AC Immune SA announced results from the Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) Colombia Trial. The study evaluated the potential of crenezumab, an investigational medicine, to slow or prevent Alzheimer's disease in cognitively unimpaired people who carry a specific genetic mutation which causes early-onset Alzheimer's disease. Numerical differences favouring crenezumab over placebo were observed across the co-primary, multiple secondary and exploratory endpoints, though none were statistically significant.

The co-primary endpoints assessed the rate of change in cognitive abilities or episodic memory function, measured by the API ADAD composite cognitive total score and the Free and Cued Selective Reminding Test (FCSRT) Cueing Index, respectively. Crenezumab was generally well tolerated during the study and no new safety issues were identified. Further analyses of data are ongoing.

Initial data will be presented at the Alzheimer's Association International Conference (AAIC) on August 2, 2022. The trial enrolled 252 people who are members of the world's largest extended family with ADAD in Colombia. Two-thirds of participants carried the Presenilin 1 E280A mutation which typically causes cognitive impairment due to Alzheimer's disease around age 44.

Participants were randomised to receive crenezumab or placebo over five to eight years. During the trial, the dose of crenezumab was increased as knowledge about potential treatment approaches for Alzheimer's disease evolved. The study, which was supported by National Institute on Aging, generous philanthropic contributions to Banner Alzheimer's Foundation, and Roche, has generated a wealth of data that will advance the early detection, tracking and study of Alzheimer's disease and inform the design of future Alzheimer's prevention trials.

Crenezumab is an investigational treatment discovered by AC Immune SA and designed to neutralise a pathological species of the beta-amyloid protein called oligomers. It is developed by Genentech, a member of the Roche Group, under a license and collaboration agreement established in 2006. The Alzheimer's Prevention Initiative (API) is an international collaborative formed in 2009 to launch a new era of Alzheimer's prevention research.

Led by the Banner Alzheimer's Institute, the API conducts prevention trials in cognitively healthy people at increased risk for Alzheimer's disease. API continues to establish brain imaging, fluid biomarker and cognitive endpoints needed to rapidly test promising prevention therapies. It also leads participant recruitment registries to accelerate enrollment into Alzheimer's-focused studies.

API is intended to provide the scientific means, accelerated approval pathway and enrollment resources needed to evaluate the range of promising Alzheimer's prevention therapies and find ones that work without losing another generation. First proposed by investigators from BAI, the API ADAD trial (NCT01998841) was a prospective, randomised, double-blind, placebo-controlled, parallel-group label enabling Phase II study of the efficacy of crenezumab versus placebo in cognitively unimpaired individuals who have no clinical symptoms of Alzheimer's disease and carry the PSEN1 E280A autosomal dominant mutation. Participants who are mutation carriers were randomised in a 1:1 ratio to receive either crenezumab or placebo for at least 260 weeks.

Crenezumab was initially administered subcutaneously 300 mg every two weeks. Dosing was amended in 2015 to 720 mg subcutaneously every two weeks and in 2019 the option to increase the dose to 60 mg/kg, delivered intravenously every four weeks, was offered to participants. A cohort of participants (non-mutation carriers) were also enrolled and dosed solely on placebo.

The trial, which was supported by National Institute on Aging's (NIA) generous philanthropic contributions to Banner Alzheimer's Foundation and Roche, was the first NIH-supported prevention trial of an experimental prevention therapy in cognitively unimpaired persons at known risk for the disease.