Korean Dementia Society, China Association for Alzheimer’s Disease (CAAD, and T3D Therapeutics. He holds stock options with Alzheon, Inc., Alzeca, and Anven. RCP has served as a consultant for Roche, Inc.; Genentech, Inc.; Eisai, Inc.; Eli Lilly, Inc.; and Nestle, Inc. he receives grant support from the National Institutes of Health. SS was a site PI for CLARITY and ENGAGE and co-chair of the investigator steering committee for the ENGAGE trial and his hospital receives research support from Lilly, Biogen, Avid, Eisai, Genentech, Roche and he receives consultancy fees from Lilly, Biogen, Avid, Eisai, Genentech, Roche, Novo Nordisk, Acumen and Prothena.