Dr. Michael Fulks, Consulting Medical Director, discusses the latest results for the use of lecanemab in early Alzheimer’s disease.
Beta amyloid accumulates into plaques in the brain leading to tau tangles resulting in Alzheimer’s dementia or so the current most popular (but still very much unproven) theory goes. Various monoclonal antibodies designed to remove beta-amyloid plaques have been or are in trials trying to improve cognition in Alzheimer’s disease or prevent its development. The latest results for lecanemab have recently been reported in the NEJM and popular media.
Unlike results for prior antibody trials, lecanemab showed positive results in a cohort with early Alzheimer’s disease manifesting as mild cognitive impairment or mild dementia. This is thought to be the best target population. There was a 50% reduction in brain amyloid seen on PET scan. Of more relevance, there was also a 27% reduction in cognitive worsening over 18 months. This is not an improvement in cognition or even stability despite the substantial reduction in amyloid but only a small reduction in the still relentless pace of the disease. The downsides of lecanemab include temporary brain swelling and brain microhemorrhage occurring in 17% of participants which, while concerning, seems to resolve as well as the need for continuing IV infusions of lecanemab every 2 weeks.
Based on preliminary communications from the manufacturer, the annual drug cost would be $26,500 plus the cost of infusions every two weeks and safety monitoring which will add many thousands of dollars to the drug cost and use up substantial medical and patient support resources. There will also be no way to monitor efficacy for a single patient or to decide on a stopping point as improvement or stability is not expected. The hoped-for small gradual reduction in cognitive worsening cannot be differentiated from no impact or even an adverse impact.
So, we are left still not being sure attacking amyloid is the answer. We also have a drug that will have very high ongoing cost, concerning side effects and heavy use of resources with, at best, a small and unmeasurable benefit for any single patient. As of July 6, 2023, lecanemab has received traditional approval from the FDA.
About the Author
Michael Fulks, MD, Consulting Medical Director, is board-certified in internal and insurance medicine. After leaving practice, he served as a medical director, creating or editing several underwriting manuals and preferred programs. More recently, Mike has consulted for CRL participating in its mortality research on laboratory test results, BP and build, and in the development of risk-scoring tools for laboratory and non-laboratory data.