This post was originally published on this site
July 8: This article was updated to note a change in the F.D.A.’s recommended use for Aduhlem that was announced after it was first published.
Dr. Kenneth Koncilja, a geriatrician at the Cleveland Clinic, saw the announcement from the Food and Drug Administration on June 7, on Twitter: The agency had approved Aduhelm (aducanumab), the first drug to treat Alzheimer’s disease to be approved in nearly 20 years.
The calls from patients’ spouses and family members began within the hour, and have not stopped. “I was shocked at how fast the word spread — ‘Hey, is this something we can use? When can we get it?’” Dr. Koncilja recalled. “There’s a mix of excitement, anxiety and desperation.”
His first call that morning came from Joan Morehouse, 78, who has been caring for her 71-year-old husband, James, in their home in North Perry, Ohio, since his Alzheimer’s diagnosis four years ago. She has watched him get lost on familiar drives and forget their grandchildren’s names.
When her brother and her son both emailed her a news article about the F.D.A. action, she recalled, “I said, ‘Oh, my God, my prayers have been answered.’”
It fell to Dr. Koncilja to explain the complexities: That Aduhelm is not yet widely available. That protocols determining which patients qualify have yet to be developed. That the clinical trial data was ambiguous and that the drug might bring no noticeable improvements in daily life. That its side effects include brain swelling and bleeding.
And that its maker, Biogen, estimates the annual cost of monthly intravenous infusions at $56,000, plus expensive scans and tests.
“It’s a more difficult question than I’ve ever had before,” Dr. Koncilja said. Patients ask him how their lives will change, “and I don’t know how to answer.”
In the weeks since the F.D.A.’s action, which initially placed virtually no restrictions on prescribing the drug, geriatricians, neurologists and other doctors across the country have been fielding similar questions.
Aduhelm has generated intense controversy. Biogen stopped two trials in 2019 because they demonstrated no benefit, then submitted an F.D.A. application after a later analysis of one trial showed slightly slower cognitive decline at high doses.
In a letter to the F.D.A., the American Geriatrics Society argued that approval was “premature given the lack of sufficient evidence.” The Society for Post-Acute and Long-Term Care Medicine later came to a similar conclusion.
The F.D.A.’s own advisory committee strongly recommended against approval, and three member scientists resigned in protest when the agency overrode its advice. A new survey of 200 neurologists and primary care doctors has found that most disagreed with the F.D.A. decision.
Senators Elizabeth Warren, Democrat of Massachusetts, and Bill Cassidy, Republican of Louisiana, have called for a hearing, concerned that spending billions on Aduhelm could undermine Medicare. The House Committee on Oversight and Reform has announced an investigation into the drug’s approval and pricing.
On Thursday, reacting to widespread criticism, the F.D.A. narrowed the drug’s recommended use to those with mild cognitive impairment or mild Alzheimer’s disease, noting that there was no data on its safety or effectiveness in later stages of dementia.
Given all that, should older adults consider Aduhelm? “The F.D.A. has passed the determination along to the American family,” said Dr. Jason Karlawish, co-director of the Penn Memory Center, who, with a number of other doctors, publicly opposed the drug’s approval.
Penn Memory doctors are receiving anxious inquiries, too. Geeta Simons, a musician in Philadelphia whose 80-year-old father has Alzheimer’s, messaged her father’s neurologist there. “I wanted to believe that this was that magical save,” she said.
Such doctors face “a dilemma,” Dr. Karlawish said, “a moment when there’s no decision that resolves all the uncertainties and settles the ethical concerns.”
“It puts us in a bad place,” agreed Dr. Karina Bishop, a geriatrician at the University of Nebraska Medical Center. Ethically, she added, “if this drug was available right now, I would not feel able to prescribe it.”
Even as individual doctors grapple with advising patients, hospitals and health systems are devising protocols for when Aduhelm becomes more widely available, probably within weeks.
At the Mayo Clinic, said Dr. Ronald Petersen, a neurologist who directs the Alzheimer’s Disease Research Center there, “we’re going to stick pretty close to the inclusion and exclusion criteria used in the trial.”
That means only patients with mild cognitive impairment or early Alzheimer’s disease would qualify, after an M.R.I. to rule out certain conditions and risks, and a P.E.T. scan or lumbar puncture to confirm the presence of amyloid. The Mayo protocols, like the clinical trials, would exclude people taking blood thinners like Warfarin or Eliquis.
“It’s not like you come in and say, ‘I’m a little forgetful,’ and we say, ‘Here’s this drug,’” said Dr. Petersen. But not every provider, he acknowledged, will employ such safeguards.
Dr. 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 monitoring, it would be the first time in medicine that was ever done.”
He pointed out another consequence of 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. Intended to demonstrate public support for approval of aducanumab, the effort included newspaper ads and social media posts.
Now Dr. Widera, who has worked with a local chapter to train medical students and residents, is seeking an alternate source of information to which to refer patients. He has come to mistrust the Alzheimer’s Association, calling it “a big promoter, almost a marketer, for Biogen,” which, like other pharmaceutical firms, helps underwrite the organization and contributed $275,000 to it last year.
The association said in an email that “history has shown us that approvals of the first drug in a new category will invigorate the field, increase investments in new treatments and generate greater innovation.”
One major unpredictable factor in Aduhelm’s future: insurance coverage. Medicare could decide to authorize coverage as “reasonable and necessary,” to deny or limit it, or to delay a decision. A spokesman at the Centers for Medicare and Medicaid Services said it was reviewing the F.D.A.’s decision and would have more information soon.
Given the drug’s announced price tag, a restrictive Medicare policy could put it beyond reach for most older Americans.
Eventually, the F.D.A. might also take action against Aduhelm. Its “accelerated approval” process requires Biogen to undertake a new clinical trial; if that shows no benefit, the agency could withdraw 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 wrestling with how to respond.
“One of my core principles is respect for patient autonomy, especially for this disease, which degrades a patient’s ability to exercise self-determination,” said Dr. Karlawish. Slightly softening his published opposition to Aduhelm, he said that he now would prescribe it, after extensive discussions with patients, “but I’d be a reluctant prescriber.”
Several doctors described gently dissuading patients by noting the uncertainty that the drug would help, the potentially disabling side effects and the many unknowns. “They have been open to waiting and getting more information,” Dr. Bishop said.
Ms. Morehouse, for instance, had heard nothing about Aduhelm before the F.D.A. acted. “We are on a horrible journey,” she said of her husband and herself. Perhaps with the new drug, “we could have maybe not a normal life, but a better life.”
During their phone call, she listened as Dr. Koncilja noted that the science was exciting but that Aduhelm was no miracle drug. She heard for the first time about brain swelling or bleeding, “and that scared me,” she said. “Would I ever want to put Jim through that?” She was staggered by the price, which she cannot pay.
Her excitement has abated. “But Dr. Koncilja didn’t take away all my hope,” she said. “He told me, ‘Let’s see the potential through the summer, and we’ll confer again in the fall.’”