Overview
Alzheimer's disease (AD) is the most common cause of dementia in elderly patients, with classical histopathological hallmarks including extracellular amyloid-beta (Aβ) plaques and intraneuronal neurofibrillary tangles (NFTs). As the classical view of AD pathology posits that Aβ accumulation triggers tau hyperphosphorylation and aggregation to form NFTs and cause neurodegeneration, large efforts have gone into developing treatments to reduce Aβ aggregation and remove Aβ plaques. These treatments include the related antibodies aducanumab, which has been granted accelerated FDA approval, along with bapineuzumab, crenezumab, donanemab, lecanemab, and solanezumab, which are at varying stages of clinical development. Despite the clear association of Aβ aggregation with AD, treatments aimed at preventing Aβ aggregation or removing pre-existing Aβ plaques have shown little to no clinical benefit thus far and remain controversial. Gantenerumab is a fully human IgG1κ monoclonal antibody derived from the MorphoSys HuCAL®-Fab1 phage display library and subsequently optimized by in vitro CDR cassette exchange. Gantenerumab binds to a unique Aβ epitope compared to other anti-Aβ antibodies and preferentially recognizes Aβ oligomers and fibrils over monomers.
Indication
No indication information available.
Associated Conditions
No associated conditions information available.
Research Report
Gantenerumab (DB12034): A Comprehensive Clinical and Scientific Monograph on a Pivotal Case Study in Alzheimer's Drug Development
Executive Summary
Gantenerumab (DB12034) represents one of the most significant and instructive case studies in the modern era of Alzheimer's disease (AD) drug development. Developed by Hoffmann-La Roche, it was engineered as a first-in-class, fully human IgG1 monoclonal antibody targeting aggregated forms of beta-amyloid (Aβ), the pathological hallmark protein central to the amyloid cascade hypothesis. The therapeutic rationale was straightforward: by binding to and clearing Aβ plaques from the brain, Gantenerumab was expected to modify the disease course and slow cognitive decline. Its development incorporated strategic innovations, including a fully human design to minimize immunogenicity and a subcutaneous formulation to enhance patient convenience and accessibility.
Throughout its extensive clinical program, Gantenerumab consistently demonstrated target engagement, proving its ability to reduce the burden of cerebral Aβ plaques in a dose-dependent manner. This biological activity supported its advancement into large-scale, pivotal Phase 3 trials. However, the comprehensive GRADUATE I and II studies, which enrolled nearly 2,000 individuals with early, sporadic AD, ultimately delivered a definitive negative result. Despite statistically significant reductions in amyloid biomarkers, the treatment failed to produce a statistically significant slowing of clinical decline. The magnitude of amyloid clearance was ultimately deemed insufficient to alter the disease's symptomatic progression, leading to the discontinuation of the development program for sporadic AD in late 2022.
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2024/05/22 | Phase 2 | Terminated | |||
2022/02/25 | Phase 3 | Terminated | |||
2020/11/10 | Phase 2 | Completed | |||
2020/10/19 | Phase 2 | Terminated | |||
2020/05/05 | Phase 3 | Terminated | |||
2020/04/09 | Phase 3 | Terminated | |||
2018/02/23 | Phase 3 | Terminated | |||
2018/02/23 | Phase 3 | Terminated | |||
2017/08/02 | Phase 1 | Completed | |||
2016/08/29 | Phase 1 | Completed |
FDA Drug Approvals
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| No FDA approvals found for this drug. | |||||
EMA Drug Approvals
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| No EMA approvals found for this drug. | |||
HSA Drug Approvals
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| No HSA approvals found for this drug. | |||||
NMPA Drug Approvals
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| No NMPA approvals found for this drug. | |||||
PPB Drug Approvals
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| No PPB approvals found for this drug. | |||||
TGA Drug Approvals
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| No TGA approvals found for this drug. | |||||
Health Canada Drug Approvals
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| No Health Canada approvals found for this drug. | |||||
CIMA AEMPS Drug Approvals
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| No CIMA AEMPS (Spain) approvals found for this drug. | |||||
Philippines FDA Drug Approvals
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| No Philippines FDA approvals found for this drug. | |||||
Saudi SFDA Drug Approvals
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| No Saudi SFDA approvals found for this drug. | |||||
Malaysia NPRA Drug Approvals
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| No Malaysia NPRA approvals found for this drug. | |||||
UK EMC Drug Information
Medicine Name | MA Holder | MA Number | Pharmaceutical Form | Active Ingredient | Authorization Date |
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| No UK EMC drug information found for this drug. | |||||
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