Basel and Lausanne, Switzerland—Roche announced today the decision to discontinue CREAD 1 and CREAD 2 Phase 3 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.
Crenezumab is an investigational, monoclonal antibody designed to preferentially bind to and promote removal of neurotoxic oligomers, a form of beta-amyloid. Crenezumab has an antibody backbone (IgG4) designed to minimize the inflammatory response in the brain, which may result in a lower risk of certain MRI (magnetic resonance imaging) abnormalities known as ARIA (amyloid-related imaging abnormalities). Crenezumab is being developed by Roche and was discovered by Swiss biotechnology company AC Immune SA.
Data from the CREAD 1 and 2 studies will be shared with the scientific community at an upcoming medical congress. Roche notes that findings from the trials will inform future research programs, approaches and clinical trial designs. AC Immune says it looks forward to receiving and reviewing the data in detail and sharing it as appropriate, following peer review.
“While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of Alzheimer’s disease,” said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development at Roche. “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 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 3 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 a landmark trial of cognitively healthy individuals in Colombia with an autosomal dominant mutation who are at risk of developing familial AD (fAD), under the Alzheimer's Prevention Initiative (API), which began in 2013. This study will determine if treating people carrying this mutation with crenezumab prior to the onset of AD symptoms will slow or prevent the decline of cognitive and functional abilities. The five-year study is in collaboration with the Banner Institute and is funded by the National Institute on Aging.
“We are extremely disappointed about the outcome of the Phase III CREAD 1 interim analysis and we also would like to thank patients and caregivers for their participation. We continue to be optimistic about the potential future of crenezumab as we await the outcome of the Colombian API study to prevent AD symptoms in patients with familial AD to see if the antibody treatment may provide disease-modifying effects in patients with early-onset disease. We remain committed to our ongoing pre-clinical and clinical candidates targeting Tau and neuro-inflammation to treat Alzheimer's disease, neuro-orphan diseases and Parkinson’s disease,” added Prof. Andrea Pfeifer, CEO of AC Immune.