Abstract
Background: Bapineuzumab is a humanized anti-amyloid-beta (Aβ) monoclonal antibodydirected 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 ofbapineuzumab in patients with the mild-to-moderate AD.
Methods: Patients (58-78 years) who completed either of two randomized, placebo-controlled, doubleblindstudies (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) inOLE (bapi SC/bapi IV); bapineuzumab (IV) in Study 201 and OLE (bapi/bapi); and placebo in Study201 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 significantdifferences for efficacy endpoints (AD Assessment Scale–cognitive subscale [ADAS-Cog], DisabilityAssessment for Dementia [DAD] and MMSE scores) between the bapi/bapi and placebo/bapigroups. Most patients (94.8%, 184/194) reported ≥1 treatment-emergent adverse events (TEAEs) inOLE. 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 withsimilar incidences between bapi/bapi and placebo/bapi groups.
Conclusion: No significant difference was seen in cognitive and functional decline between early anddelayed treatment groups. No new safety concerns emerged. ARIA-E incidence was higher in patientsfirst exposed to bapineuzumab in OLE versus previously exposed. No clear pattern of etiology contributedto death events.
Keywords:Alzheimer's disease, bapineuzumab, MRI, brain amyloid-related imaging abnormality, AD assessment scale, disabilityassessment 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: 15Issue: 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, disabilityassessment for dementia.
Abstract: Background: Bapineuzumab is a humanized anti-amyloid-beta (Aβ) monoclonal antibodydirected 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 ofbapineuzumab in patients with the mild-to-moderate AD.
Methods: Patients (58-78 years) who completed either of two randomized, placebo-controlled, doubleblindstudies (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) inOLE (bapi SC/bapi IV); bapineuzumab (IV) in Study 201 and OLE (bapi/bapi); and placebo in Study201 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 significantdifferences for efficacy endpoints (AD Assessment Scale–cognitive subscale [ADAS-Cog], DisabilityAssessment for Dementia [DAD] and MMSE scores) between the bapi/bapi and placebo/bapigroups. Most patients (94.8%, 184/194) reported ≥1 treatment-emergent adverse events (TEAEs) inOLE. 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 withsimilar incidences between bapi/bapi and placebo/bapi groups.
Conclusion: No significant difference was seen in cognitive and functional decline between early anddelayed treatment groups. No new safety concerns emerged. ARIA-E incidence was higher in patientsfirst exposed to bapineuzumab in OLE versus previously exposed. No clear pattern of etiology contributedto death events.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
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
Alzheimer's Disease Blood Tests: Advancements and the Future of Point-of-Care
The recent FDA approval of lecanemab (Leqembi), the first treatment for Alzheimer’s disease targeting early stages and mild cognitive impairment, has brought renewed hope for the therapeutic future of this devastating condition. While the exact causes and mechanisms of Alzheimer’s disease remain obscure, there is an urgent consensus on the ...read more
Drug Discovery and Possible Therapeutic Developments in Neurological Disorders Alzheimer’s Disease and Tauopathy
A critical appraisal Alzheimer's disease (AD) is a devastating mental illness in society and the etiology and pathogenesis of AD are still poorly understood. One of the key hallmark pathological proteins of AD is tau, where the pathophysiology and the functional relationships between hyperphosphorylation of tau and synaptic damage in ...read more
Early nutritional intervention and physical activity in the prevention of Alzheimer's disease and other dementias
The aim is to broaden the knowledge about the impact of the consumption of food ingredients, diet ingredients, methods of processing of food raw materials as well as the impact of composing of diets on the possibility of preventing Alzheimer's disease and other types of dementia at each stage of ...read more
Related Journals
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Diabetes Reviews
Current Neuropharmacology
Current Neurovascular Research
Central Nervous System Agents in Medicinal Chemistry
Current Respiratory Medicine Reviews
Current Pediatric Reviews
Infectious Disorders - Drug Targets
Endocrine, Metabolic & Immune Disorders - Drug Targets
Current Stem Cell Research & Therapy
Related Books
Gut Microbiota and their Impact on Disease Pathways and Interventions
Organ-specific Parasites in Cattle
Infections and Male Infertility: General Pathophysiology, Diagnosis, and Treatment
Advancements in Cancer Research: Exploring Diagnostics and Therapeutic Breakthroughs
Common Ear Diseases in Dogs: Diagnosis and Management
Metabolic Syndrome: A Comprehensive Update with New Insights
Vector Borne Diseases: Current Trends and Public Health Perspectives
Parasitic Diseases of Goats
Concise Handbook of Epidemiology (Second Edition)
Human Papillomavirus Vaccination and Screening in the Elimination of HPV-Associated Cancers: Evidence-Based Randomized Trials
90
- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
- Relaxin Receptors - New Drug Targets for Multiple Disease States
Current Drug TargetsSelenoproteins and their Role in Oxidative Stress and Inflammation
Current Chemical Biology Recent Patents on Cardiovascular Stem Cells
Recent Patents on Cardiovascular Drug Discovery Cardiac Metabolism in Diabetes Mellitus
Current Pharmaceutical Design The PKB/AKT Pathway in Cancer
Current Pharmaceutical DesignPolyamines and Related Nitrogen Compounds in the Chemotherapy of Neglected Diseases Caused by Kinetoplastids
Current Topics in Medicinal ChemistryPatent Selections:
Recent Patents on Inflammation & Allergy Drug DiscoveryClinical Approach to Diabetic Cardiomyopathy: A Review of Human Studies
Current Medicinal ChemistryDetermination of Stimulants and Diuretics in Dietary Supplements for Weight Loss and Physical Fitness by Ion-pair Chromatography and Pulsed Amperometric Detection (PAD)
Current Analytical ChemistrymicroRNA-133: Expression, Function and Therapeutic Potential in Muscle Diseases and Cancer
Current Drug TargetsAMPK As A Target in Rare Diseases
Current Drug TargetsA Comprehensive Review on Ethnomedicinal, Pharmacological and Phytochemical Basis of Anticancer Medicinal Plants of Pakistan
Current Cancer Drug Targets Fatty Liver and Ischemia/Reperfusion: Are there Drugs Able to Mitigate Injury?
Current Medicinal Chemistry Diagnostic Approach to Mitochondrial Disorders: the Need for a Reliable Biomarker
Current Molecular MedicineRole of Methylglyoxal in Diabetic Cardiovascular and Kidney Diseases: Insights from Basic Science for Application into Clinical Practice
Current Pharmaceutical Design Targeting Antioxidants to Mitochondria: A Potential New Therapeutic Strategy for Cardiovascular Diseases
Current Pharmaceutical Design GLP - 1 Analogs: Newer Molecules, Newer Uses
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) PDE5 Inhibitors in Non-Urological Conditions
Current Pharmaceutical DesignThe Proteasome in Health and Disease
Current Pharmaceutical DesignIncremental Value of Two Dimensional Speckle Tracking Echocardiography in the Functional Assessment and Characterization of Subclinical Left Ventricular Dysfunction
Current Cardiology Reviews
[8]ページ先頭