A Former AD Care Partner’s Perspective on Leqembi

Social workers facilitating support groups for Alzheimer’s disease (AD) care partners or for people in early stages of AD should expect many questions in the coming months and years about some of the newer AD medications that are receiving, or about to receive, FDA approval. How should social workers respond to these questions that may be asked by AD patients and care partners? Aside from the obvious response that such questions should be directed to the patients’ doctors, here’s the view of one former AD care partner.

On July 6, 2023, the FDA gave full approval for Japanese drugmaker Eisai and its American partner Biogen to market its latest medication, lecanemab (to be known as Leqembi) for those with mild AD. Announcing the approval, Teresa Buracchio, acting director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research, says, “Today’s action is the first verification that a drug targeting the underlying disease process of Alzheimer’s disease has shown clinical benefit in this devastating disease. This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer’s disease.”1

That same day, The New York Times noted thatthe FDA acknowledged that Leqembi clinical trial results indicated that those taking the new medication showed a significant difference on an 18-point scale measuring cognitive functioning and memory, and that Leqembi “slowed memory and cognitive decline by about five months for those receiving the medication as opposed to those receiving the placebo.”2

However, as a doctor noted in that same article, “The benefits of slowing are subtle. You’re not going to experience the perception of changes in your cognition or function in the same amount of time.”2

In that same New York Times article, the author noted that Leqembi will carry a” black-box warning” about possible side effects such as brain swelling and bleeding, with a notation that “additional caution should be exercised” when considering whether to give blood thinners to Leqembi patients.

Elsewhere in that same article it’s noted that “Concerns about safety have been stoked by reports of deaths of three clinical trial participants who experienced brain swelling and brain bleeding, two of whom were being treated with blood thinners. Eisai has said it’s unclear if Leqembi contributed to their deaths because the patients had complex medical issues.”

According to an NBC news release online on Leqembi that same day, “About 12.6 % of patients who got Leqembi in the trial developed brain swelling, compared with 1.7% of those in the placebo group. About 17% of the Leqembi group experienced brain bleeds, compared with 9% in the placebo group.”3

I don’t think my late wife would have considered taking such a medication. Why?

Three reasons:

First, just the procedure for having to get dressed and get into the car to go to and from a doctor’s office for IV injections every two weeks for a year would have been a very stressful experience. And there would be additional doctor visits for various brain and blood scans while receiving the medication. In addition, my wife always felt pain with injections and bled readily, with her skin turning all pretty colors whenever receiving a needle for any reason, possibly due to all the heavy-duty heart medications she was taking each day as well as 325 mg of daily aspirin.

A second reason would be the side effects. AD is serious enough as it is—a death sentence with no cure and the 100% certitude of worsening conditions. Gaining a few additional months of time to continue leading a more “normal” life before cognitive and memory issues worsen even more would be wonderful, but much too heavy a price if those side effects occurred. Dealing with AD and heart disease was enough of a double whammy for my wife. Possibly compounding that with brain swelling, bleeding, headaches, and other effects of this medication would have made her situation even worse.

The final reason is the “real world effectiveness” of this new medication. Study participants taking the medication showed a gain of less than one half of one point on testing—a statistically significant outcome, perhaps, but I question how much of a clinical difference that really would have made in my wife’s life or in mine. By the time my wife was in early stages of AD, our lives had already changed dramatically. A few more months of slower decline would have been welcome but would probably not have changed much about our daily lives. Especially when one considers that the trade-off to perhaps gaining a few months of slower decline might have led to losing the quality of life we still had. Slowing decline doesn’t mean ending it, and we may not have even noticed that slowing. The added stress of two more doctor visits each month, the pain and after-effects of IV needles, and possible additional pain or hospitalization due to severe side effects of this new medication would have easily lessened whatever quality of life we still had.

Would I have loved my wife to have declined at a slower rate for a few more months in those early stages? Of course. Would I have loved to have taken more trips with her? Absolutely. But worrying about the possibility of her having a serious brain hemorrhage or other serious side effect while traveling away from home would have worried me too much to have taken that chance. In fact, I would have been worried every single day, whether at home or not, had she been taking this new medication.

