What Brain Experts Think About the Controversial New Alzheimer’s Drug
The FDA just approved aducanumab, a new drug for Alzheimer's disease. What does it mean for patients? Brain experts weigh in.
Mixed reactions to aducanumab
The recent federal approval of a new drug for Alzheimer’s disease has sparked strong reactions—both for and against—from experts in the field.
Some think the medication, aducanumab, could be a game changer in the long, arduous fight to find effective treatments for Alzheimer’s disease. The approval “ushers in a new era in Alzheimer’s treatment and research,” says Maria C. Carrillo, PhD, chief science officer of the Alzheimer’s Association, in a prepared statement.
But others say aducanumab—which received accelerated approval from the U.S. Food and Drug Administration (FDA) this month—doesn’t have enough evidence to support its use.
“Based on what we currently know, it should not have been approved,” says John Morris, MD, director of the Charles F. and Joanne Knight Alzheimer’s Disease Research Center at the Washington University School of Medicine in Saint Louis, Missouri.
At best, opinions are divided.
“This is inspiring and encouraging, but the concern is whether this is what we actually need,” says Marina Novikova, DO, director of the Center for Cognitive Health at Henry Ford Hospital in Detroit. “What are we getting, practically speaking, from the medication?”
What is Alzheimer’s disease?
Alzheimer’s disease, which affects more than six million Americans, is the most common form of dementia. It’s progressive, meaning it gets worse over time.
Scientists are still unclear about what exactly causes the disease, but one of the hallmarks is the abnormal buildup of proteins, such as amyloid, in the brain.
With no cure and few treatments, the disease is devastating for patients and their families.
“You don’t need any additional support for the idea that this is a miserable disease and it affects many people and it is not currently effectively treated,” Dr. Morris says.
Current treatments for Alzheimer’s disease
Finding effective treatments and even a cure for Alzheimer’s disease is, of course, the holy grail toward which many brain researchers are working, Dr. Morris says.
But Alzheimer’s disease has proven stubbornly resistant, as evidenced by the fact no new drugs have been approved in almost two decades.
The mainstays of therapy only treat symptoms, not the underlying causes.
One, donepezil (Aricept), improves memory a little bit in some people but, in many, does not, explains Joseph Masdeu, MD, PhD, director of the Nantz National Alzheimer’s Center at Houston Methodist and a member of the medical advisory board of Biogen, which makes aducanumab. (Houston Methodist was one of the clinical trial sites for aducanumab.) Aricept also has troublesome side effects.
Another drug, called memantine (Namenda), shows a behavioral benefit in some people but not others, Dr. Masdeu says.
Lecanemab, which was recently approved by the FDA, was reported to result in an extra 6-12 months of an individual being able to drive.
Importantly, adds Joel Salinas, MD, a cognitive-behavioral neurologist at NYU Langone Health in New York City, “none of the medications is shown to clearly change the deterioration of the disease.”
What is aducanumab?
Aducanumab (sold under the brand name Aduhelm) is a different drug entirely. It’s an antibody that binds to amyloid proteins in the brain, leading to reduced levels of protein plaques. The hope is this will alter the underlying course of the disease.
It’s given once a month as an infusion in a clinic or doctor’s office, Dr. Masdeu says.
But clinical trials had inconsistent results.
One suggested the drug could slow the rate of cognitive decline in participants, and one did not. Dr. Morris points out that the clinical benefits seen in one trial were “very small.”
Both trials, however, showed lower levels of amyloid plaques as measured by PET imaging. In granting accelerated approval to aducanumab, Patrizia Cavazzoni, MD, director of the FDA’s Center for Drug Evaluation and Research, said the reduction in amyloid beta plaques “is expected to lead to a reduction in the clinical decline of this devastating form of dementia.”
But that’s far from clear.
Andrew Brookes/Getty Images
What we know about amyloid protein plaques
There’s little doubt that amyloid protein plaques, which glom up the brains of people with Alzheimer’s disease, play a role in the disease. But what is that role?
