Treatment with Lecanemab (Leqembi®)?

gsergenian

I have just been diagnosed with mild Alzheimer's dementia. My neurologist has suggested treatment with Leqembi. Please share anything you know about it from personal experience or from others you know who have used it.

Iris L.

Welcome gsergenian. I believe one member is receiving infusions. Perhaps he will see your post and respond. How are you doing?

Iris

Watson1

leqembi is expensive and what may be gained only only minimal in the course of things. side affects sound alarming. i have alzheimers an am on deoplozin (aracept) which is helping. research, research!!!!!

LindaOsw

I began leqembi on Sept 5. I have APOE 4 and was clearly informed of my increased risk of serious consequences because of this pair of genes. It was not a hard decision. Unfortunately just before my third infusion I experienced serious symptoms. I am much better now, but would not consider restarting the infusions nor would my neurologist administer them. I don’t regret embarking on that path and would be pleased to share details, but don’t want to give anyone more information than they’d like. To my surprise, I could feel an improvement in that short time. Not dramatic, but noticeable

As to the expense my insurance company after I had spoken to them directly, told me I would have no copayment. About 6 weeks after the first infusion, my Dr was notified that I owed $500 for each infusion. I had a lengthy discussion with my insurance company and understood that I would get a decision in 30 days. When I called back after realizing it had been more than 30 days I learned. That there was no appeal and that while it was true I had no copay, I did owe a coinsurance of $500 for each infusion. I didn’t have to make a decision because I had already stopped my infusions.

In spite of what my Dr called a very serious reaction, 3 days in the hospital, more monitoring MRI s and lingering headaches I feel it was worth trying.

If anyone has questions about my experience I will do my best to answer

Linda

LBC83

> @gsergenian said:
> I have just been diagnosed with mild Alzheimer's dementia. My neurologist has suggested treatment with Leqembi. Please share anything you know about it from personal experience or from others you know who have used it.
I just had my 12th infusion of Leqembi. Zippo side effects so far, today I ran 3 miles a few hours after my infusion. Before starting Leqembi, I studied the Phase 3 clinical trial results. I have one copy of the APOE4 gene, the study results indicate that 14% of people with this APOE4 gene type developed ARIA-H, and 11% ARIA-E. I deemed these odds reasonable to slow down the disease progression by 27%.

gsergenian

https://alzconnected.org/discussion/comment/228747#Comment_228747

Linda, I am interested in more information. I also have APOE 4 and am therefore at higher risk. Did you have brain leaks or bleeding? Thanks for any additional information.

allit

My wife has been getting infusions. She had her fifth infusion last Friday. She had an MRI after her fourth infusion and there’s a spot that looks suspicious for a bleed. But the neurologist recommended continuing the infusion and she will have another MRI after her sixth infusion. She does not have the APOE4 gene at all.

I can’t say for certain that we notice any improvement in her Alzheimer’s symptoms but really we shouldn’t expect any. If anything, the data only shows a slowing in progression and nothing about a reversal. There’s three year data now that shows benefit. For us, it will be helpful to slow progression so that hopefully I can make it to retirement in 2026. Then I can have more time to focus on caregiving. And who knows, maybe a better option will come along that truly does stop progression. We can only hope.

https://www.neurologylive.com/view/open-label-extension-data-shows-lecanemab-continued-effect-alzheimer-disease-after-3-years

Margaret Hanley

I am awaiting infusions of Leqembi since my Neurologist was ill. I'd like to know the number of treatments and the frequency of the infusions. Also, what have been the side effects?

I figure this may be my last year for skiing and had hoped to do so after the holidays.

LBC83

Leqembi was approved by the FDA in Jan 2023 for bi-weekly infusions. Based on the original clinical trials, the standard therapeutic Leqembi treatment is for 18 months. At the July 2024 Alzheimer's Association International Conference, a representative from Eisai (manufacturer of Leqembi) was asked during a presentation about Leqembi at what point doctors should transition patients from Leqembi therapeutic dosing to maintenance dosing. The Eisai rep said their analytical modeling suggestions 18-24 months would be a good date for switching from a therapeutic dosage to a maintenance dosage. They said the company is in discussions right now on this very topic with the FDA. They were also asked when to stop treatment, and the representative said that treatment could be terminated when the patient has progressed to moderate dementia. At that point, the amyloid therapy in Leqembi does little good.