I haven’t even mentioned another real-world effect of this new medication—the demands placed upon the AD patient’s care partner. Even in early stages, some AD patients may need assistance in dressing and with mobility and may angrily object to going out in bad weather or going out at a certain time of day. Helping people with AD can strain even the best of relationships. In addition, many care partners are still working when their loved ones are in early stages, and time demands of taking loved ones to two office visits each month for IV injections, along with additional visits for brain scans and other required testing to remain in this program, could be an additional burden.

And, of course, there’s the financial burden this would be for many people with AD and their care partners. Even with expected 80% reimbursement by Medicare, out-of-pocket costs would still be high for both the medication and the additional office visits and scans. “Patients with traditional Medicare will pay 20% of the bill for Leqembi, according to the federal Centers for Medicare and Medicaid Services. That means these patients could see an annual bill of more than $5,000.”4

As a former 24/7 AD spouse caregiver, I am often skeptical of reports of “statistically significant” test results because I find that, too often, such results do not translate into meaningful observable differences in the real world. There is a big difference between “statistically significant” and “clinically different.” I often think of “statistically significant” AD test results in this way. Suppose one has 2,000 equally healthy and robust house plants, each producing 100 healthy leaves, with each plant expected to live for one full year before losing all of its healthy leaves. Then, suppose a clinical trial is conducted to determine if something added to the water might produce healthier plants. During the clinical trial to test whether or not a chemical added to “enrich” the water is better than just plain water for these plants, 1,000 plants receive only regular water and 1,000 plants receive only “enriched” water for an entire year.

Then suppose that after one year, the plants receiving regular water have 99 dead leaves, while the plants receiving enriched water “only” have 98 dead leaves. If the authors of that hypothetical study then concluded that the difference in dead leaves is statistically significant by some sort of testing metric, results would still be totally meaningless to me. The plant with “only” 98 dead leaves would not look appreciably healthier to me than the plant with 99 dead leaves. Statistically significant differences? Maybe. Clinically significant differences? Not to me. The bottom line, to me, is one would have two dead plants.

I am hoping for the day when a new AD medication will prove clinically effective in the real world, which to me would lead to many, many months or years before symptoms develop, worsen, or disappear with no serious potential side effects. I don’t see that happening with Leqembi.

I won’t get too excited about Leqembi or other new medications with similar “statistically significant” results that also carry great risks of dangerous side effects. Not just yet. I have been disappointed too many times. I have seen too many dead plants.

Social workers must always be careful not to involve themselves in discussions about advantages and/or disadvantages of any medications, referring all such questions to medical personnel. As someone who has facilitated support groups for AD care partners in the past, I was often asked medical questions by participants in my group. So social workers must accept that they may be asked by some care partners, if not by people with AD, questions such as “I know you cannot give me medical advice, but as someone I trust, what would you do if it were your mother/father/sister/brother/spouse?

At least you will now have this former AD care partner’s perspective!

— Allan S. Vann is a retired public school principal and former Alzheimer’s disease (AD) spouse care partner. To date he’s had more than 100 articles about AD published in peer reviewed medical journals, caregiver magazines, on AD organizational websites, and in major newspapers. Although his wife died of AD in 2016, he remains an active AD advocate for change, continues writing for publication, and continues to serve on advisory panels to help educate professionals working with AD patients and their care partners.

References
1. FDA converts novel Alzheimer’s disease treatment to traditional approval. U.S. Food & Drug Administration website. https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval. Published July 6, 2023.

2. Belluck P. New federal decisions make Alzheimer’s drug Leqembi widely accessible. The New York Times. July 6, 2023. https://www.nytimes.com/2023/07/06/health/alzheimers-leqembi-medicare.html

3. Lovelace B Jr. FDA grants full approval to new Alzheimer's drug meant to slow disease. NBC News website. https://www.nbcnews.com/health/health-news/leqembi-alzheimers-drug-fda-approval-eisai-biogen-rcna92377. Updated July 6, 2023

4. Kimball S. Medicare will pay for Alzheimer’s drug Leqembi. What patients and doctors should know. CNBC website. https://www.cnbc.com/2023/07/08/leqembi-and-medicare-what-patients-and-doctors-should-know.html. Published July 8, 2023.