Long-Term Follow Up of Patients with Mild-to-Moderate Alzheimer’s Disease Treated with Bapineuzumab in a Phase III, Open-Label, Extension Study

Salloway, Stephen; Sperling, Reisa A.; Fox, Nick C.; Sabbagh, Marwan N.; Honig, Lawrence S.; Porsteinsson, Anton P.; Rofael, Hany; Ketter, Nzeera; Wang, Daniel; Liu, Enchi; Carr, Stephen R.; Black, Ronald S.; Brashear, H. Robert

doi:10.3233/jad-171157

Cited by 17 publications

(8 citation statements)

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“…Two hundred eighty-four relevant studies were screened and assessed for eligibility. After applying inclusion and exclusion criteria (eFigure in the Supplement), 22 publications of RCTs (evidence level 1B), 11 secondary analyses of RCT data (evidence level 2B), and 1 clinical case report (evidence level 4), including in total 15 508 adult patients (7025 men [45.3%] and 8483 women [54.7%]; mean [SD] age, 69.6 [8.3] years), were selected for inclusion. Table 2 summarizes findings of the included RCTs, whereas eTable 1 in the Supplement reports findings from secondary analyses of RCT data and the case report.…”

Section: Resultsmentioning

confidence: 99%

“…Amyloid-Related Imaging Abnormalities and β-Amyloid-Targeting Antibodies bapineuzumab) in a phase 1 study 20 revealed instead a better safety profile (Table 2). Due to growing awareness about the need for expertise in ARIA evaluation, during the conduction of phase 3 studies, [21][22][23][24] reporting of safety MRI scans was gradually transferred from local responsibility to central readers (safety read). In a central MRI second review (final read) of the more than 2000 patients who had completed their participation in phase 3 studies, 39 ARIA-E was detected in 13% of patients receiving active treatment.…”

Section: Clinical Review and Education Reviewmentioning

confidence: 99%

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Amyloid-Related Imaging Abnormalities and β-Amyloid–Targeting Antibodies

et al. 2022

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IMPORTANCEAfter more than a decade of research and development of clinical trials testing anti-β-amyloid monoclonal antibodies (mAbs), extensive experience has been gained regarding the effects of these treatments in patients with Alzheimer disease (AD). On the verge of an expected large-scale introduction in the clinical setting after the recent US Food and Drug Administration approval of aducanumab, shared knowledge regarding amyloid-related imaging abnormalities (ARIAs) is of paramount importance.OBJECTIVE To summarize available evidence on ARIAs from randomized clinical trials (RCTs) testing anti-β-amyloid mAbs in patients with AD and to provide a comprehensive update about risk factors, clinical correlates, and implications for withholding and reinitiating treatment.EVIDENCE REVIEW In this systematic review, a literature search of MEDLINE/PubMed, Embase, and Cochrane Library and a search of ClinicalTrials.gov were conducted through September 15, 2021. Publications describing RCTs, secondary analyses of RCT data, and case reports of ARIAs were included. Strengths of clinical data were graded according to the Oxford Centre for Evidence-Based Medicine.FINDINGS Twenty-two RCTs, 11 secondary analyses of RCTs, and 1 case report, including in total 15 508 adult patients (8483 women [54.7%]; mean [SD] age, 69.6 [8.3] years) were selected for inclusion. Signal alterations that included parenchymal edema and sulcal effusion leading to transient hyperintensities on fluid-attenuated inversion recovery and T2-weighted sequences were termed ARIA-E, whereas those consisting of hemosiderin deposits, including parenchymal microhemorrhages and leptomeningeal superficial siderosis, were termed ARIA-H. Apolipoprotein E (ApoE) ε4 genotype was the main risk factor for both ARIA types; ARIA-E incidence was further associated with treatment dose, affecting the 55% of ApoE ε4 carriers in the high-dose aducanumab treatment group. Both ARIA types manifested early during study course, and symptomatic cases accounted for the 6.1% to 39.3% of ARIA-E cases at higher treatment doses across RCTs, whereas ARIA-H cases were generally asymptomatic. Most ARIA-E cases resolved with treatment withholding, although corticosteroid administration was required anecdotally. ARIA-E recurrence after dose reinitiation or adjustment varied from 13.8% to 25.6% across RCTs.CONCLUSIONS AND RELEVANCE Evidence suggests that ARIAs are frequent, mostly asymptomatic collateral events of amyloid-modifying therapies, highlighting the need for standardized clinical and neuroradiological management protocols in real-world clinical settings.

