At the Washington University School of Medicine in St. Louis, the phone lines were “blowing up” Monday.
Alzheimer's disease patients and family members were calling about Biogen and Eisai's Aduhelm, approved just hours before, asking whether they could get on a list for treatment, said Erik Musiek, M.D., associate professor of neurology.
It was a similar scene in Florida, where neurologist Jeff Gelblum, M.D., at First Choice Neurology answered calls “non-stop,” and in Los Angeles at Cedars-Sinai Medical Hospital where memory and geriatric medicine specialist Zaldy Tan, M.D., said many people expressed interest—including some international patients willing to fly in to get it.
While high patient demand for the first Alzheimer's drug approved in 18 years is likely no surprise, what may be less anticipated is that doctors are ready to prescribe it—despite debatable clinical trial results that have some experts still advising against it.
So why would most physicians plow ahead? Because the reality in the neurology, gerontology and even primary care practices where Alzheimer’s patients are treated is that Aduhelm is the now the only drug approved to target the underlying disease process.
“It would be nice to have firm clinical data that it worked instead of the muddled message in the clinical trial,” Musiek said. “But I think even the most firm opponents—maybe not all of them—would probably agree there is some encouraging signal in that data and enough of it that a lot of clinicians will prescribe it.”
Some physicians are more positive than others, of course, but overall the inclination to prescribe seems to be a qualified yes. Qualified, meaning that they will prescribe after careful evaluation and tests of patients who are appropriate and might benefit most—and after learning many more details about things like eligibility, cost, administration and ongoing care. Aduhelm is an IV drug dosed every four weeks with a list price of $56,000.
Tan said the approval represents a "hope that people have been waiting for a long time, but as you know, it’s not a simple stat. There are still many unknowns about what is the eligibility, will there be capacity for infusion, what are the costs, what are the insurance requirements, what are the monitoring requirements … and how are we logistically going to handle the demand for this medication?”
Tan acknowledged there seems to be a split on Aduhelm between academic scientists who are more hesitant on the scientific data and doctors in private practice who are more ready to prescribe.
Gelblum, speaking late Monday afternoon and with 25 patient calls still to return about the approval, was optimistic.
“What we now have before us on June 7, 2021, is for the first time in 20 years we’ve got a new drug that actually addresses the amyloid plaque,” he said.
Gelblum agreed that the FDA approval and clinical data were “not a slam dunk by any stretch of the imagination” and that there are still a lot of questions to be answered and qualifications to be made about who can, and should, get the drug. Still, he believes there is a group that can benefit and that Aduhelm marks the beginning of more Alzheimer's drugs.
“This is not a free-for-all where everybody’s grandmother is going to take this drug. It’s going to have to be for a defined patient population who meet the parameters for inclusion,” he said.
One issue is monitoring. Some clinical trial patients developed Amyloid Related Imaging Abnormalities (ARIA), which involves swelling in the brain. Clinical neurologist Cara Leahy, director of cognitive disorders at Memorial Healthcare in Michigan, said she’ll want to ensure patients are at low risk for that. Aduhelm will come with a warning about the condition and additional MRIs will be required for monitoring.
Another neurologist B. Joy Snider, who is also a professor at Washington University School of Medicine and directs its clinical trial unit at its Knight Alzheimer’s Disease Research Center where Biogen’s Engage and Embark studies were done, pushed some responsibility back to the FDA .
The federal agency will need to provide clear guidance because “many of the people who will likely be called upon to prescribe this drug will be neurologists who do not have specialized training in dementia or a lot of experience in dementia.”
Snider also recognized the hope and excitement around Aduhelm, but pointed out that it’s also “anxiety-provoking for both providers and their patients and their families because there’s a whole of unknowns.”
She and the clinic staff are asking people to be patient while the FDA works out more guidance and “we figure out how this is going to work.”
One big question for doctors who are considering prescribing Aduhelm is the patient audience. While Biogen trials only included early-stage Alzheimer’s patients, the FDA approved the drug for all patients.
That may serve as a cutoff point even for doctors who are willing to prescribe.
"We have been operating under the assumption that the eligibility criteria would mimic the entry criteria for the clinical trial, which is very mild symptoms with a relatively good MMSE score," Musiek said, referring to a common Alzheimer's assessment tool. "[I]t would not make sense to me to use it in more severe disease at this point."
Leahy agreed that patients who mirror those included in the late-stage studies will be priority. But identifying mild Alzheimer’s patients best suited for Aduhelm, rather than those with severe disease, will be a hurdle out the gate, she added.
Analysts expect doctors will prescribe Aduhelm now that it's approved, posting up lofty sales estimates Monday—as high as $10 billion at peak. Cantor Fitzgerald analysts wrote Biogen is "set up for one of the biggest drug launches in biopharma history," with its peak sales prediction of $8.2 billion in 2028.
However, physicians and analysts aren’t the only factors in the drug's uptake. Insurers will put up hurdles to the $56,000 drug—they'll likely cover it but are expected to set strict criteria to limit how broadly, perhaps by adhering closely to the characteristics of the clinical trial population rather than the FDA's "shockingly broad" label, as one analyst put it.
Then there's the practical matter of administration: Only about 900 medical centers are able to treat at launch. Those are key considerations in what is expected to be a long runway toward establishing Aduhelm use in practice.
And of course, not all clinicians and researchers agree with the FDA nod for use with any group of patients.
An FDA approval doesn’t change the facts of the clinical trials, Vanderbilt University Medical Center professor Matthew Schrag, M.D., Ph.D., said in an email to Fierce Pharma.
He ticked off three of those: Neither of Biogen’s phase 3 trials completed; the potential benefits are small and come at a high price; and the risks are high, with one-third of patients having developed swelling in the brain.
“Importantly, this approval requires Biogen to conduct a new trial,” he said. “For the safety of our patients, until more data is available, we should proceed with great caution.”
Jason Karlawish, M.D., a professor of medicine and medical ethics at the University of Pennsylvania, said he won’t prescribe it in an opinion column in Stat last week.
He followed up Monday on Twitter, posting, “Desperation should drive funding science—and for #Alzheimers that means lot$ & lot$ of dollars—but desperation should not drive the interpretation of the results of that science.”
The Institute for Clinical and Economic Review also weighed in with a scathing assessment of the approval, saying it believes the “FDA failed in its responsibility to protect patients and families from unproven treatments with known harms.”
Yet, for many patients and their families suffering with the day-to-day burden of Alzheimer’s, differing scientific opinions aren’t likely to matter. And in the end, that’s the group physicians will make their decisions for.
“Most people who have a diagnosis of Alzheimer’s are thinking about now; they’re not worried about a few years down the road. It’s hard to think in an objective way when you’re in that situation,” Musiek said, adding, “There are certainly reservations neurologists have about it, but I think most will still prescribe it.”
Despite Aduhelm’s imperfections, the hope is that it marks the beginning of a new wave of Alzheimer’s medication—Leahy predicted current patients really want to “be a part of something that might help generations from now.”
Editor's note: Noah Higgins-Dunn and Fraiser Kansteiner contributed reporting for this story. This story has also been updated with additional comments from physicians.