What is the new Alzheimer's disease medication - and who should get it?

UCLA Health’s Dr. Keith Vossel explains the science behind the newly approved drug Aduhelm.

Photo: Dr. Keith Vossel, right, works in the lab. Dr. Vossel is director of the Mary S. Easton Center for Alzheimer's Disease Research at UCLA.

On Monday, June 7, the U.S. Food and Drug Administration approved Aduhelm (aducanumab), the first new drug approved for Alzheimer’s disease in almost 20 years. While the approval process has aroused some controversy, the drug could provide hope for patients facing a terminal diagnosis.

“If one is falling from an airplane, and they have a parachute, and the cord may or may not work, most people would want to pull that cord,” says Keith Vossel, MD, director of the Mary S. Easton Center for Alzheimer's Disease Research at UCLA. “It is possible that this drug will help some individuals and not others, and there are significant side effects to be aware of.”

Here, Dr. Vossel explains how the new drug works, who might benefit from it, and what this means for the future of Alzheimer’s treatment.

Q: What is Aduhelm?

A: The drug is a monoclonal antibody. It’s similar to a vaccination, but rather than injecting a foreign substance that causes our body to create antibodies, the drug is a form of antibody that is infused into our system, and it binds to these sticky fragments in the brain called amyloid beta peptides. They are the components of amyloid plaques, which are the hallmark features of Alzheimer's disease, along with tau tangles. (In healthy brains, tau protein helps build the structures that transport nutrients within nerve cells. In Alzheimer’s, these structures collapse and tau forms tangled clumps.) The infusion of these antibodies over time helps the brain to clear these plaques effectively.

Q: Do amyloid plaques cause Alzheimer’s disease?

A: The amyloid hypothesis posits that amyloid beta is the primary driver of cognitive decline. There are many steps that probably occur after amyloid plaques form, and the field as a whole was hopeful that this type of treatment would have significant effects to slow decline or even halt decline. What we're seeing is that the effects of the treatment, if they do exist, are fairly small.

Note: Amyloid beta is a protein in the brain whose normal function is not well understood. In Alzheimer’s, amyloid beta forms plaques that interfere with the healthy functioning of brain cells.

Q: Did Aduhelm slow the decline of patients in the trial?

A: The potential benefit was small. One of two phase 3 studies indicated that the drug could slow disease progression by about four months, when given over a year and a half.

Q: Why was the FDA decision controversial?

A: Well, normally, for the FDA to approve a new medication, there need to be two phase 3 studies that prove that the medication is helping with the intended symptom. For Alzheimer's disease, we would like to find a therapy that slows the disease course, because we already have treatments that improve symptoms. There were two phase 3 studies done with this drug, and both studies showed that the drug removed amyloid plaques. However, only one of the two studies showed a slowing of cognitive decline over 78 weeks.

There are many potential reasons for this, so the FDA took a different and controversial approach. They approved this drug under the Accelerated Approval Program, which allows approval for a drug that could help a disease that is terminal. This pathway is usually used for rare diseases. The drug is not approved as a demonstrated treatment to slow cognitive decline. It is approved based on its ability to remove amyloid plaques, which the FDA states “is reasonably likely to predict important benefits to patients.” Doctors will have to have lengthy discussions with patients on risks and potential benefits of this drug.

Q: Let’s start with the benefits. What kind of patient would qualify for this medication?

A: Well, the clinical trials were restricted to people in the mildest stages of Alzheimer's disease. These are people who still have nearly full independence and are just beginning to show some cognitive symptoms.

It takes an astute clinician who is knowledgeable about dementias, and this could be a neurologist, a geriatrician or a geriatric psychiatrist who is familiar with Alzheimer's disease and can rule out other conditions that can mimic Alzheimer's disease. To confirm the diagnosis, we would need either PET scan images of the brain, where we can see the amyloid deposits, or a spinal fluid exam, which is just as accurate at determining whether amyloid is elevated in the brain.

The scientific evidence suggests that we should restrict the drug to the people with mild disease, because we have no idea if it's going to improve symptoms, or even make things worse, in patients who are more advanced in the disease, or who have not developed the disease yet. Some patients with amyloid positive scans never develop Alzheimer's disease.

Q: What are the risks?

A: There are many side effects that can occur, including brain swelling and small areas of hemorrhage or bleeding. It can cause headache, dizziness, confusion and falls. And all of those are things that we need to be vigilant about, if we are to give the medication.

To monitor for side effects, we first need to test for the gene APOE. One version of the gene, called APOE4, confers higher risk for Alzheimer's disease. Patients with APOE4 also have higher risk of brain swelling with the drug. It occurred in 40% of the patients on the highest dosage, and it's even more common in those with APOE4. Therefore, at UCLA we’re planning to get APOE4 testing before we administer the drug.

Even though there are side effects, the trial proved that patients can continue the medication through adjustments in their treatment, even if they do develop side effects.

Q: How much will it cost?

A: The estimated cost by Biogen is $56,000 per year per person. This does not include the costs of numerous brain scans and blood tests required to give the drug. It’s unclear yet what insurance companies and Medicare Plan B will cover.

Q: How would you advise someone who has not yet been diagnosed with Alzheimer’s disease, but is having memory problems and wonders whether it’s time to try this treatment?

A: The memory concern comes up a lot. And many people wonder, “Is this a senior moment or is this a real concern?” So the first step is to talk with their primary care doctor about it. If there's a family history or another reason to be concerned based on the symptoms, typically there will be a referral to a specialist and potentially neuropsychological testing, which is like a test drive for the brain. It gives us a sense of how our brains are working in relation to age- and demographic-matched controls.

Q: Do you think this is going to lead to more drugs being approved in the near future?

A: This drug’s approval could hamper other clinical studies in the short run because patients may prefer to be on an approved drug rather than entering a trial. Also, with this precedent, other amyloid-lowering drugs may gain FDA approval without showing clinical benefit. We need to design clinical trials that account for patients being on aducanumab, or related drugs, and then see what additional treatments could help in preventing, slowing or halting Alzheimer’s disease.

Caroline Seydel is the author of this article.