How CAD106 works
CAD106 is designed to stimulate the production of antibodies against beta-amyloid, while avoiding an immune response against the recipient’s cells and tissues (called an autoimmune response). Beta-amyloids are protein pieces that clump together, forming plaques that are thought to be harmful to nerve cells.
CAD106 is composed of a short fragment of beta-amyloid, that includes only the amino acids 1 to 6 (amino acids are the building blocks of proteins). It is hoped that the antibody response triggered by the vaccine will break down beta-amyloid plaques in a patient’s brain and prevent new plaques from forming.
Preclinical evidence gathered in animal studies suggests that CAD106 can reduce beta-amyloid accumulation in the brain by inducing antibodies that interfere with beta-amyloid deposits and by binding to beta-amyloid aggregates.
CAD106 in clinical trials
Two Phase 2 randomized and placebo-controlled clinical trials of CAD106 (NCT00733863 in Europe, and NCT00795418 in the U.S, both sponsored by Novartis) were initiated in 2008, and their open-label extension studies (NCT00956410 and NCT01023685) lasted through to 2011 and 2012, respectively.
The main purpose of these trials was to the assess the safety and tolerability of multiple doses of CAD106, and to measure the degree of the antibody response it generated against beta-amyloid. Results showed that the vaccine was generally safe, well-tolerated, and triggered antibody responses to beta-amyloid in 63.8 percent of those treated with no evidence of autoimmune reactions. However, no differences were seen between the treatment and placebo groups on cognitive decline and brain volume.
A Phase 2/3 clinical trial (NCT02565511), called the Generation Study, is currently recruiting people at risk of Alzheimer’s at sites across the U.S., Canada, and Europe. It will separately test if CAD106 and another investigative medication, CNP520 from Amgen, can prevent Alzheimer’s in people, ages 60 to 75, who are cognitively healthy but have two APOE4 genes. APOE4 is a variant of the APOE gene found in a number of Alzheimer’s patients. People with two copies of the APOE4 gene variant are considered to be at high risk of developing mild cognitive impairment (MCI) and/or dementia due to Alzheimer’s disease. MCI is a slight decline in cognitive ability, including thinking and memory skills.
One part of the study will compare 430 given CAD106 as an injection to 260 individuals who will receive a placebo; another will compare against placebo 390 people treated with oral CNP520. The study will follow participants for at least 60 months (5 years) and up to 96 months (8 years). Generation Study is expected to conclude in May 2024.
Effects of the therapy on cognition, global clinical status, and underlying pathology will also be assessed. Primary endpoints are time to diagnosis of MCI or dementia due to Alzheimer’s, and changes in the Alzheimer’s prevention initiative composite cognitive (APCC) test scores at 60 months after treatment start. The APCC test is considered a sensitive tool to detect and track cognitive decline in individuals at risk for progression to stages of Alzheimer’s.
Secondary outcome measures will assess cognition, biomarkers of disease progression, and antibody response to beta-amyloid.
The study is supported by Novartis, Banner Alzheimer’s Institute, National Institute on Aging (NIA), Alzheimer’s Association, and Amgen. Enrollment information is available by clicking here, or on the trial’s identification number.
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