Three experts have now resigned from a Food and Drug Administration advisory committee, after the agency approved an Alzheimer’s drug called Aduhelm against the wishes of nearly every member on the panel.
The drug — its generic name is aducanumab — was approved on Monday, setting off a variety of responses, from celebrations among some patients, caregivers and doctors to pointed questions about the drug’s benefits and costs.
The latest exit comes from Dr. Aaron Kesselheim, a professor at Harvard’s medical school who is also director of the Program On Regulation, Therapeutics, And Law at Brigham and Women’s Hospital. He says the FDA is green-lighting Aduhelm despite not having enough proof that the drug will help Alzheimer’s patients.
A doctor sends a scathing resignation letter to the FDA
“Accelerated Approval is not supposed to be the backup that you use when your clinical trial data are not good enough for regular approval,” Kesselheim said via Twitter on Monday, as the FDA issued its OK for Aduhelm.
Kesselheim called it “probably the worst drug approval decision in recent U.S. history,” in a scathing resignation letter he sent to acting FDA Commissioner Janet Woodcock on Thursday.
“It is clear to me that FDA is not presently capable of adequately integrating the Committee’s scientific recommendations into its approval decisions,” wrote Kesselheim, who had served on the FDA advisory committee since 2015.
He says the FDA switched its approach to Aduhelm at the last minute to grant accelerated approval — a classification that will require the drug’s makers to conduct another study after it is released to the public. And he alleges that when the advisory committee voted against the drug last November, its members had been given different criteria to consider than the FDA cited in an explanation of its decision.
Kesselheim also wrote, “some of the questions FDA asked the Committee to answer were worded in a way that seemed slanted to yield responses that would favor the drug’s approval.”
Still, 10 of the committee’s 11 members voted against the drug’s approval, according to the STAT medical news site, which adds that the final member voted “uncertain.”
The FDA acknowledged the controversy and attention the drug’s approval has garnered. The agency “concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy,” Patrizia Cavazzoni, director of the FDA Center for Drug Evaluation and Research, said in a statement earlier this week.
By resigning, Kesselheim joins neurologists David Knopman of the Mayo Clinic in Minnesota and Joel Perlmutter of Washington University in St. Louis, who announced their departures from the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee earlier this week.
With the three resignations, the federal panel has now lost a third of its members who come from outside the government.
Aduhelm is the first new therapy to be approved for Alzheimer’s disease since 2003.
As NPR’s Jon Hamilton has reported:
“This drug has generated all kinds of excitement because it is the first approved drug that does more than just relieve the symptoms of Alzheimer’s. This drug actually affects an underlying disease process by reducing the amount of sticky amyloid plaque that builds up in the brain. The catch is that removing this plaque may not actually help patients avoid memory loss and thinking problems. One big study showed that it did. Another showed that it didn’t.”
He notes that the FDA would not normally be expected to grant approval to a drug under the mix of circumstances that have surrounded Aduhelm.
Drawing connections to another very expensive drug
In his resignation letter, Kesselheim also cited the FDA’s approval in late 2016 of eteplirsen, which is meant to treat Duchenne muscular dystrophy. The agency’s approach to the two drugs has been a debacle, the doctor said.
Sarepta, the maker of eteplirsen, said at the time that it would charge $300,000 per year for each patient receiving the drug.
The approval of “two highly problematic drugs” that might not help people who are suffering from terrible conditions, Kesselheim warned, “will undermine the care of these patients, public trust in the FDA, the pursuit of useful therapeutic innovation, and the affordability of the health care system.”
Aduhelm was developed by the U.S. company Biogen and the Japanese company Eisai. When the drug hits the market, it will be extremely expensive.
The drug will be administered through infusions every four weeks, resulting in a yearly cost of about $56,000, the companies say. That’s the list price, which doesn’t necessarily reflect the out-of-pocket costs for someone who has insurance and/or Medicare. Preliminary estimates suggest patients’ copayments for the drug could cost around $11,500 annually.
In defense of that high cost, Biogen and Eisai point to the huge amounts of money required to take care of someone with Alzheimer’s disease. Each year in the U.S., they say, Alzheimer’s and other dementias bring an overall annual cost of more than $600 billion.