As physicians and health policy experts debate the merits of Aduhelm, the first new drug approved for Alzheimer’s disease in 18 years, patients want to know: “Will this medication help me—and how much?”
Doctors explaining the pros and cons of Aduhelm won’t have a definitive answer.
“On an individual basis, it will be absolutely impossible to predict,” said Dr. Allan Levey, director of the Goizueta Alzheimer’s Disease Research Center at Emory University.
Cognitive decline varies widely among people who have started experiencing memory and thinking problems or who are in the earliest stage of Alzheimer’s—the patients in whom Aduhelm was tested, Levey noted.
“The nature and rate of progression varies tremendously, and we’re not going to know when we treat somebody [with Aduhelm] if their progression will be fast or slow or average—we just won’t be able to say.”
Nor will it be possible to specify how much difference this drug would make for a given patient.
“To try to tell an individual how much delay in progression they’ll experience [if they take Aduhelm] is simply something we cannot do,” said Dr. Jason Karlawish, a professor at the University of Pennsylvania Perelman School of Medicine and co-director of the Penn Memory Center.
With many unanswered questions about Aduhelm’s approval, the House Committee on Oversight and Reform has opened an investigation. Faced with criticism over insufficient guidance, the FDA on July 8 revised the drug’s label to narrow its potential use.
“Treatment with ADUHELM should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials,” it now reads.
These developments make the job of educating patients and families about Aduhelm and recommending for or against it extraordinarily difficult for physicians.
Conversations are going to be “very challenging, given the complexity of the information that needs to be conveyed.” Karlawish said.
Here are key points that experts aim to explain.
Although data from two Aduhelm clinical trials were inconsistent, the FDA granted accelerated approval to the drug noting it was “reasonably likely to result in clinical benefit.” But this is speculative, not a proven result.
He characterized positive results from one clinical trial of Aduhelm as “a tiny clinical change.” On an 18-point scale used to evaluate cognition and functioning, patients who responded to the drug experienced a 0.39 slowing in the rate of decline over 18 months. Roughly, this translates into a four-month delay in subtle symptoms.
Neuropsychological tests to evaluate cognition typically ask patients to copy a diagram, subtract 7 from 100 and spell a word backward, among other tasks.
“But navigating your daily life is much more complicated, and it’s not at all clear whether Aduhelm’s purported benefit would be enough to impact an individual’s daily living,” said Dr. Samuel Gandy, a professor of neurology and psychiatry at Mount Sinai’s Icahn School of Medicine in New York City.
“The expectation has to be that disease progression will continue,” Emory’s Levey agreed.
The FDA recommends that patients taking Aduhelm get at least three MRI scans of the brain in the first year to check for side effects. Physicians and health systems are discussing what kind of safety protocols are needed beyond these scans.
In clinical practice, only patients who have those deposits should take Aduhelm and imaging to confirm that should be required, experts agreed. But that presents a problem for many patients. Because of their age, most are covered by Medicare, which doesn’t pay for PET imaging outside of research settings. Instead, most medical centers will rely on amyloid cerebrospinal fluid tests, obtained through spinal taps.
“Once you find the APOE4 genotype, all those person’s first-degree relatives are at risk,” Gandy noted, “and you change the psychology of a family immediately.”
The APOE4 gene is linked with a reduced ability to remove plaques from the brain and a higher risk of developing Alzheimer’s.
Add to that the costs for brain scans, monthly infusions, physician services, amyloid tests, and APOE4 genetic testing, and expenses could approach $100,000 a year, some experts suggest.
“The most pressing thing we need is an understanding of payment for this medication,” said Dr. Aaron Ritter, a dementia expert with the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. “Many patients are going to be on a fixed income with limited capacity to pay large amounts.” More than 1,000 patients at the clinic are good candidates for Aduhelm, he noted.
“We are going to start small and go slow until we understand more” about the medication and how patients respond, said Dr. Maria Torroella Carney, chief of geriatrics and palliative medicine at Northwell Health, New York’s largest health care system.
Since Aduhelm wasn’t tested on people with moderate or severe Alzheimer’s, it shouldn’t be given to these patients, several experts said.
“If patients in these later stages ask for the drug, we’ll say we don’t have any evidence that it will work in you and we can’t justifiably give it to you,” said Paulson of the University of Michigan.
“Now that this medication is available, I have to adhere to a core ethic of the practice of medicine, which is respect for patient autonomy,” he said. “If patients and family caregivers ask for Aduhelm after a thorough discussion, I’ll be a reluctant prescriber.”