This is the first time investigators will test an amyloid-clearing drug in older individuals thought to be in the pre-symptomatic stage of Alzheimer’s disease. The trial will enroll older individuals with evidence of amyloid in their brains – a hallmark of Alzheimer’s disease – but who do not show clinical symptoms of the disease. The trial is funded by the National Institutes of Health (NIH), part of the US Department of Health and Human Services, and by private sector contributions.
“We carefully considered a number of promising anti-amyloid treatments for the A4 trial over the past six months.” said Reisa Sperling, MD, principal investigator for the A4 trial, and the director of CART at BWH. “Our committee ultimately reached the decision that solanezumab was the best choice for this first trial in asymptomatic people at high risk for cognitive decline.”
Earlier this week the National Institutes on Aging, the lead NIH institute on Alzheimer’s research, announced funding for the three-year A4 trial, which will enroll 1,000 patients, ages 70-85, who have evidence of the abnormal amyloid protein building up in the brain detected on PET scans. The A4 trial will be facilitated by the Alzheimer’s Disease Cooperative Study (ADCS), a consortium of academic Alzheimer’s disease clinical trial centers, led by Paul Aisen, MD at University of California, San Diego. The ADCS was established by the NIH in 1991 to advance research on the treatment of Alzheimer’s disease.
“Solanezumab has a good safety profile, and we were encouraged by the evidence of a modest clinical benefit in the mild Alzheimer’s disease dementia patients in the Phase 3 trials.
Our confidence level in solanezumab grew after the results were confirmed through an independent, academic analysis by the ADCS released in early October,” said Sperling, who is also a professor of Neurology at Harvard Medical School and the director of the Harvard Aging Brain Study at the Massachusetts General Hospital and BWH. “We hope that starting treatment much earlier in the disease, before symptoms are present, as well as treating for a longer period of time, will slow cognitive decline and ultimately prevent Alzheimer’s disease dementia.”
The A4 researchers also announced that they will use florbetapir as the PET amyloid tracer to select participants for the trial. Florbetapir is an FDA approved PET imaging agent for detecting the presence of absence of amyloid in the brains of patients with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline. It is also being used in several other large academic studies. Keith Johnson, MD from Massachusetts General Hospital will lead the PET amyloid imaging aspects of the A4 trial. Drs. Sperling and Johnson made the announcement about the selection of solanezumab and florbetapir at the 7th Annual Human Amyloid Imaging meeting on January 18 in Miami.
“This large scale study would not be possible without public-private partnerships,” Sperling said, “Alzheimer’s disease is a looming public health crisis, and this is a great example of how academia, government and industry can work together towards finding a successful treatment.”
Solanezumab is a monoclonal antibody in Phase III clinical trials. Discovered and developed by Eli Lilly and Company, it binds to soluble monomeric forms of amyloid beta after it is produced, allowing it to be cleared before it clumps together to form plaques. AmyvidTM (florbetapir F 18 injection) is developed and manufactured by Avid Radiopharmaceuticals, Inc., which was acquired as a wholly owned subsidiary of Lilly in 2010.
Brigham and Women’s Hospital