The phase 3 studies, CREAD 1 (NCT02670083) and CREAD 2 (NCT03114657), of crenezumab (Genetech, South San Francisco, CA), an investigational monoclonal antibody to amyloid ß (Aß) being studied for treatment of individuals with early (prodromal to mild) sporadic Alzheimer’s disease (AD). Crenezumab was designed to preferentially bind to and promote removal of neurotoxic oligomers of Aß. Data from the studies will be shared at an upcoming medical congress and findings from the trials will inform future research programs, approaches, and clinical trial designs.
The decision to discontinue the studies was based on results of an interim analysis by the Independent Data Monitoring Committee showing crenezumab was unlikely to meet the primary endpoint of change from baseline using the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score.
Despite discontinuation of this trial, Genetech noted that they remain committed to developing treatments for people with AD. A study of crenezumab for prevention of familial AD, the Alzheimer’s Prevention Initiative will be continued. Studies of another monoclonal antibody, gantenerumab, and the antitau molecule RG6100, both also produced by Genetech will also continue.
“While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of AD,” said Sandra Horning, MD, chief medical officer and head of global product development at Genentech. “We remain dedicated to the Alzheimer’s community and will continue our phase 3 GRADUATE (NCT03444870, NCT03443973) trials with gantenerumab and the phase 2 TAURIEL (NCT03289143) trial with the anti-tau molecule RG6100.”
Lee I. Kubersky, MD
Britany Klenofsky, MD, and Huma U. Sheikh, MD
Leeann B. Burton, MD, and Amanda C. Guidon, MD