The Dominantly Inherited Alzheimer’s Network announced on Oct. 10 three experimental medications that will be used in a forthcoming primary prevention study in asymptomatic patients who carry an autosomal dominant mutation. The announcement represents a landmark event in which experimental therapeutics have been redirected from treating patients with established symptoms and disease to those at the highest risk who are currently asymptomatic.
This follows closely on the heels of the recently announced Alzheimer’s Prevention Initiative (API), led by Dr. Eric Reiman and Dr. Pierre Tariot of the Banner Alzheimer’s Institute in Phoenix, Ariz. In May of this year, the API was described by the National Institute on Aging as the "cornerstone" of the government’s efforts to prevent Alzheimer’s disease. Both research programs have focused efforts on treating amyloid, a strategy that makes perfect sense in these individuals given the known pathogenic mutation they carry that specifically causes Alzheimer’s disease by massively increasing cerebral amyloid levels.
Dr. Richard J. Caselli
The Dominantly Inherited Alzheimer’s Network (DIAN) Therapeutic Trials Unit, led by Dr. Randall Bateman of Washington University, St. Louis, will test monoclonal antibodies from Roche (gantenerumab) and Eli Lilly (solanezumab) as well as a beta-secretase inhibitor, also developed by Eli Lilly. Given the recent discovery of a disease-preventative mutation affecting beta-secretase activity, this adds even further to the field’s excitement and anticipation.
Solanezumab failed to achieve its primary end points in a recently reported trial, but did achieve a preplanned secondary end point suggesting it may possibly slow disease progression by about 34%. As exciting as this, or any actual progress against what has been an immovable enemy may be, some practical perspective is needed. Slowing disease progression to a modest degree is still a far cry from a cure. Other immunomodulatory agents, including monoclonal antibodies and intravenous immunoglobulin, are massively expensive. Rituximab, for example, costs roughly $60,000 for a treatment cycle for one patient. If every one of the 5.4 million Alzheimer’s patients alive in the United States today received one cycle, the cost would be $324 billion, far more than the current annual total cost of care. If this were to eliminate the disease, one might even consider it a bargain, but it will not. Just as existing symptomatic therapies provide marginal symptomatic benefit, the degree of benefit that drugs like solanezumab appear to provide would be barely perceptible by real patients and their families. We desperately need a cure, a real cure, and the promise of early intervention is that it will stop the disease before it gains a foothold. We all watch in rapt anticipation as these efforts launch.
Dr. Caselli is professor of neurology at the Mayo Clinic, Scottsdale, Ariz., and is the clinical core director of the Arizona Alzheimer’s Disease Center. He has no relevant disclosures.