3 experts quit FDA committee on Alzheimer’s drug approval
Updated June 11, 2021, 7:04 p.m. ET
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 everyone on the panel.
The drug – its generic name is aducanumab – was approved on Monday, triggering a variety of responses, ranging from celebrations among some patients, caregivers and doctors to pointed questions about the drug’s benefits and costs.
The latest outing comes from Dr Aaron Kesselheim, professor at Harvard Medical School and also director of the Regulatory, Therapeutics and Law program at Brigham and Women’s Hospital. He said the FDA was giving Aduhelm the green light despite not having enough evidence that the drug would help Alzheimer’s patients.
The controversial approval could set a precedent in how similar drugs will be evaluated in the future, Kesselheim says.
“I think there is a real danger in considering this to be a one-time event,” he told NPR on Friday.
Aduhelm’s approval, he added, “now sets a precedent for the treatment of future [Alzheimer’s Disease] drugs, as well as drug approvals in general, and the amount of data they need.
Doctor sends scathing resignation letter to FDA
“Fast Track Approval isn’t meant to be the backup you use when your clinical trial data isn’t good enough for regular approval,” Kesselheim said via Twitter Monday as the FDA issued its approval for Aduhelm.
Kesselheim called the FDA decision “possibly the worst drug approval decision in recent US history” in a scathing resignation letter he sent to the acting commissioner of the FDA on Thursday, Janet Woodcock.
“It is clear to me that the FDA is not currently able to adequately incorporate the committee’s scientific recommendations into its approval decisions,” wrote Kesselheim, who had served on the FDA’s advisory committee since 2015.
He said the FDA changed its approach to Aduhelm at the last minute to grant fast-track approval – a classification that will require manufacturers of the drug 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 were given different criteria to consider that the FDA cited in an explanation of its decision.
Kesselheim also wrote that “some of the questions the FDA asked to be answered were worded in a manner that seemed biased to provide answers that would promote drug approval.”
Still, 10 of the 11 committee members voted against approving the drug, according to medical news site STAT, which added that the latest member had voted “uncertain.”
The FDA has acknowledged the controversy and attention generated by the drug’s approval. The agency “concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy,” said Patrizia Cavazzoni, director of the Center for Drug Evaluation and Research at the FDA, in a statement this week.
In resigning, Kesselheim joins neurologists David Knopman of the Mayo Clinic in Minnesota and Joel Perlmutter of the University of Washington in St. Louis, who this week announced their departure from the central and peripheral nervous system drugs advisory committee of the FDA.
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 reported:
“This drug has generated all kinds of enthusiasm because it is the first approved drug that does more than just relieve symptoms of Alzheimer’s disease. 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 help patients avoid memory loss and thinking problems. A large study has shown this to be the case. Another showed no.
He noted that the FDA would not normally be expected to grant approval for a drug under the mix of circumstances that surrounded Aduhelm.
Make connections with another expensive drug
In his resignation letter, Kesselheim also cited the late 2016 FDA approval of eteplirsen, which is intended 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 very problematic drugs” that may not help people with terrible diseases, Kesselheim warned, “will undermine the care of these patients, the public’s confidence in the FDA, the pursuit of useful therapeutic innovations and the affordability of the health system. “
Aduhelm was developed by the American company Biogen and the Japanese company Eisai. When the drug hits the market, it will be extremely expensive.
The drug will be given by infusion every four weeks, which will cost about $ 56,000 annually, the companies said. This is the list price, which does not necessarily reflect the out-of-pocket expenses for someone with insurance and / or Medicare. Preliminary estimates suggest that patients’ co-pay for the drug could cost around $ 11,500 per year.
To defend this high cost, Biogen and Eisai point to the huge sums of money needed to care for someone with Alzheimer’s disease. Each year in the United States, they said, Alzheimer’s disease and other dementias result in an overall annual cost of over $ 600 billion.
Some Patient Advocates Celebrate FDA Decision
Others applaud the FDA’s approval, including advocates for patients with other debilitating illnesses. They see the FDA’s approval as a sign that the agency is ready to listen to their communities. One of those answers came from the ALS Association.
“We are encouraged by the FDA’s decision to speed up new treatments for people with Alzheimer’s disease and we need them to do the same for people with ALS. [amyotrophic lateral sclerosis] immediately, ”said Neil Thakur, Head of Mission of the ALS Association.
“There are even more promising therapies in the ALS pipeline, such as AMX0035, which has been shown to be safe, slows disease progression and prolongs life,” Thakur said. “People with ALS cannot wait for further clinical trials when there are potential therapies that have been shown to be effective and safe.”