Update (June 14): Three members of the US Food and Drug Administration advisory committee that recommended against the approval of aducanumab have resigned in protest, according to The New York Times: Joel Perlmutter of Washington University School of Medicine, David Knopman of the Mayo Clinic, and Aaron Kesselheim of Harvard Medical School and Brigham and Women’s Hospital.
The US Food and Drug Administration has approved aducanumab, a monoclonal antibody going by the brand name Aduhelm, to treat Alzheimer’s disease in early-stage patients. The announcement today (June 7) marks the first time in 17 years that the FDA has approved a drug to treat the neurodegenerative disease.
“After so many disappointments in potential treatments, the Alzheimer’s community now knows this deadly enemy has finally been engaged. At long last, science and time are on our side,” UsAgainstAlzheimer’s, an advocacy organization, says in a statement.
That enthusiasm is tempered by a number of experts who say the drug has not been shown to make a meaningful difference to patients. Caleb Alexander, an FDA adviser and researcher at Johns Hopkins University, recommended against the drug’s approval. “The FDA gets the respect that it does because it has regulatory standards that are based on firm evidence. In this case, I think they gave the product a pass,” he tells the Associated Press.
Aducanumab clears amyloid plaques in the brain, and data from an early clinical trial showed that it’s strikingly effective at doing so. “Overall, this is the best news that we’ve had in my 25 years of doing clinical research,” Stephen Salloway, a physician at Butler Hospital in Providence, Rhode Island, who led the study, said in 2016 when those results were published.
But later results from two Phase 3 studies indicated that aducanumab wasn’t making enough of a difference to recipients’ mental abilities, and in 2019 Biogen and Eisai, the drug’s developers, stopped the trials. Half a year later, and after a new look at the data, the companies determined that participants who’d received the highest dose of the drug experienced less cognitive decline, along with less amyloid and tau proteins in their brains, compared to participants who received a placebo.
The companies decided to pursue regulatory approval, but in November 2020, the FDA panel that Alexander sits on recommended against it, noting that only one of the two clinical trials showed any benefit.
The agency nevertheless went ahead with approval, but with strings attached. As STAT notes, the approval is based on aducanumab’s ability to clear amyloid plagues, and the companies will need to continue testing and demonstrate clinical benefit to keep the drug on the market. “In approving the drug on a conditional basis, the agency departed from decades of regulatory precedent,” STAT reports, “setting a new bar for treatments with considerable potential but unproven benefits—a standard that could also be applied to other devastating diseases.”