FDA approves Biogen’s Alzheimer’s drug aducanumab

In a controversial and historic decision, the US Food and Drug Administration has approved Biogen’s Alzheimer’s drug aducanumab, which will be sold under the trade name Aduhelm. It is the first new therapy for Alzheimer’s disease in nearly two decades, and the first approved drug that reduces amyloid-β plaques in the brain, which some scientists believe are the underlying cause of the disease.

Aducanumab is not a cure. It won’t reverse memory loss in people who already have Alzheimer’s, and it’s debatable whether the drug is even effective at slowing cognitive decline. But the FDA chose to let the antibody onto the market based on its ability to clear amyloid plaques—the hallmark buildup of proteins in the brains of people with the disease. Aducanumab reduced the plaques by 59% in one study, and by 71% in another study.

The FDA’s decision defies the recommendation of its expert panel, which convened in November 2020 to discuss Biogen’s Phase 3 clinical trial data for aducanumab. That committee voted against approving the drug, and three members reiterated the case in an editorial that ran in late March in the Journal of the American Medical Association. The panel argued that data from the two studies failed to show the drug could improve cognition in people with Alzheimer’s.

Excitement around aducanumab began in 2015 when Biogen announced evidence of the drug’s ability to reduce amyloid-β in the brains of people with mild Alzheimer’s disease. Biogen then launched two Phase 3 clinical trials to see if the drug could slow cognitive decline. The firm pulled the plug on the trials in March 2019 after determining that the drug wasn’t working.

But in October Biogen reversed course and said that it was initially wrong. Upon closer examination of the clinical data, Biogen determined that a high dose of aducanumab in one of the two trials slowed, but didn’t stop, cognitive decline. The drug still didn’t show benefit in the other trial.

Since that announcement, neuroscientists and statisticians have debated Biogen’s conclusions. Some argue aducanumab offers no real benefit, while others say the drug holds promise, but that Biogen needs more data to prove its worth. Advocacy groups say aducanumab’s benefit is real and that the drug will help give individuals with Alzheimer’s and their families more time together. Health economists have voiced concerns that a minimally effective drug would place massive financial strain on the healthcare system.

Although the approval was based on studies in people with mild Alzheimer’s, the FDA gave Aduhelm a broad label, meaning it can be used by people with any stage of disease—including those whose disease is so advanced that they are unlikely to see any benefit. People are required to have their disease confirmed by an MRI scan before the first, monthly infusion, and are expected to get follow-up scans after around 6 months and a year of treatment.

In a press conference, Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research (CDER), said aducanumab “consistently and convincingly” reduced amyloid plaques in a dose- and time-dependent fashion in people with Alzheimer’s. At the same time, she emphasized that the approval comes with an asterisk: Biogen must conduct another clinical study to prove to the agency that reducing amyloid plaques actually helps people with Alzheimer’s.

Peter Stein, director of CDER’s Office of New Drugs, said the reduction of amyloid plaque was likely tied to clinical benefit—meaning that the disease was progressing more slowly. He also said the FDA expects that Biogen’s follow-up trial will confirm that benefit.

Addressing the controversial nature of the approval head on, Cavazzoni said the FDA is aware of “the extraordinary level of interest and steady volume of commentaries” on the agency’s review of aducanumab.

“The data was very complex, and our review has been thorough,” she said, while emphasizing the agency’s commitment to hearing different opinions on the data during the review. The FDA was ultimately convinced that there was enough evidence to grant the drug an accelerated approval and let people with Alzheimer’s and their families decide whether the therapy is right for them, she said.

For many experts, the approval is confounding. “Not only does it not work, but it looks to be unsafe,” says Joseph Ross, a member of the Center for Outcomes Research and Evaluation at the Yale-New Haven Hospital, and co-director of the National Clinician Scholars program at Yale University. Some people in Biogen’s trials experienced brain swelling, a serious side effect that Ross says will be harder to detect in the real world. “There’s a real risk of patient harm.”

Howard Fillit, founding executive director and chief science officer at the Alzheimer’s Drug Discovery Foundation, is circumspect about the data supporting aducanumab and said people with Alzheimer’s and their families “should know that the incremental benefit that aducanumab provides is going to be followed in the coming years by other drugs that will build on its impact.

“We’re at an amazing time in the history of drug development for Alzheimer’s disease,” Fillit says. More than half of the roughly 120 drugs in clinical trials work by a mechanism distinct from targeting amyloid plaques or tau—a protein that forms tangles in the brains of people with Alzheimer’s. Many experimental drugs target neuroinflammation or protein misfolding, while others aim to protect brain cells that are still working well. He says patients will truly benefit when they can take multiple medications that address the various ways the brain can break down.

The benefits of aducanumab for people with Alzheimer’s might be murky, but one clear winner is Biogen, which made a huge bet that the antibody would reach the market. In 2015, with only early-stage data in hand, Biogen’s then CEO George Scangos said the firm likely would invest some $2.5 billion in manufacturing capacity and clinical trials to get the drug to market.

The company says Aduhelm, which stock analysts believe could bring in over $8 billion annually by 2025, will cost roughly $56,000 per year. Biogen’s stock was up over 57% following the FDA’s news.