Aducanumab: Appropriate Use Recommendations Update DOI Creative Commons
Jeffrey L. Cummings, Gil D. Rabinovici, Alireza Atri

et al.

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2022, Volume and Issue: unknown

Published: Jan. 1, 2022

Aducanumab (Aduhelm) is approved in the United States for treatment of patients with mild cognitive impairment due to Alzheimer's disease or AD dementia. Appropriate Use Recommendations (AURs) have been published and helped guide best practices use aducanumab. As real-world has occurred more information accrued, AURs require refinement. We update better inform appropriate patient selection improve shared decision-making, safety monitoring, risk mitigation treated patients. Based on evolving experience we emphasize importance detecting past medical conditions that may predispose amyloid related imaging abnormalities (ARIA) increase likelihood ARIA complications including autoimmune inflammatory conditions, seizures, disorders associated extensive white matter pathology. The apolipoprotein E ε4 (APOE4) genotype strongly exhibits a gene dose effect. recommend clinicians perform APOE genotyping care decisions, discussions regarding risk, clinician vigilance concerning ARIA. most occurs during titration period aducanumab, suggest performing MRI before 5th, 7th, 9th, 12th infusions detection. Uncommonly, be recurrent serious; additional parameters discontinuation taking these observations into account. It important continue learn from aducanumab will evolve as new becomes available. This AUR does not address efficacy, price, insurance coverage provided assist establish

Language: Английский

Lecanemab in Early Alzheimer’s Disease DOI Open Access
Christopher H. van Dyck,

Chad J. Swanson,

Paul Aisen

et al.

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 388(1), P. 9 - 21

Published: Nov. 30, 2022

The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathologic processes in Alzheimer's disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ protofibrils, is being tested persons early

Language: Английский

Citations

2777
Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease DOI Creative Commons
Samantha Budd Haeberlein,

Paul Aisen,

Frederik Barkhof

et al.

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2022, Volume and Issue: unknown

Published: Jan. 1, 2022

Alzheimer's disease is a progressive, irreversible, and fatal for which accumulation of amyloid beta thought to play key role in pathogenesis. Aducanumab human monoclonal antibody directed against aggregated soluble insoluble forms beta.We evaluated the efficacy safety aducanumab early disease.EMERGE ENGAGE were two randomized, double-blind, placebo-controlled, global, phase 3 studies patients with disease.These involved 348 sites 20 countries.Participants included 1638 (EMERGE) 1647 (ENGAGE) (aged 50-85 years, confirmed pathology) who met clinical criteria mild cognitive impairment due or dementia, 1812 (55.2%) completed study.Participants randomly assigned 1:1:1 receive low dose (3 6 mg/kg target dose), high (10 placebo via IV infusion once every 4 weeks over 76 weeks.The primary outcome measure was change from baseline week 78 on Clinical Dementia Rating Sum Boxes (CDR-SB), an integrated scale that assesses both function cognition. Other measures assessments; secondary tertiary outcomes assessed cognition, function, behavior; biomarker endpoints.EMERGE halted based futility analysis data pooled first approximately 50% enrolled patients; subsequent analyses larger set collected up declaration followed prespecified statistical analyses. The endpoint EMERGE (difference -0.39 high-dose vs [95% CI, -0.69 -0.09; P=.012; 22% decrease]) but not 0.03, -0.26 0.33; P=.833; 2% increase]). Results substudies engagement dose-dependent reduction markers pathophysiology. most common adverse event amyloid-related imaging abnormalities-edema.Data demonstrated statistically significant across all four endpoints. did meet its A dose- time-dependent pathophysiological observed trials.

Language: Английский

Citations

801
Alzheimer's disease drug development pipeline: 2022 DOI Creative Commons
Jeffrey L. Cummings, Garam Lee,

Pouyan Nahed

et al.

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2022, Volume and Issue: 8(1)

Published: Jan. 1, 2022

Alzheimer's disease (AD) represents a global health crisis. Treatments are needed to prevent, delay the onset, slow progression, improve cognition, and reduce behavioral disturbances of AD. We review current clinical trials drugs in development for treatment

Language: Английский

Citations

535
The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics DOI
Eric Karran, Bart De Strooper

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(4), P. 306 - 318

Published: Feb. 17, 2022

Language: Английский

Citations

487
Lecanemab: Appropriate Use Recommendations DOI

J Cummings,

L Apostolova,

G D Rabinovici

et al.

