Genentech to Discontinue Phase III CREAD 1 and 2 Clinical Studies of Crenezumab in Early Alzheimer’s Disease (AD)

Genentech announced the decision to discontinue CREAD 1 and CREAD 2 (BN29552 and BN29553) Phase III studies of the investigational anti-beta-amyloid molecule crenezumab in people with early (prodromal to mild) sporadic Alzheimer’s disease (AD). The decision was based on the results of a pre-planned interim analysis assessing the safety and efficacy of crenezumab conducted by the Independent Data Monitoring Committee, which indicated that crenezumab was unlikely to meet the primary endpoint of change from baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score. No safety signals for crenezumab were observed in this analysis, and the overall safety profile was similar to that seen in previous trials.

Data from the CREAD 1 and 2 studies will be shared with the scientific community at an upcoming medical congress. Findings from the trials will inform future research programs, approaches and clinical trial designs.

“While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of Alzheimer’s disease,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We gratefully acknowledge the participants in the CREAD trials and the efforts of everyone involved in this important program. We remain dedicated to the Alzheimer’s community and will continue our Phase III GRADUATE trials with gantenerumab and the Phase II TAURIEL trial with the anti-tau molecule RG6100, as well as our imaging and fluid-based diagnostic solutions.”

CREAD 1 and 2 are two-year global, randomized, double-blind, placebo-controlled, parallel-group Phase III studies testing the efficacy and safety of crenezumab in 1,500 people worldwide with early AD with confirmed evidence of cerebral beta amyloid pathology (CSF or amyloid PET). These studies use doses four times higher than that studied in the Phase II trials. CREAD 1 was initiated in early 2016 and CREAD 2 in mid-2017.

Crenezumab continues to be studied in the Alzheimer’s Prevention Initiative (API) trial investigating a different study population from that of the CREAD program, namely cognitively healthy individuals in Colombia with an autosomal dominant mutation who are at risk of developing familial AD (fAD). The five-year study is in collaboration with the Banner Institute and is also funded by the National Institute on Aging.