Abstract
Background: Bapineuzumab is a humanized anti-amyloid-beta (Aβ) monoclonal antibody directed at lowering the cerebral Aβ deposit in Alzheimer’s disease (AD).
Objective:This phase 2, open-label extension (OLE) study evaluated long-term safety and efficacy of bapineuzumab in patients with the mild-to-moderate AD.
Methods: Patients (58-78 years) who completed either of two randomized, placebo-controlled, doubleblind studies (subcutaneous [SC] single-dose-escalation, or intravenous (IV) multiple-ascending-dose)) entered the OLE. Three groups were assessed: bapineuzumab or placebo SC, and bapineuzumab (IV) in OLE (bapi SC/bapi IV); bapineuzumab (IV) in Study 201 and OLE (bapi/bapi); and placebo in Study 201 and bapineuzumab IV in OLE (placebo/bapi).
Results: Of 194 patients enrolled, 158 withdrew from OLE; primarily due to withdrawal by subject (n=85) and AE (n=30). Mean (SD) bapineuzumab exposure was 2.9 (1.90) years. There were no significant differences for efficacy endpoints (AD Assessment Scale–cognitive subscale [ADAS-Cog], Disability Assessment for Dementia [DAD] and MMSE scores) between the bapi/bapi and placebo/bapi groups. Most patients (94.8%, 184/194) reported ≥1 treatment-emergent adverse events (TEAEs) in OLE. Amyloid-related imaging abnormalities with effusion or edema (ARIA-E) occurred in 22 (11.3%) patients. The most common TEAEs (>20% patients) were fall, agitation and urinary tract infection with similar incidences between bapi/bapi and placebo/bapi groups.
Conclusion: No significant difference was seen in cognitive and functional decline between early and delayed treatment groups. No new safety concerns emerged. ARIA-E incidence was higher in patients first exposed to bapineuzumab in OLE versus previously exposed. No clear pattern of etiology contributed to death events.
Keywords: Alzheimer's disease, bapineuzumab, MRI, brain amyloid-related imaging abnormality, AD assessment scale, disability assessment for dementia.
Current Alzheimer Research
Title:Long-Term Safety and Efficacy of Bapineuzumab in Patients with Mild-to-Moderate Alzheimer’s Disease: A Phase 2, Open-Label Extension Study
Volume: 15 Issue: 13
Author(s): Stephen Salloway, Gad A. Marshall, Ming Lu and H. Robert Brashear*
Affiliation:
- Janssen Research & Development, Pennington, NJ 08534,United States
Keywords: Alzheimer's disease, bapineuzumab, MRI, brain amyloid-related imaging abnormality, AD assessment scale, disability assessment for dementia.
Abstract: Background: Bapineuzumab is a humanized anti-amyloid-beta (Aβ) monoclonal antibody directed at lowering the cerebral Aβ deposit in Alzheimer’s disease (AD).
Objective:This phase 2, open-label extension (OLE) study evaluated long-term safety and efficacy of bapineuzumab in patients with the mild-to-moderate AD.
Methods: Patients (58-78 years) who completed either of two randomized, placebo-controlled, doubleblind studies (subcutaneous [SC] single-dose-escalation, or intravenous (IV) multiple-ascending-dose)) entered the OLE. Three groups were assessed: bapineuzumab or placebo SC, and bapineuzumab (IV) in OLE (bapi SC/bapi IV); bapineuzumab (IV) in Study 201 and OLE (bapi/bapi); and placebo in Study 201 and bapineuzumab IV in OLE (placebo/bapi).
Results: Of 194 patients enrolled, 158 withdrew from OLE; primarily due to withdrawal by subject (n=85) and AE (n=30). Mean (SD) bapineuzumab exposure was 2.9 (1.90) years. There were no significant differences for efficacy endpoints (AD Assessment Scale–cognitive subscale [ADAS-Cog], Disability Assessment for Dementia [DAD] and MMSE scores) between the bapi/bapi and placebo/bapi groups. Most patients (94.8%, 184/194) reported ≥1 treatment-emergent adverse events (TEAEs) in OLE. Amyloid-related imaging abnormalities with effusion or edema (ARIA-E) occurred in 22 (11.3%) patients. The most common TEAEs (>20% patients) were fall, agitation and urinary tract infection with similar incidences between bapi/bapi and placebo/bapi groups.
Conclusion: No significant difference was seen in cognitive and functional decline between early and delayed treatment groups. No new safety concerns emerged. ARIA-E incidence was higher in patients first exposed to bapineuzumab in OLE versus previously exposed. No clear pattern of etiology contributed to death events.
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Cite this article as:
Salloway Stephen , Marshall A. Gad , Lu Ming and Brashear Robert H.*, Long-Term Safety and Efficacy of Bapineuzumab in Patients with Mild-to-Moderate Alzheimer’s Disease: A Phase 2, Open-Label Extension Study, Current Alzheimer Research 2018; 15 (13) . https://dx.doi.org/10.2174/1567205015666180821114813
DOI https://dx.doi.org/10.2174/1567205015666180821114813 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
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