Data from six additional months of treatment with an experimental drug for Alzheimer’s disease were enough to turn a failed mid-stage clinical trial into a possible success. On Wednesday, the Japanese pharmaceutical company Eisai and its U.S.-based partner, Biogen, explained how, providing details that point to ways that their drug, unlike many before it, might succeed in a larger test.
In a Phase 2 study, the Alzheimer’s drug BAN2401 reduced measures of amyloid protein buildup in the brain—this buildup is associated with the progression of the disease. The companies said that those results—across all doses of the drug—were statistically significant. Furthermore, the drug slowed cognitive decline by 30 percent in patients treated with the highest dose. These, however, were only secondary goals of the study (more about the caveats below).
Pierre Tariot, director of the Banner Alzheimer’s Institute, called the results “heartening,” but he cautioned that questions remain and more analysis is needed. Nonetheless, he said the data so far are encouraging for BAN2401, and for other antibody drugs in clinical testing for Alzheimer’s.
“This is a finding that is going to stimulate further investment about what anti-amyloid therapies will have what effects,” Tariot said. “I think it will stimulate more investment and more focused investigation.”
The results from the BAN2401 study, presented during the Alzheimer’s Association International Conference (AAIC) in Chicago this week, are being closely watched by investors, Alzheimer’s researchers, and patients alike. They represent one of the few times in clinical testing that an Alzheimer’s drug has shown that it might improve patients’ ability to function, not just clear up the clumps of proteins that are the hallmarks of the memory-robbing disease. Shares of Cambridge, MA-based Biogen (NASDAQ: [[ticker:BIIB]]) closed 2.95 percent higher than Tuesday’s closing price, then fell more than 11 percent in after-hours trading as the investment community processed the data.
The results come with important caveats. They are from a Phase 2 test that failed its main goal of improving patients’ cognition after 12 months. Eisai and Biogen continued the trial and found that the patients given the highest dose of BAN2401 saw their cognition—and other measures of their mental faculties—improve after 18 months of treatment, compared to placebo patients. However, Eisai and Biogen used two different methodologies to measure cognition in its study, which makes it more difficult to draw definitive conclusions about the drug.
The cognitive decline seen at the highest dose of BAN2401 exceeded investors’ expectations, wrote Leerink analyst Geoffrey Porges. But other details have caused confusion. The drug didn’t show a “dose response,” for example, meaning getting incrementally higher doses didn’t necessarily mean better results. The data “once again call the reliability of this result and any associated inferences into question,” Porges wrote.
BAN2401 is an antibody drug meant to break up the clumps, also called plaques, of amyloid protein that build up in the brains of Alzheimer’s patients. The popular “amyloid hypothesis” often used to explain the underlying cause of Alzheimer’s holds that breaking up these plaques and clearing them from the brain might slow, or even stop, the disease’s progression. BAN2401 is meant to bind to the clusters of proteins that go on to form amyloid plaques.
Yet every single drug meant to bust up amyloid plaques has failed in clinical testing, often after promising signals in early studies couldn’t be replicated in a final Phase 3 test. In the past two years alone, solanezumab from Eli Lilly (NYSE: [[ticker:LLY]]); verubecestat from Merck (NYSE: [[ticker:MRK]]); intepirdine from Axovant Sciences (NASDAQ: [[ticker:AXON]]); and Lundbeck’s idalopirdine have all failed late-stage studies. Those failures have challenged the amyloid hypothesis and prompted researchers to rethink whether targeting amyloid plaques is the right way to treat Alzheimer’s. But Eisai and Biogen’s report of success with BAN2401—and Biogen’s encouraging early results with another experimental drug, aducanumab— have, for now, kept hopes alive that an amyloid approach could work.
The Phase 2 study of BAN2401 split 856 patients—who had early Alzheimer’s and signs of amyloid—into six different groups. Five of those groups got different doses of the drug via a 60-minute infusion, and the sixth group got a placebo. The main goal of the study was to show a positive change, compared to placebo, in a score measuring their cognitive function. By that measure, the drug failed the study at the 12-month mark. But when Biogen and Eisai announced those results last December, the companies also said none of the conditions for stopping the study were met, so they decided to keep going to see if they could learn more.
Showing a meaningful benefit on cognitive function after 18 months of treatment was
