Gantenerumab

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.