As doctors and health policy experts debate the merits of Aduhelm, the first Alzheimer’s drug approved in 18 years, patients simply want to know: “Will it help me?”
Doctors do not have a definitive answer. “In each person, 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 begun to experience memory and thinking problems, or who are in the earliest stage of Alzheimer’s, the patients Aduhelm was evaluated in, Levey said.
“The nature and speed of progression vary enormously, and we won’t know when treating someone [with Aduhelm] if their progression will be fast, slow, or average; We just won’t be able to tell, ”Levey explained.
Nor will it be possible to specify the difference that this drug would make for a given patient. “Trying to tell a person how much delay in progression they will experience [if they take Aduhelm] is just something we can’t do,” said Dr. Jason Karlawish, professor at the Perelman School of Medicine at the University of Pennsylvania and co-director of the Penn Memory Center.
The uncertainty about the potential benefits of Aduhelm, which received conditional approval from the Food and Drug Administration (FDA) on June 7, is considerable. A phase 3 drug trial found that a high dose taken over 18 months delayed cognitive decline by approximately four months; a second clinical trial showed no effect.
The FDA is requiring drug makers Biogen and Eisai Inc. to conduct a post-approval trial to provide more data, but final results may not be available until February 2030.
With many unanswered questions about Aduhelm’s passage, the House Oversight and Reform Committee has opened an investigation. Faced with criticism for insufficient guidance, the FDA modified the drug’s label to limit its potential use.
Now it says: “Treatment with ADUHELM should be started in patients with mild cognitive impairment or in mild dementia stage of the disease, the population in which the treatment was tested in clinical trials.”
These changes make the job of educating patients and their families about Aduhelm and recommending it for or against it extraordinarily difficult for clinicians.
The talks will be “very challenging, given the complexity of the information that needs to be conveyed,” Karlawish said.
These are the key points that the experts should explain:
Efficacy has not been proven. Aduhelm has been shown to be very effective in removing beta-amyloid protein, a hallmark of Alzheimer’s, from the brains of patients. Clusters of this protein, known as amyloid plaques, are believed to be related to the underlying development of the disease. But clinical trials of other drugs that kill amyloid plaques have not shown efficacy in stopping the progression of Alzheimer’s.
Although data from two Aduhelm clinical trials were inconsistent, the FDA granted expedited approval to the drug, noting that it was “reasonably likely to produce a clinical benefit.” But this is speculative, not a proven result.
The potential benefits are small. Dr. G. Caleb Alexander, co-director of the Johns Hopkins Center for Drug Safety and Efficacy, was part of the FDA advisory committee that reviewed Aduhelm, a group that recommended not approving it.
Alexander characterized the positive results of an Aduhelm clinical trial as “a small clinical change.” On an 18-point scale used to assess cognition and functioning, patients who responded to the drug experienced a 0.39 slowdown in the rate of decline over 18 months.
This translates into approximately a four-month delay in subtle symptoms.
Neuropsychological tests to assess cognition often ask patients to copy a diagram, subtract 7 from 100, and spell a word backwards, among other tasks. “But navigating their daily life is much more complicated, and it is not entirely clear whether the supposed benefit of Aduhelm would be enough to affect a person’s daily life,” said Dr. Samuel Gandy, professor of neurology and psychiatry at the School. Mount Sinai Icahn of Medicine in New York City.
The progression of the disease will continue. Suppose someone has a cognitive impairment or other functional impairment and decides to take Aduhelm. Will they return to normal? There is no evidence that this happens, ”said Dr. Henry Paulson, professor of neurology and director of the Michigan Alzheimer’s Disease Center.
“The expectation should be that the progression of the disease continues,” agreed Emory’s Levey.
Possible side effects are common. 41% of patients treated with the highest dose of Aduhlem (10 mg), the subgroup that showed some response in a clinical trial, had brain bleeds and swelling, according to a document published by the FDA. Brain scans identified them as mild in 30% of cases, moderate in 58%, and severe in 13%. Most cases were resolved, without serious incident, within three months.
The FDA recommends that patients taking Aduhelm have at least three MRIs of the brain during the first year to check for side effects.
Other tests will be necessary. Aduhelm was tested in patients with beta-amyloid deposits in the brain that had been confirmed by positron emission tomography (PET) brain imaging.
In clinical practice, only patients who have such deposits should take Aduhelm and obtain images to confirm that they should be needed, the experts agreed. But that presents a problem for many patients. Due to their age, most are covered by Medicare, which does not pay for PET images outside of research settings. Instead, most medical centers will rely on amyloid cerebrospinal fluid tests, obtained using lumbar punctures.
Genetic testing for a form of the apolipoprotein E gene known as APOE4 , the presence of which increases the risk of Alzheimer’s, will likely also be ordered, Gandy suggested.
Patients were more likely to respond to Aduhelm if they carried an APOE4 gene; at the same time, they were more likely to suffer from brain hemorrhage and swelling, he noted. But Medicare doesn’t pay for APOE4 testing and related counseling, and a positive test could significantly affect patients’ families.
“Once you find the APOE4 genotype, all of that person’s first degree relatives are at risk,” Gandy noted, “and you change the psychology of a family immediately.”
Therapy will be expensive. Medicare and private insurers have yet to decide whether to place restrictions on who can get coverage for Aduhelm, which will be administered through monthly infusions at medical centers. Considering an annual list price of $ 56,000 for the drug alone, KFF researchers estimate that some Medicare beneficiaries could pay up to $ 11,500 out of pocket to cover their coinsurance.
Add to that the costs of brain scans, monthly infusions, medical services, amyloid tests and APOE4 genetic testing, and the expenses could approach $ 100,000 a year, experts suggest.
“The most urgent thing we need is to understand paying for this drug,” said Dr. Aaron Ritter, a dementia expert at the Lou Ruvo Center of the Cleveland Clinic for Brain Health in Las Vegas. “Many patients will have fixed incomes with limited ability to pay large amounts.” More than 1,000 patients at the clinic are good candidates for Aduhelm, he added.
Specialists will not prescribe it for all Alzheimer’s patients. Although doctors can prescribe an approved drug to whom they think will help, dementia experts say Aduhelm should be considered only for patients similar to those in clinical trials: individuals with mild cognitive impairment (memory and thinking problems that do not interfere with their functioning) and with early-stage Alzheimer’s disease (when symptoms are still mild but functioning begins to deteriorate).
“We’re going to start small and go slow until we understand more” about 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. York.
Since Aduhelm was not tested in people with moderate or severe Alzheimer’s, it should not be given to these patients, several experts said. “If patients in these later stages request the drug, we will say that we have no evidence that it works for them and that we cannot justifiably give it to them,” said Paulson of the University of Michigan.
Doctors will respect the wishes of patients. Even doctors who are concerned that Aduhelm’s potential harms may outweigh the potential benefits said they will prescribe the drug with caution and careful consideration. Karlawish of the University of Pennsylvania is among them.
“Now that this medicine is available, I have to follow a fundamental ethic of the practice of medicine, which is respect for the autonomy of the patient,” he said. “If patients and family caregivers ask for Aduhelm after extensive discussion, I will be a reluctant prescriber.”
This article was originally posted on Doctors weigh pros and cons of prescribing new Alzheimer’s drug