The worst side effect is ARIA, an unusual acronym as it stands for Amyloid-Related Imaging Anomaly. It is so-named due to weird things showing up on MRIs, including swelling. For us lay people, a simpler description might be bleeding in the brain. This can be a very bad thing, hence the standard protocol for anyone starting Leqembi infusions is to have an MRI prior to starting treatment, and then additional MRIs before the 5th, 7th, and 14th infusions. Other side effects include: headache, confusion, dizziness, vision changes, nausea, difficulty walking, and seizures.

There is lots of info about Leqembi on the drug maker's website at

https://www.leqembihcp.com/

Margaret Hanley

https://alzconnected.org/discussion/comment/230196#Comment_230196

MaryMN

https://alzconnected.org/discussion/71183/treatment-with-lecanemab-leqembi

My husband has been diagnosed with mild cognitive impairment due to Alzheimer's (confirmed via a PET scan). He just had his 14th infusion and has had no side effects after the first infusion - and then it was just a headache and chills. He makes sure to hydrate before infusions, which seems to help. MRI's to monitor for possible brain bleeds have all been negative.

Is he any better? No, but he's also not any worse which I think is the goal.

We actually met with his neurologist today, who said they may start recommending follow up PET scans after 12 - 18 months of treatment to measure any change in the amyloid build up. It's a work in progress.

fussbudget

My DW has been on leqembi for nine months, about halfway. She has APOE 4 homozygote meaning she has both genes, and no brain bleeding (three MRIs required). We are very hopeful that it will give her more time, the studies have shown substantial reduction even complete removal of amyloid plaques. The decision to proceed was not hard for us: the risks are not that daunting, the rewards are the only ones realistically available. The real problem was the possibility that doctors would not treat because of her genetic profile. Thank God for NYU.

LSW_Johnson

I am a social worker who works with patients who receive the Leqembi infusions and will also be the social worker for patients who will receive the Kisunla infusions when we begin administering that to patients. The Leqembi infusions are twice a month for 18 months. In between receiving infusions MRIs are done after a certain number of infusions. For my patients we do them before their 1st infusion after their 7th, 11th, and 25th infusions. The MRIs are required because there is a risk of micro brain bleeds and swelling in the brain vessels. Anyone who has an Alzheimer's diagnosis is already at risk of the bleeding and swelling without receiving any treatment. You become higher risk for the bleeding and swelling because the infusions are pulling out the proteins that cause Alzheimer's. The goal of the Leqembi and even Kisunla is to essentially freeze you at the time where you will be your most cognitive and independent hence why we only give it out to those with mild cognitive impairment or mild dementia. We want to stave off your Alzheimer's worsening for as long as possible.

David1946

Hello everyone, The VA took us Veterans to see A Christmas Carol last night it was fantastic.

LBC83

https://alzconnected.org/discussion/comment/230959#Comment_230959

I think you meant to say the Leqembi infusions are bi-weekly, not twice a week? The standard Leqembi treatment is one infusion every two weeks.

I'd also note that Leqembi does not stop the mental decline. Rather, the Phase 3 trial with Leqembi showed that it slowed the decline. Below is a plot from the Leqembi website, showing the average change in the score on the Clinical Dementia Rating - Sum of Boxes (CDR-SB) test. This is a standard test for measuring cognitive capabilities, assessing three areas of cognition (memory, time/place orientation, judgement/problem solving) and three functions (community affairs, home and hobbies, and personal care). A score of zero in a category means no impairment, a score of 3 indicates severe impairment. As an example, for homes & hobbies, a score of 0 indicates life at home and hobbies are well maintained. A score of 0.5 in this category indicates these abilities are slightly impaired, there is a mild but definite impairment for a score of 1, very restricted interests for a score of 2, and a score of 3 means no significant function in the home or in hobbies.