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Section: Resultsmentioning

confidence: 99%

Section: Clinical Review and Education Reviewmentioning

confidence: 99%

Amyloid-Related Imaging Abnormalities and β-Amyloid–Targeting Antibodies

et al. 2022

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“…Solanezumab ( Honig et al, 2018 ; Liu-Seifert, et al, 2018 ), bapineuzumab ( Arai et al, 2016 ; Brody et al, 2016 ; Ivanoiu et al, 2016 ; Vandenberghe et al, 2016 ; Salloway et al, 2018a ; Salloway et al, 2018b ), BAN2401 ( Logovinsky et al, 2016 ), and gantenerumab ( Ostrowitzki et al, 2017 ) are monoclonal anti-Aβ antibodies. In addition to bapineuzumab phase 1 trial results of increasing plasma concentrations of β-amyloid1-40 in patients ( Arai et al, 2016 ), all anti-Aβ antibodies failed in therapeutic efficiency, discouraging further studies.…”

Section: Potential Targets For Drug Designmentioning

confidence: 99%

Advances in Alzheimer’s disease’s pharmacological treatment

et al. 2023

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Alzheimer’s disease (AD) is the most common type of dementia in the elderly. Several hypotheses emerged from AD pathophysiological mechanisms. However, no neuronal protective or regenerative drug is available nowadays. Researchers still work in drug development and are finding new molecular targets to treat AD. Therefore, this study aimed to summarize main advances in AD pharmacological therapy. Clinical trials registered in the National Library of Medicine database were selected and analyzed accordingly to molecular targets, therapeutic effects, and safety profile. The most common outcome was the lack of efficacy. Only seven trials concluded that tested drugs were safe and induced any kind of therapeutic improvement. Three works showed therapeutic effects followed by toxicity. In addition to aducanumab recent FDA approval, antibodies against amyloid-β (Aβ) showed no noteworthy results. 5-HT6 antagonists, tau inhibitors and nicotinic agonists’ data were discouraging. However, anti-Aβ vaccine, BACE inhibitor and anti-neuroinflammation drugs showed promising results.

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“…The first studied candidate monoclonal antibody was bapineuzumab, which targets the Aβ N-terminus and possesses a higher affinity for deposited amyloid plaques than soluble Aβ monomers (116,117). However, multiple studies and a meta-analysis conducted by Abushouk et al assessing the potential use of bapineuzumab in the treatment of AD, reported significant association with severe adverse events and no enhancement of cognitive decline, and therefore concluded that bapineuzumab is not recommended for use in the treatment of AD and clinical trials have since then been discontinued (117)(118)(119)(120)(121)(122)(123).…”

Section: Clinical Trialsmentioning

confidence: 99%

Immunotherapies for Neurodegenerative Diseases

et al. 2021

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The current treatments for neurodegenerative diseases are mostly symptomatic without affecting the underlying cause of disease. Emerging evidence supports a potential role for immunotherapy in the management of disease progression. Numerous reports raise the exciting prospect that either the immune system or its derivative components could be harnessed to fight the misfolded and aggregated proteins that accumulate in several neurodegenerative diseases. Passive and active vaccinations using monoclonal antibodies and specific antigens that induce adaptive immune responses are currently under evaluation for their potential use in the development of immunotherapies. In this review, we aim to shed light on prominent immunotherapeutic strategies being developed to fight neuroinflammation-induced neurodegeneration, with a focus on innovative immunotherapies such as vaccination therapy.

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Long-Term Follow Up of Patients with Mild-to-Moderate Alzheimer’s Disease Treated with Bapineuzumab in a Phase III, Open-Label, Extension Study

Abstract: Infusion of bapineuzumab 0.5 or 1.0 mg/kg every 13 weeks for up to 3 years was generally well tolerated, with a safety and tolerability profile similar to that in previous studies.

Cited by 17 publications

References 23 publications

Amyloid-Related Imaging Abnormalities and β-Amyloid–Targeting Antibodies

Amyloid-Related Imaging Abnormalities and β-Amyloid–Targeting Antibodies

Advances in Alzheimer’s disease’s pharmacological treatment

Immunotherapies for Neurodegenerative Diseases

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