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 Medical School who is also director of the Program On Regulation, Therapeutics, And Law at Brigham and Women's Hospital. He said the FDA is greenlighting Aduhelm despite not having enough proof that the drug will help Alzheimer's patients.
The controversial approval could set a precedent in how similar drugs are evaluated in the future, Kesselheim says.
"I think there's a real danger considering this to be a one-off event," he told NPR on Friday.
Approval of Aduhelm, he added, "now sets a precedent for the treatment of future [Alzheimer's Disease] drugs, as well as drug approvals more broadly, and the amount of data they need."
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 the FDA move "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 said 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 alleged that when the advisory committee voted against the drug in November, its members had been given different criteria to consider than the FDA cited in an explanation of its decision.
Kesselheim also wrote that "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 added 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 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 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 noted 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 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 said. 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 said, Alzheimer's and other dementias bring an overall annual cost of more than $600 billion.
Some patient advocates celebrate FDA's move
Others are cheering the FDA's approval, including advocates for patients who are suffering from other debilitating diseases. In their eyes, the FDA's approval is a sign that the agency is willing to listen to their communities. One such response came from the ALS Association.
"We are heartened by the FDA's decision to speed new treatments to people with Alzheimer's and we need them to do the same for people with ALS [amyotrophic lateral sclerosis] immediately," said Neil Thakur, chief mission officer of the ALS Association.
"There are even more promising therapies in the ALS pipeline, such as AMX0035, which has been shown to be safe, slow disease progression and lengthen life," Thakur said. "People with ALS cannot wait for additional clinical trials when there are potential therapies that have demonstrated efficacy and safety."