TrialWatch: Genentech Halts Phase 3 Crenezumab Trial

Feb 2, 2019 | Alzheimer, Alzheimer's Disease Trial, Challenging Results, Genentech

Alzheimer Trial Failure

Patricia Inacio writing for Alzheimer’s Today reports that Genentech (Roche) has halted two Phase 3 trials (CREAD 1 and CREAD 2) that were evaluating crenezumab as a therapy for early Alzheimer’s disease.  Genentech announced that the decision was based on an interim analysis by an independent data monitoring committee that ruled that crenezumab was unlikely to meet its primary goal of halting dementia progression as measured by the Clinical Dementia Rating-Sum of Boxes Score. Crenezumab is a fully humanized monoclonal antibody against human 1-40 and 1-42 Beta amyloid, which is being investigated as a treatment of Alzheimer’s disease. Crenezumab is highly homologous to solanezumab, another monoclonal antibody targeting amyloid-β peptides.  Crenezumab was developed by Ruth Greferath and Claude Nicolau, at the Swiss-based biopharmaceutical company AC Immune, which focuses on developing targeted therapeutics for misfolded proteins that cause neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease.  AC Immune was founded in 2003 by current CEO Andrea Pfeifer, Ph.D.  and funded primarily by German billionaire Dietmar Hopp.  In 2016, AC Immune filed for an IPO valuing the company at $700 million and subsequently sold 6.9 million shares for net proceeds of $68.73 million.

To develop crenezumab, AC Immune utilized its SupraAntigen technology, which involves injecting mice with liposomes that contain several hundred peptide mimics of antigens in order to generate a multitude of antibodies, from which the ones with best specificity are selected. It is believed that crenezumab works by causing beta amyloid proteins to transition from an insoluble to a soluble form, inhibiting aggregation and promoting disaggregation of existing plaques.

Crenezumab was licensed to Genentech, Inc. in 2006. Genentech is fully responsible for the clinical development, manufacturing, and commercialization of crenezumab.  In July 2015, Genentech announced it was moving crenezumab into a phase III study, known as CREAD, to evaluate the effects of crenezumab in patients with prodromal-to-mild Alzheimer’s Disease. This study aims to enroll 750 individuals between the ages of 50 and 85 at 233 international sites. The primary outcome measure for this trial is change in clinical dementia rating, with secondary outcomes of changes in cognition, quality of life, and time to clinically evident decline, among others. The study was expected to conclude in 2021 but Roche has withdrawn its support in the middle of Phase III due to the initial assessment.


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