What to know about the fallout from the FDA decision to approve Biogen’s Alzheimer’s drug

The Biogen headquarters in Cambridge.CODY O'LOUGHLIN/NYT

Three members of a US Food and Drug Administration advisory panel, including a Harvard Medical School professor, resigned this week over the agency’s decision on Monday to approve Cambridge-based Biogen’s controversial Alzheimer’s disease drug.

Here’s what you need to know about the fallout from the decision.

Who has resigned from the advisory panel?

Aaron Kesselheim, a Harvard Medical School professor, resigned from his role on an FDA advisory committee in a letter to Janet Woodcock, the agency’s acting commissioner, on Thursday. In the letter, he said the FDA’s Biogen decision “was probably the worst drug approval decision in recent U.S. history.”

Kesselheim was the third member to resign this week. Business Insider reported on Wednesday that David Knopman, a neurologist at the Mayo Clinic, was resigning from his advisory role over the decision. And STAT News reported that committee member Joel Perlmutter, a neurologist at Washington University in St. Louis, quit on Monday, the same day of the FDA ruling.

What does this advisory panel do?

The resignations stemming from the Biogen drug approval are coming from the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee. This committee reviews data about the safety and efficacy of drugs that aim to treat neurological diseases, such as Alzheimer’s. The FDA has a total of 47 advisory committees, which provide independent advice and recommendations to the federal agency.

Members of these committees are appointed for one-to-four-year terms. Kesselheim’s term was set to expire in January 2023, and Knopman and Perlmutter’s terms would have expired in January 2022.

What was the panel’s position on the Biogen drug?

The 11-member panel met in November and, in a series of votes, concluded that Biogen failed to prove its experimental drug for Alzheimer’s disease was effective. Notably, the committee voted 10-0, with one member voting “uncertain,” that the results from the company’s late-stage clinical trial should not be relied on as “primary evidence of effectiveness” for the medicine.

At the time, Dr. Scott Emerson, a professor emeritus of biostatistics at the University of Washington and member of the panel, told the Globe that Biogen was like a Texas sharpshooter who fires a shot at a barn and “then draws a target around the bullet hole.”

Knopman did not participate in the committee meeting for the Biogen drug because he was an investigator for one of the trials. But he was quoted during the meeting by Michael Carome, director Public Citizen’s Health Research Group, saying any evidence that the drug works “is terribly weak.”

So why did the FDA approve the drug?

On Monday, the FDA brushed aside the concerns from its advisory panel, approving the first new medicine for Alzheimer’s disease since 2003.

Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, acknowledged in the agency’s decision letter that the agency knew the advisory panel “did not agree that it was reasonable to consider the clinical benefit of the one successful trial as the primary evidence supporting approval.” Cavazzoni said the agency determined the drug was “reasonably likely” to benefit patients, so it was approved under the “Accelerated Approval Program,” which allows the agency to clear drugs even if there is uncertainty about whether they work.

As a condition of approval, Biogen was asked to conduct a larger clinical trial to show that the drug’s effect — removing a sticky plaque that builds up inside the brain of Alzheimer’s patients — results in benefits to patients. But the timeline of this trial is uncertain, and it could take years.

Does the FDA often disagree with its advisory panels?

Historically, no. A study by national health policy foundation Milbank Memorial Fund found that from 2008 through 2015, the FDA only rebuffed its advisory committee’s recommendation 22 percent of the time. And 75 percent of these disagreements led to a more conservative position from the FDA, unlike the agency’s decision on the Biogen drug.

What else is happening?

Criticism is mounting against Janet Woodcock, the FDA’s acting commissioner, who was named to the position in January by President Joe Biden. She’s been working at the agency for more than 30 years.

Woodcock was part of a similarly controversial FDA decision in 2016 with another Cambridge drugmaker, Sarepta Therapeutics. She voted in favor of approving a therapy for Duchenne muscular dystrophy, despite concern from the agency’s advisory committee, which declined to recommend its approval. Kesselheim was one of the skeptical committee members.

In a tweet on Thursday, Gregg Gonsalves, an assistant professor of epidemiology at Yale University and global health activist, called on Woodcock to resign, citing previous decisions that he said put “industry’s interests above the public health.”

“It is not trivial that three people resigned,” he said in an interview. “It should send shock waves to the White House.”

Three @US_FDA Advisory Committee members have now resigned. It's time for @DrWoodcockFDA to step down. This isn't her first egregious mistake: Avandia, Plan B, Exondys 51, "Pink Viagra." There is a pattern here of putting industry's interests above the public health. RESIGN NOW.

— Gregg Gonsalves (@gregggonsalves) June 10, 2021