Crenezumab

Analyst Outlook

Despite questionable signs of cognitive efficacy in crenezumab’s (Roche) ABBY Phase II study in mild to moderate Alzheimer’s disease, Roche was encouraged to launch a Phase III study following the positive outcome of Biogen’s PRIME trial of aducanumab. While the PRIME study might have rejuvenated hope in the amyloid-beta hypothesis to treat the early stages of Alzheimer’s disease, Roche’s decision to progress crenezumab into late-stage trials is certainly speculative. Nevertheless, crenezumab has hypothetical benefits that may allow for higher doses and greater tolerability, meaning the drug has a comparable likelihood of success to aducanumab in Phase III trials for early-
stage Alzheimer’s disease.

Drug Overview

Crenezumab (Roche), created by AC Immune’s SupraAntigen technology platform, is a fully humanized immunoglobulin G4 monoclonal antibody that recognizes amyloid-beta’s mid-section. It binds to multiple forms of amyloid-beta, preventing any further plaque formation, which is a key pathology in Alzheimer’s disease. Crenezumab also promotes microglia-induced phagocytosis resulting in amyloid-beta clearance, while avoiding the activation of microglia-mediated inflammatory responses. Thus, any unwanted inflammatory side effects such as vasogenic edema are limited. This feature enables crenezumab to be dosed higher than other amyloid antibodies.

Crenezumab has completed Phase II trials in mild to moderate Alzheimer’s disease and in patients at risk of familial Alzheimer’s disease due to genetic susceptibility. In July 2015, Roche announced that crenezumab will move into Phase III clinical development in prodromal to mild Alzheimer’s disease.