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

Language: Английский

Citations

371
Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future DOI Creative Commons
Yun Zhang, Huaqiu Chen, Ran Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 30, 2023

Abstract Amyloid β protein (Aβ) is the main component of neuritic plaques in Alzheimer’s disease (AD), and its accumulation has been considered as molecular driver pathogenesis progression. Aβ prime target for development AD therapy. However, repeated failures Aβ-targeted clinical trials have cast considerable doubt on amyloid cascade hypothesis whether drug followed correct course. recent successes targeted assuaged those doubts. In this review, we discussed evolution over last 30 years summarized application diagnosis modification. particular, extensively pitfalls, promises important unanswered questions regarding current anti-Aβ therapy, well strategies further study more feasible approaches optimization prevention treatment.

Language: Английский

Citations

364
The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease DOI Creative Commons
Oskar Hansson, Rebecca M. Edelmayer, Adam L. Boxer

et al.

Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 18(12), P. 2669 - 2686

Published: July 31, 2022

Abstract Blood‐based markers (BBMs) have recently shown promise to revolutionize the diagnostic and prognostic work‐up of Alzheimer's disease (AD), as well improve design interventional trials. Here we discuss in detail further research needed be performed before widespread use BBMs. We already now recommend BBMs (pre‐)screeners identify individuals likely AD pathological changes for inclusion trials evaluating disease‐modifying therapies, provided status is confirmed with positron emission tomography (PET) or cerebrospinal fluid (CSF) testing. also encourage studying longitudinal BBM ongoing future However, should not yet used primary endpoints pivotal Further, cautiously start using specialized memory clinics part patients cognitive symptoms results whenever possible CSF PET. Additional data are stand‐alone markers, considering care.

Language: Английский

Citations

362
The probabilistic model of Alzheimer disease: the amyloid hypothesis revised DOI
Giovanni B. Frisoni, Daniele Altomare, Dietmar Rudolf Thal

et al.

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 23(1), P. 53 - 66

Published: Nov. 23, 2021

Language: Английский

Citations

328
Alzheimer's disease drug development pipeline: 2023 DOI Creative Commons
Jeffrey L. Cummings, Yadi Zhou, Garam Lee

et al.

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2023, Volume and Issue: 9(2)

Published: April 1, 2023

Drugs that prevent the onset, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed.

Language: Английский

Citations

325
Antibodies to watch in 2022 DOI Creative Commons
Hélène Kaplon, Alicia M. Chenoweth, Silvia Crescioli

et al.

mAbs, Journal Year: 2022, Volume and Issue: 14(1)

Published: Jan. 14, 2022

In this 13th annual installment of the ‘Antibodies to Watch’ article series, we discuss key events in commercial antibody therapeutics development that occurred 2021 and forecast might occur 2022. Regulatory review target SARS-CoV-2 coronavirus proceeded at an unprecedented pace 2021, resulting both emergency use authorizations full approvals for sotrovimab, regdanvimab, REGEN-COV2, as well others, numerous countries. As November 1, a total 11 had been granted first either United States or European Union (evinacumab, dostarlimab loncastuximab tesirine, amivantamab, aducanumab, tralokinumab, anifrolumab, bimekizumab, tisotumab vedotin, REGEN-COV2). The global seven products, however, were elsewhere, including Japan (pabinafusp alfa), China (disitamab penpulimab, zimberelimab), Australia (sotrovimab, REGEN-COV2), Republic Korea (regdanvimab). Globally, least 27 novel are undergoing by regulatory agencies. First actions Food Drug Administration on biologics license applications faricimab, sutimlimab, tebentafusp, relatlimab, sintilimab, ublituximab tezepelumab expected quarter Finally, our data show that, with antibodies COVID-19 excluded, late-stage clinical pipeline grew over 30% past year. Of those development, marketing 22 may end

Language: Английский

Citations

303