Crenezumab Fails to Show Benefit for Alzheimer’s Disease

Genentech’s anti-amyloid crenezumab did not slow or prevent cognitive decline in people with early-onset Alzheimer’s disease.

Crenezumab did not demonstrate a statistically significant clinical benefit in either of its co-primary endpoints assessing the rate of change in cognitive abilities or memory function, according to the results of a new clinical trial.

The trial, conduct by Genentech and Banner Alzheimer’s Institute, evaluated the potential of crenezumab to slow or prevent Alzheimer’s disease in people who carry a specific genetic mutation, which causes early-onset Alzheimer’s disease.

Small numerical differences favoring crenezumab were observed across the co-primary and multiple secondary and exploratory endpoints, but these were not statistically significant. No new safety issues were identified with crenezumab during the study.

Crenezumab is an investigational, monoclonal antibody designed to neutralize neurotoxic oligomers, a form of beta-amyloid. Crenezumab has an antibody backbone (IgG4) designed to minimize the inflammatory response in the brain.

Data will be presented at the Alzheimer's Association International Conference on Aug. 2, 2022.

“We’re disappointed that the treatment did not demonstrate a statistically significant clinical benefit,” Eric M. Reiman, M.D., Banner Alzheimer’s Institute executive director and one of the study leaders, said in a press release. “This trial, the data, samples and findings that we’ll share with the research community, and the related work that we and others are doing promise to further accelerate the evaluation and approval of future prevention therapies.”

This follows ongoing controversy over Biogen’s anti-amyloid Aduhelm (aducanumab-avwa), which was approved by the FDA in June 2021 although an advisory committee voted against approval. The trials showed the therapy reduced amyloid plague in the brain, but the trials were inconclusive about the impact of this on cognitive decline. One study met the primary endpoint, showing reduction in clinical decline, while the second trial did not meet the primary endpoint.

Genentech’s study, the Alzheimer’s Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) Colombia Trial, enrolled 252 people who are members of the world’s largest extended family with ADAD in Colombia. Two-thirds of patients carried the Presenilin 1 E280A mutation, which typically causes cognitive impairment due to Alzheimer’s disease around age 44.

Genentech is also evaluating the potential of gantenerumab in autosomal dominant Alzheimer’s disease, as well as for the prevention of sporadic Alzheimer’s and treatment of early Alzheimer’s disease. Gantenerumab is an investigational IgG1 antibody designed to bind to aggregated forms of amyloid beta and remove brain amyloid plaque. Results from the phase 3 GRADUATE studies of gantenerumab in early Alzheimer’s disease are expected in the fourth quarter of 2022.