Everybody in the Phase 3 Leqembi trial presumably had some decline in CDR-SB score over 18 months, whether the participant was receiving placebo or Leqembi. The success of Leqembi was measured by the difference between the average degradation of those on placebo vs those on Leqembi over the 18 months.

Let us continue the example for the homes & hobbies category. Say there were two participants in the Leqembi study, both about the same gender, age, and APOE4 type. One was on placebo, the other was taking Leqembi. Assume they both scored zero in the homes & hobbies category at the start of the trial (i.e. zero degradation). Say after 18 months, the person on placebo scored a 1 in this category (mild impairment), while the person taking Leqembi scored a 0.5 (slight impairment). The difference in the sub-category score would be 0.5 -1 = -0.5. Again, there is no reporting from the Phase 3 Leqembi trial on how individuals did on the CDR-SB sub-category scores. We only know the *average* CDR-SB total score for those on Leqembi and the *average* total score for those on the placebo. The researchers then calculated the difference between these two average values.

The Figure below is showing the change in the CDR-SB scores for three groups of people. I copied this from the Leqembi website. First off, note that all of the curves start at 0 at day 0 (i.e. by definition, no change in the average degradation scores on the first day). The top line shows that for those on Leqembi, their average CDR-SB score dropped 3.16 points over 18 months.

The next line down (gray, then dashed purple) is complicated. These folks were on placebo for the first 18 months, and they declined faster than those on Leqembi over this period. The people on placebo then switched to receiving Leqembi at 18 months (the dashed purple line). The medication slowed their degradation, but note they still end up with an overall lower in CDR-SB score after 36 months of 3.46 compared to those who received Leqembi the entire time. Another way to say this, delaying taking Leqembi for 18 months for some reason means you would start the medication with a slightly declined mental capacity.

The bottom (blue) line is labeled ADNI (Alzheimer's Disease Neuroimaging Initiative). As there was nobody left on placebo after 18 months, to compare Leqembi to an "average" person with Alzheimer's, the researchers used data from the ADNI program. The ADNI study is free, anybody can sign-up on the web at adnil.org, if you are 55-90 and live near an ADNI site. They have been tracking people with Alzheimer's for a long time. Participants answer some questions online and take a memory test. Then you return every 6 months for more questionnaires and memory tests. Some participants volunteer to have blood work performed, and brain imaging, all at no cost. Back to the Figure, the ADNI line closely matches those on placebo for the first 18 months, as expected. The ADNI line continues to diverge from the two lines of those on Leqembi for months 18-36.

In summary, Leqembi does not stop degradation due to Alzheimer's. Rather, Leqembi slows the degradation. Some people draw horizontal lines on this plot from the 3.16 value for Leqembi, to see where it crosses the blue ADNI line. With this methodology, one can calculate that Leqembi buys the user about 6 months for a given capability per the CDR-SB. Others note the difference between the average scores at 36 months for those on Leqembi (3.16) vs ADNI (4.03) is 0.87. The percentage reduction in slowing is then 0.87/4.03 = 21%. This number is often quoted in news articles on Leqembi (i.e. "Studies have shown Leqembi slows the progression of Alzheimer's by 21%").

LSW_Johnson

https://alzconnected.org/discussion/comment/230967#Comment_230967

Thank you for catching my typo. You are right, the medication needs to be dosed a minimum of 14 days from each other

LBC83

For completeness, below is a plot of the change in CDR-SB score for Kisunla in the clinical trial, obtained from the lilly website. The top line is the reduction in CDR-SB score from baseline for Kisunla, the bottom line is placebo. After 76 weeks, the mean reduction in CDR-SB score is 1.72 for Kisunla, compared with a reduction of 2.42 for Placebo. This is a 29% slowing in degradation for those using Kisunla compared to those on placebo over 76 weeks.