Biogen announced today that it had submitted a biologics license application to the U.S. Food and Drug Administration for aducanumab, a therapeutic antibody developed to clear amyloid plaques from the brain. The Cambridge, Massachusetts, biotech company, in partnership with Eisai Co. Ltd., Tokyo, has requested a priority review, which could mean an FDA decision within six months. If approved, this would be the first biologic, first anti-amyloid treatment—and the first new drug for Alzheimer’s disease in more than 16 years in the U.S., since Namenda was approved in 2003. A seaweed extract was recently approved to treat AD in China (Nov 2019 news).
Getting here has not been smooth sailing for Biogen, and the filing has proven controversial (Dec 2019 news and comments). In March 2019, Biogen stopped development of aducanumab after a futility analysis predicted that its two Phase 3 Trials, EMERGE and ENGAGE, would miss their primary endpoints of slowing dementia as judged by the CDR sum of boxes (March 2019 news). In October that year, the company took a U-turn, reporting that the highest dose, when given for the whole treatment period, or 14 times, had indeed slowed cognitive decline a bit in EMERGE. Patients on the highest dose of aducanumab in the smaller ENGAGE trial continued to decline as fast as those on placebo (Oct 2019 news). Biogen argued that the participants in ENGAGE had not been on the highest dose of the drug for long enough to experience a benefit (Dec 2019 news).
Expert commentators have cautioned that interpretation of the data is tricky because the Phase 3 studies increased doses midway through, stopped early, and lacked power in post hoc analysis of subgroups. The unusual aspects of this dataset, coupled with the relatively small cognitive/clinical effect size and the possibility that some patients might have become unblinded to treatment because they developed mild inflammation of the brain, will make it difficult to draw conclusions. But aducanumab’s ability to remove brain amyloid is beyond question, the medical need is enormous, and a great sense of expectation has built up in recent years. The task of navigating the data amid the competing pressures is now in the hands of the FDA. The agency will likely convene an expert panel to review the application.—Tom Fagan
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