Alzheimer’s drug resurrected, as company claims clinical benefits

Biogen stunned investors and scientists alike today, announcing it will resurrect an Alzheimer’s drug it had declared a failure in March; the company plans in early 2020 to ask the U.S. Food and Drug Administration for marketing approval of aducanumab, an antibody designed to bind and eliminate the protein beta-amyloid in the brain.

As STAT reports, Biogen says the about-face came after it assessed clinical trial data from a larger number of patients than it first analyzed. Whereas an initial “futility” analysis of data from two late-stage clinical trials found that the drug failed to meaningfully slow progression of early Alzheimer’s disease, the company now concludes that, due primarily to the responses of people on the higher of two doses of the antibody, the drug did significantly slow people’s cognitive decline and their functional decline, meaning their ability to cope with activities of daily living.

Biogen’s first analysis used data from 1748 patients who had completed 18 months on a low dose or a high dose of the drug; the new analysis, whose underlying data are not yet publicly available nor described in a journal article, included 2066 such patients.

The Alzheimer’s Association in Chicago, Illinois, declared itself “encouraged” by the announcement. “We eagerly anticipate reviewing a full report of the findings” it said in a press release.

Bart De Strooper, who directs the UK Dementia Research Institute at University College London, called the news “fantastic. … We currently have no effective treatments to slow or halt the progression of Alzheimer’s disease and I hope this signifies a turning point.” He also suggested the result could revive the once-dominant theory that the neurodegenerative condition is largely due to the brain’s accumulation of toxic amyloid. “We should now redouble our efforts to tackle this central problem in Alzheimer’s disease.”

Biogen’s announcement comes as researchers discuss therapeutic prospects for Alzheimer’s at the annual meeting of the Society for Neuroscience in Chicago. “It’s very exciting,” says neuroscientist Weiming Xia of Boston University School of Medicine. Should aducanumab win approval, researchers will be able to evaluate the antiamyloid strategy in a much broader group of patients—and identify subpopulations that are most likely to benefit, Xia says. “If you use one antibody for all Alzheimer’s patients, it will not work.”

Others at the meeting remain skeptical that the drug—and the underlying amyloid hypothesis—will pan out. “Why [Biogen] came back now and said they would pursue what before they themselves they tried to discard—it seems, to me, strange,” says Nikolaos Robakis, a neuroscientist at the Icahn School of Medicine at Mount Sinai in New York City. "But if the data supports the claim, it will be a positive development to our search for therapeutics," he adds. In a presentation today, Robakis proposed that beta-amyloid plaques—and another Alzheimer’s hallmark, the buildup of protein tau inside neurons—are not causes of neurodegeneration but consequences of an underlying vulnerability to stress in the brain. Already, he says, the failures of other trials that took the antiamyloid strategy suggest “the evidence is stacked against it.”

Biogen says it plans to reveal more details of its latest analysis at an upcoming scientific conference.