Nearly two months after the Alzheimer's drug Aduhelm received conditional approval from the Food and Drug Administration, experts are still debating how, and whether, it should be used.
A few doctors and medical institutions say they have no plans to administer Aduhelm. Many more are trying to decide which patients should have access to the drug and how to protect them from its potentially dangerous side effects.
Alzheimer's is "an incurable condition and it's progressive," says Dr. Alireza Atri, who directs the Banner Sun Health Research Institute in Sun City, Ariz. "I think we need to figure out a way to present that option to [patients] in a way that's safe."
The latest attempt at clarity came this week at the Alzheimer's Association International Conference in Denver, where Atri and a panel of five other prominent doctors – all of whom supported Aduhelm's approval — unveiled recommendations on the use of the drug.
Controversial approval went against experts' advice
The recommendations call for limiting Aduhelm to patients in the earliest stages of Alzheimer's whose brains have the sticky amyloid plaques that are a hallmark of the disease. They also call for brain scans and other measures to detect bleeding and swelling in the brain, which can be a side effect of the drug.
"We need to be cautious and very thoughtful about how we proceed," says Atri, who has been a consultant to Biogen, the maker of the drug.
Aduhelm received what's known as accelerated approval from the FDA on June 7 despite an advisory panel's recommendation that the agency not approve the drug.
The FDA's decision was based on the drug's ability to remove amyloid plaques, rather than any proven ability to slow the symptoms of Alzheimer's.
Accelerated approval means that Biogen must conduct "confirmatory trials" of the drug's safety and effectiveness after it is on the market.
Even though Aduhelm has made it through the FDA, it is still not widely available. And it remains unclear how many payers, including Medicare, will cover the drug, which currently has a price tag of $56,000 a year.
Instructions for drug confuse doctors
Meanwhile, doctors who treat Alzheimer's patients are preparing to prescribe the drug.
Usually, doctors look to a drug's label and instructions for guidance on appropriate use and safety. But experts say that's not enough when it comes to Aduhelm.
"The label left a lot of gaps," Atri says. "So it is important to have very quickly some preliminary recommendations regarding how to use this because people are using it already."
Aduhelm presents a special challenge because it must be infused directly into the bloodstream and can cause potentially dangerous swelling and bleeding in the brain.
The recommendations presented at the Alzheimer's conference say doctors should not treat patients who already have significant problems with memory and thinking.
In these patients, Alzheimer's has progressed to the point where "they're probably not safe to be driving, they've given up most of their complex hobbies and social activities outside of the home," says Dr. Eric McDade, an associate professor of neurology at Washington University in St. Louis, who was not involved in the recommendations.
If faced with such a patient and their family, "I would say, really there is no evidence whatsoever this is going to benefit you," McDade says.
Brain scans needed to check for side effects
McDade also supports a recommendation that doctors obtain a brain scan or a test of spinal fluid before giving the drug to confirm the presence of amyloid plaques. These plaques are absent in more than a third of people with symptoms of dementia.
"Listen, if you are considering using this drug for a patient, it's incumbent on you to ensure that [they] have amyloid plaques in their brain," McDade says.
Other recommendations include ordering brain scans if patients experience headaches, dizziness and other potential symptoms of swelling or bleeding in the brain.
The recommendations are intended for specialists, primarily neurologists, says Maria Carrillo, chief science officer of the Alzheimer's Association, which supported approval of Aduhelm.
Most primary care doctors, she says, lack the training or facilities to offer Aduhelm.
"We're hopeful that these recommendations can be used by those neurology clinics around the country that do not traditionally participate in clinical trials, so they do not have the experience for setting up this type of clinic," Carrillo says.
But during a session at the Alzheimer's conference, even senior research scientists had questions about using Aduhelm.
Several discussed the difficulty in planning treatment for Black and nonwhite Hispanic patients, who were largely left out of research studies on the drug.
They noted that those studies found that people with a genetic variant called APOE4 are twice as likely to experience side effects from Aduhelm.
"Unfortunately, we don't enough about the impact of APOE4 on underrepresented populations, in particular on African American or Latinx backgrounds," Carrillo says.