A University and government-led consortium announced the start of two new clinical trials testing an Eisai and Biogen Alzheimer’s disease drug in people who have shown no signs of the neurodegenerative disorder. The Phase 3 studies will take more than four years to yield data.The two trials will test the therapy, called BAN2401, in people with signs of brain accumulation of a protein called amyloid beta, which some experts believe is the cause of cognitive decline in Alzheimer’s. This hypothesis is intensely debated because so many experimental drugs that block amyloid accumulation haven’t worked, although Biogen and Eisai are making the case to regulators that one, called aducanumab, has. Trials of amyloid-blocking drugs in pre-symptomatic patients have been no more promising than those in patients with signs of disease. Most recently, Eli Lilly’s drug solanezumab failed in the preventive DIAN-TU trial, which took eight years to yield results.
The new clinical program is called AHEAD 3-45, and consists of two separate trials of patients with signs of amyloid accumulation. The first, dubbed A3, will test BAN2401 in people with undetectable levels of amyloid in the brain but who are at risk of accumulation. The other, called A45, will enroll individuals with elevated amyloid and at risk of disease progression.
The trials, which will enroll 1,400 patients in total, will compare BAN2401 to placebo. In A3, the goal will be to detect a difference in amyloid levels, while A45 will use a clinical test to measure cognitive decline in participants who have no signs of disease at baseline.
BAN2401 is a synthetic antibody that binds with amyloid beta “protofibrils,” a form of the protein that is thought to be especially toxic to nerve cells. The drug is designed to prevent the accumulation of amyloid brain plaques that are considered to be characteristic of Alzheimer’s disease.
The Alzheimer’s Clinical Trial Consortium, funded by the National Institute on Aging, will run the trial along with Japanese drugmaker Eisai. The University of Southern California and Brigham and Women’s Hospital in Boston will coordinate study of the drug.
USC’s Alzheimer’s Therapeutic Research Institute already has a prevention trial underway called A4, testing Eli Lilly’s solanezumab in patients with elevated amyloid levels. Unlike many earlier prevention trials, USC’s work does not focus on patients with uncommon mutations that can lead to early or more severe disease.
Because Alzheimer’s disease typically results in slow cognitive decline, studies can take years to yield results even in symptomatic patients. In pre-symptomatic patients testing can take even longer: A4 began enrolling patients in 2014 and expects to have data in 2022.
In the case of the two new trials, the data are expected to be based on testing taken 216 weeks after a baseline evaluation.
Meanwhile, Eisai and Biogen last year initiated the first Phase 3 trial of BAN2401 in patients with early Alzheimer’s disease, despite mixed data that emerged from mid-stage trials.
Since then, BAN2401 has been largely eclipsed by the story around aducanumab, which was dramatically revived by the companies after an initial look at the drug’s studies had led to their early halt. Biogen recently completed its submission of the drug to the Food and Drug Administration, which now has two months to decide whether it will conduct an approval review.