At AAIC, We Tracked Down Answers to Readers’ Alzheimer’s Drug Questions

I’m writing from Amsterdam, where this past week, the Being Patient editorial team has been reporting on the biggest news from the Alzheimer’s Association International Conference. See some of the week’s biggest stories — from the latest on a disease-modifying pill to slow Alzheimer’s, to the soon-to-be-available at-home finger-prick Alzheimer’s blood tests — below.

Among these stories, you’ll see an recurring theme: We’re entering a new world of Alzheimer’s drug discovery with promising data out of Lilly’s donanemab study and the full, traditional level of FDA approval just granted to Eisai’s lecanemab (on the market as Leqembi). While there is a general celebratory mode in the air here at the conference, I know that the patient and caregiver population may have many questions as to what this stage of drug discovery means to them.

The week before I left for Amsterdam, Being Patient launched a survey on this new generation of Alzheimer’s drugs to gather your sentiments, specifically so that we can better understand the questions you have and what you may be considering. We’re still running the survey, so if you haven’t responded, please do.

So far, one thing is becoming clear: Our patient and caregiver community is confused about the risks versus the benefits when it comes to this new kind of Alzheimer’s treatment. I’ve spent a lot of time at this conference talking to industry experts and scientists, and here’s a cheatsheet on my biggest takeaways on these monoclonal antibody drugs for Alzheimer’s (which we like to refer to as -mab drugs, because, in reference to their drug class, so many of them end in “MAB”!).

1. These “-mab” drugs for Alzheimer’s are only for the very early stage of Alzheimer’s disease, or for mild cognitive impairment caused by the pathology that leads to Alzheimer’s.

These drugs weren’t designed to stop Alzheimer’s or reverse its symptoms — just to slow cognitive decline. And they have only been tested and approved to do that for people in the very early stages of Alzheimer’s disease.

In most patients, treatment does eliminate beta-amyloid plaque clumps in the brain — a hallmark of Alzheimer’s — within 12 to 18 months.

That feels like an important step, since these clumps of plaque in the brain are closely tied to Alzheimer’s progression, but when it comes to actually improving a person’s cognitive health to the point that activities of daily living are easy again, the difference brought about by these drugs might be hard to detect.

These drugs aren’t a magic pill. And more research is still needed to understand what clearing beta-amyloid plaque actually accomplishes when it comes to slowing or stopping Alzheimer’s disease.

2. The ‘Alzheimer’s gene,’ ApoE4, has been identified as a risk factor that could make a person more vulnerable to the side effects of -MAB drugs.

A frequent question we’re hearing from patients: Should I get a genetic test to understand whether I carry this genetic variant?

This question may be answered for you if you are considering taking the new drug Leqembi. The drugmaker has determined that there is elevated risk of side effects for people with one copy of the ApoE4 gene variant, and a more significant risk for people with two copies.

The side effect that has people concerned is ARIA, brain swelling and/or bleeding — but these can also be symptoms that come with Alzheimer’s, and while they are not a total rarity in people who’ve taken Aduhelm and Leqembi, they were often (but not always) mild cases.

(In February 2024, Biogen took Aduhelm off the market indefinitely.)

The drug maker suggests that patients taking Leqembi should get a genetic test first, but that opens a whole new can of worms for patients: Genetic tests currently aren’t covered by insurance and people’s genetic status will be in their EMRs.

Patients and families should understand the pros and cons of genetic testing — from psychological impacts to data privacy impacts — before they consider a -MAB drug.

3. Another frequently asked question: If I choose to take a MAB drug, what should my expectation be?

If you talk to a doctor, consider your options, and decide treatment with Leqembi (covered by insurance) or Aduhelm (not covered by insurance) are right for you, you are on the only disease-modifying drugs that have been approved by the FDA.

Other drugs on the market only treat symptoms. They don’t change the course of the disease. Treatment with these -MAB drugs gives patients and caregivers hope that they never had before.

4. If you are confused about the MAB drugs, your doctor may be too.

Because this class of drugs is new in the field of Alzheimer’s, not every doctor or neurologist will be able to clearly explain the nuances of treatment that comes with the complicity of administering them.

As mentioned, Leqembi’s drug label highly recommends patients do get a genetic test to understand whether they carry a gene variant known as the “Alzheimer’s gene” ApoE4. 

Regardless of whether or not a patient carries that gene variant, the label also recommends four MRI brain scans in the course of an 18-month treatment to monitor people for the signs of these ARIA brain bleeds.

You’ll undergo once-per-month infusion treatments. These infusions take around one hour, plus, in most cases, a two-hour observation period afterwards.

5. How long should patients stay on these new Alzheimer’s drugs?

Surprisingly, for now, the answer to this question depends on which doctor you talk to. Because these drugs are new, no one has a definitive answer on whether a patient will need to take infusions for the rest of their lives to ensure they keep Alzheimer’s beta-amyloid pathology at bay, or if they only need to take them until the amyloid plaque is cleared.

Read about reporter Phil Gutis’s process of deliberation. Phil lives with early-onset Alzheimer’s, and he has been taking Aduhelm since his participation in the aducanumab clinical trial. Thanks to a grant program by Biogen, he has access to Aduhelm (which is not covered by Medicare) for $250 per month out of pocket. He writes in his Being Patient column about how he sought expert advice to answer the question of whether to stay on Aduhelm, even though the amyloid plaques are now gone from his brain.

The bottom line on Aduhelm, Leqembi, and the MAB drugs soon to follow

For the first time in history, we are moving forward with drug discovery for Alzheimer’s disease.

MAB drugs are not a magic cure for Alzheimer’s dementia, but rather, a step in the right direction.

I’ve said before that I agree with the theory that treating Alzheimer’s will be similar to HIV, where a whole cocktail of drugs will be necessary to treat different aspects of neurodegeneration — but the more people who take them, the more we will understand how much value they can bring.

UPDATE: 3 March 2024, 9:03 P.M. ET. In February 2024, Biogen took Aduhelm off the market, citing financial concerns. Although the drug did receive accelerated, conditional FDA approval for the treatment of early Alzheimer’s disease in 2021, it is no longer available to new patients. The company announced it would sunset trials in May 2024 and cease supplying the drug to current patients in November 2024.