“We think amyloid beta is central to the causation of Alzheimer’s, but by the time people have developed dementia, it certainly is not amyloid alone. There are many other pathologic processes,” Dr. Morris says.
One of the most consistent things about Alzheimer’s disease is its inconsistency among patients.
“The disease in and of itself can manifest differently from person to person,” says Dr. Salinas.
The heterogeneity of Alzheimer’s disease may explain the inconsistent trial results, says Gayatri Devi, MD, a neurologist specializing in memory disorders at Lenox Hill Hospital in New York City.
“Lumping together all Alzheimer’s patients in one group is part of the problem with inconsistent drug trial results,” says Dr. Devi, who is also the author of The Spectrum of Hope: An Optimistic and New Approach to Alzheimer’s Disease and other Dementias. “There is a lot of variability in pathology in Alzheimer’s between patients, and that’s one reason why clinical trials may vary in results. We need to better characterize which group of patients with AD respond to which drug.”
Aducanumab also has side effects, including brain swelling that, so far, seems to be temporary. (The side effect is called amyloid-related imaging abnormalities, or ARIA).
Some people experience headaches, confusion, vision changes, nausea, or dizziness.
As part of the accelerated approval, Biogen must now conduct a new randomized, controlled clinical trial to verify (or not) the benefits of the drug. That leaves open the possibility that the drug could be withdrawn from market.
Will doctors prescribe it?
Dr. Devi will prescribe the drug to patients. So will Dr. Masdeu, who described the approval as a “huge development.” But he’ll prescribe it only to patients in the early stages of the disease.
The FDA approved aducanumab for use in all stages of Alzheimer’s disease even though the drug has only been tested in patients with mild dementia and mild cognitive impairment.
Many doctors may have no choice if patients or their families request the drug, which could start shipping in two weeks.
“I probably will have to prescribe it,” says Dr. Novikova. “But I will probably offer it to a specific population of patients with Alzheimer’s disease [those still in mild stages], and I plan on cautiously waiting for the Phase 4 results.”
And, of course, there will be a discussion on the risks and benefits.
For his part, Dr. Morris says he would not recommend the drug, but he would prescribe it to patients who insist upon it, after a discussion of the pros and cons.
Dr. Salinas says his group is still discussing whether they’ll prescribe the drug and that much of the discussion revolves around who will get it and when.
“Deciding who would be a good candidate will likely depend on a lot of different factors,” he says.
A high price tag
Complicating the issue further, aducanumab is expected to cost $56,000 a year, and it’s unclear how much of the expense insurance companies will pick up.
Other tests associated with the drug, such as brain imaging, are also very expensive, Dr. Morris points out.
“There’s a strong chance the price will create even greater health disparities,” Dr. Salinas says. In other words, even if the drug worked miracles, it may only be an option for those who can afford it.
“We need to educate people who are affected by this condition so they can make decisions for themselves,” Dr. Novikova says. “It is a big deal, but it’s also a little bit worrisome on how the approval process has happened and what it means for other medications in the pipeline.”
- Alzheimer's Association: "Alzheimer's Association Welcomes FDA Approval of Aducanumab"
- John Morris, MD, director of the Knight Alzheimer Disease Center at Washington University School of Medicine in Saint Louis, Missouri
- Joseph Masdeu, MD, PhD, director of the Nantz National Alzheimer's Center at Houston Methodist
- Marina Novikova, DO, director of the Center for Cognitive Health at Henry Ford Hospital in Detroit
- Food and Drug Administration: "FDA Grants Accelerated Approval for Alzheimer's Drug"
- Joel Salinas, MD, cognitive-behavioral neurologist at NYU Langone Health in New York City
- Food and Drug Administration: "FDA's Decision to Approve New Treatment for Alzheimer's Disease"
- Gayatri Devi, MD, neurologist at Lenox Hill Hospital in New York City
- Food and Drug Administration: "Aducanumab (marketed as Aduhelm) Information"