After much controversy, more resignations in protest against the FDA accelerated approval of Biogen’s Alzheimer’s drug Aduhelm (aducanumab), which is administered by infusion. Here's some context on what the drug is, who it's for, and why so many people resigned around its approval.
In a bold act of protest against FDA approval of Biogen’s new infusion-based Alzheimer’s treatment Aduhelm, a total of three members of an independent advisory committee advising the FDA on the drug have now resigned.
“This might be the worst approval decision that the F.D.A. has made that I can remember,” said Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, told the New York Times. Dr Kesselheim submitted his resignation on Thursday after sitting on the committee for six years, according to the report.
Two other members of the committee resigned earlier this week, after the committee overwhelmingly rejected the approval in November, stating the clinical data didn’t support the decision to approve the drug.
Since the drug’s approval, controversy around its clinical trials’ ambiguous data has continued, and new confusion has arisen. One issue: Questions are swirling around the FDA’s drug label, which indicates the drug is applicable for a much larger audience than were tested in the drug’s clinical trials, leaving experts asking: Who is Aduhelm really for?
Who should take Aduhelm?
The drug was designed to clear beta-amyloid plaque that accumulates in the brain — a key hallmark of Alzheimer’s. The trials specifically tested effectiveness — and safety — on participants in the earliest stages of Alzheimer’s disease, with the mildest symptoms.
However, there appears to be a consensus among experts that the drug’s label, published by the FDA with the drug’s approval, is alarmingly broad — that it indicates no restrictions to certain categories of Alzheimer’s patients, despite the narrower focus of the trials. Instead, the label implies the drug is appropriate for anyone with Alzheimer’s disease, at any stage. (The FDA did not respond to a request for comment in time for the publication of this story.)
Dr. Stephen Salloway, a principal investigator of the aducanumab clinical trial and the director of Butler Hospital’s Memory and Aging Program, is one researcher concerned by the broadness of the FDA’s current language on the Aduhelm label.
“I was hoping, if there was an approval, there’d be a more narrow label that mirrored the trial because the only evidence we have is from the trial,” Salloway, who has consulted for Biogen and other pharmaceutical companies, told Being Patient in response to the news of the approval.
“There’s really no evidence that it works for later stage disease,” he said, “and it probably doesn’t work for later stage disease, because based on the biology of what we know about Alzheimer’s, the amyloid process pretty much peaks during the earlier stage.”
Other issues include the expected high costs of Aduhelm for patients, and the ambiguity around duration limit.
How long should you take Aduhelm?
Aduhelm is administered via a monthly IV infusion. Another point of confusion is that the drug, which comes with a staggeringly high price tag — approximately $56,000 per year plus associated costs, like neurological consults and FDA-required periodic MRIs — hasn’t been tested long enough to determine how long patients need to take it in order for its benefits to stick, and the FDA did not place a limit on treatment duration.
Lack of a duration limit on the FDA’s label suggests people could stay on Aduhelm until either all the beta-amyloid plaque appears to be removed from the brain, or their Alzheimer’s progresses.
But there is still much unknown about the treatment: Do its effects wane over time? Do they persist as long as a person is on the drug, meaning that the course of prescription is lifelong? Or will patients be able to stop taking it eventually without the beta-amyloid plaques (the Alzheimer’s hallmark the drug is designed to fight off) returning?
When asked if people need to stay on Aduhelm for life, Salloway told Being Patient it is still an open question.
“We know that amyloid lowering does take place after a year and 18 months, and it continues up to a certain point,” he said. “But we don’t know how long someone really needs to get those monthly infusions. If they get to a point where they’re considered amyloid negative, or they don’t look like they have Alzheimer’s on the PET scan, is that a good time to stop?”
Can anyone with Alzheimer’s get an Aduhelm prescription?
Even with more restrictive or specific labeling, care providers anticipate it will be hard for those with prescribing power to “hold back the flow of requests,” as one neurologist put it to STAT News.
That said, many neurologists are worried that many of the healthcare providers who will be called upon to prescribe Aduhelm will not have specialized experience in Alzheimer’s or dementia.
Experts have also expressed concern that doctors with the power to prescribe the drug may not be aware that this drug was only tested on people at the earliest stage of the disease, with the mildest symptoms. But neurologist Babak Tousi of the Cleveland Clinic is among those who hope industry “gatekeepers” will help narrow down the prospective patient pool in a way the FDA label has not.
Tousi, previously an aducanumab trial investigator and paid Biogen consultant, told STAT: “Even if [the FDA] allows it, we will be dealing with insurers and other gatekeepers” who will try to restrict Aduhelm to early-stage patients. “This is a medication for the right patient,” he said, “and the right patient in our mind is someone who is in early stages of the condition.”
Neurologist Jeff Gelblum at First Choice Neurology agrees: “This is not a free-for-all where everybody’s grandmother is going to take this drug,” he told FiercePharma. “It’s going to have to be for a defined patient population who meet the parameters for inclusion.”
Ultimately, people with dementia should to consult with a neurologist or a clinician with a specialization in Alzheimer’s or dementia to understand whether Aduhelm is right for them.