Crenezumab Did Not Slow or Prevent of Cognitive Decline in People with Autosomal Dominant Alzheimer Disease

In the Alzheimer Prevention Initiative (API) Autosomal Dominant Alzheimer Disease (ADAD) Colombia trial (NCT01998841), crenezumab (Genentech, South San Francisco, CA) did not affect cognitive decline in people with a specific genetic mutation that causes early-onset Alzheimer disease (AD). The API ADAD trial was a phase 2 study of the efficacy of crenezumab vs placebo in individuals without cognitive impairment who carry the presenilin 1 (PSEN1) E280A autosomal dominant mutation. 

“We’re disappointed that the treatment did not demonstrate a statistically significant clinical benefit,” said Eric M. Reiman, MD, Banner Alzheimer Institute executive director and one of the study leaders. “At the same time, we’re proud of the impact that this precedent-setting trial has had in shaping a new era in AD prevention research and we’re extremely grateful to our research participants and their families. 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.”  

Participants were randomly assigned to receive crenezumab or placebo and treated for 5 to 8 years. Crenezumab was initially administered subcutaneously 300 mg every 2 weeks initially and then amended to 720 mg subcutaneously in 2015. In 2019, the option to have 60 mg/kg intravenously every 4 weeks was offered to participants. 

The rate of change in cognitive abilities or episodic memory function was measured by the API ADAD composite cognitive total score and the Free and Cued Selective Reminding Test (FCSRT) cueing index.

Crenezumab is a monoclonal antibody to beta amyloid oligomers and was generally well tolerated with no identifiable new safety issues. Initial data will be presented at the Alzheimer Association International Conference (AAIC) on August 2, 2022.