Kenneth Koncilja, a geriatrician at the Cleveland Clinic, saw the US Food and Drug Administration (FDA) announcement on Twitter on June 7: the agency had approved Aduhelm (aducanumab), the first drug to treat Alzheimer’s disease being approved in nearly 20 years.
The calls from the spouses and relatives of the patients began an hour following the announcement and have not stopped.
“I was surprised how quickly the word got out: ‘Hey, can we use it? When can we get it?” Koncilja recalled. “There is a mix of excitement, anxiety and despair.”
The first call she received that morning was from Joan Morehouse, 78, who has been caring for her husband James, 71, at their North Perry, Ohio, home since he was diagnosed with Alzheimer’s four years ago. She has seen him get lost on family journeys and forget the names of his grandchildren.
Morehouse recalled that when her brother and son emailed her an article regarding the FDA action, she thought, “My God, my prayers have been answered.”
It fell to Koncilja to explain the intricacies: that the Aduhelm drug is not yet available; that the protocols that determine which patients qualify have not yet been developed; that the data from clinical trials are equivocal and that the drug is not likely to bring noticeable improvements in daily life; In addition to its side effects are inflammation and brain hemorrhage.
Also, its manufacturer, Biogen, estimates the annual cost of monthly intravenous infusions at $56,000, plus expensive CT scans and tests.
“It’s one of the hardest questions I’ve ever been asked,” Koncilja said. Patients ask her how their lives will change, to which she comments, “And I don’t know what to say.”
In the weeks since the FDA’s decision, which places virtually no prescribing reservations for the drug, geriatricians, neurologists and other physicians across the United States have responded to similar questions.
Aduhelm has generated intense controversy. Biogen stopped two trials in 2019 because they failed to show any benefit, and then filed an application with the FDA following a subsequent analysis of one trial showed slightly slower cognitive decline at high doses.
In a letter to the FDA, the American Geriatrics Society argued that the approval was “premature given the lack of sufficient evidence.” Later, the Society for Long-Term and Aftercare Medicine came to a similar conclusion.
The FDA’s own advisory committee strongly recommended once morest approval, and three member scientists resigned in protest when the agency ignored their advice. A new survey of 200 neurologists and primary care physicians has revealed that the majority disagree with the FDA’s decision.
Democratic Sen. Elizabeth Warren of Massachusetts and Republican Sen. Bill Cassidy of Louisiana have requested a hearing, out of concern that spending billions of dollars on Aduhelm might hurt Medicare. The House Committee on Oversight and Reform announced an investigation into the drug’s approval and pricing.
Given all this, should older adults consider taking Aduhelm?
“The FDA has moved the determination to the American family,” said Jason Karlawish, co-director of the Penn Memory Center, who, along with other doctors, publicly opposed approval of the drug.
Doctors at Penn Memory are also taking inquiries from concerned people. Geeta Simons, a Philadelphia musician whose 80-year-old father has Alzheimer’s, sent a message to her father’s neurologist at the center.
I wanted to believe that this was magical salvation,” he said.
These doctors are faced with “a dilemma,” Karlawish said, “a time when there is no decision that resolves all the uncertainties and settles the ethical questions.”
“It puts us in a quandary,” said Karina Bishop, a geriatrician at the University of Nebraska Medical Center. From an ethical standpoint, she said, “If this drug were available right now, I wouldn’t feel able to prescribe it.”
Even as doctors scramble to advise patients, hospitals and healthcare systems are devising protocols for when Aduhelm is available, perhaps weeks from now.
At the Mayo Clinic, said Ronald Petersen, a neurologist who directs the Alzheimer’s Disease Research Center, “we’re going to be pretty close to the inclusion and exclusion criteria used in the trial.”
That means only patients with mild cognitive impairment or early-stage Alzheimer’s disease would qualify, following an MRI to rule out certain conditions and risks, as well as a positron emission tomography (PET) scan. ) or a lumbar puncture to confirm the presence of amyloid. The Mayo Clinic protocols, like clinical trials, would exclude people taking blood thinners such as Warfarin or Eliquis.
“It’s not like you come in and say, ‘I’m a little forgetful,’ and we’re like, ‘Take this medication,’” Petersen said.
However, he acknowledged that not all providers will use these security measures.
Eric Widera, a geriatrician at the University of California, San Francisco, expressed a similar concern: “If doctors were extremely cautious and limited this drug to the very specific population included in the study, with very careful follow-up, it would be the first time to do that in medicine”.
He pointed to another consequence of the federal approval: a rift between some doctors and the Alzheimer’s Association, the national advocacy group, which this spring mounted a campaign it called More Time. The campaign, which was intended to demonstrate public support for the approval of aducanumab, included posts in newspapers and on social media.
Now Widera, who has worked with a local chapter to train medical students and residents, is looking for an alternative source of information to which he can refer patients. She has come to distrust the Alzheimer’s Association, calling it “a big promoter, almost a marketer, of Biogen,” which, like other pharmaceutical companies, helps fund the organization, giving it $275,000 last year.
The association said in an email: “History has shown us that the approval of the first drug in a new category invigorates the field, increases investments in new treatments and generates greater innovation.”
A major unpredictable factor in Aduhelm’s future is insurance coverage. Medicare might decide to allow coverage as “reasonable and necessary,” deny or limit it, or delay the decision. A spokesman for the Centers for Medicare and Medicaid Services said he was reviewing the FDA’s decision and would have more information soon.
Given the drug’s advertised price, a restrictive Medicare policy might put it out of reach for most older Americans.
In time, the FDA might also take action once morest Aduhelm. Its “expedited approval” process requires Biogen to conduct a new clinical trial; if it doesn’t show any benefit, the agency might withdraw the approval, but Biogen has until 2030 to report those results; by then, thousands of hopeful patients might already be taking Aduhelm.
For now, doctors are debating how to respond
“One of my fundamental principles is respect for the autonomy of the patient, especially in the case of this disease, which degrades their capacity for self-determination,” Karlawish commented. He softened some of his opposition to Aduhelm, saying he would now prescribe it, following extensive discussions with patients, “but he would do so reluctantly.”
Joan and James Morehouse, who have been awaiting treatment for Alzheimer’s since James’ diagnosis four years ago, in North Perry, Ohio, on June 26, 2021. (Amber Ford/The New York Times)
A photograph of Joan and James Morehouse, taken before James was diagnosed with Alzheimer’s, in North Perry, Ohio, on June 26, 2021. (Amber Ford/The New York Times)
