MCI-- treatment with Lecanemab or Donanemab

grabotex

This is my first post. I am a caregiver for my DW who was recently diagnosed with MCI with an APOE 3/4. We will be having an important discussion soon with a neurologist who is going to present us with the two possible treatment options of either Lecanamab or Donanemab; but we are quite fearful of the possible negative consequences with adverse side effects and are seriously wondering whether or not we all as a family want to start down this road. Currently my DW has little short term memory with some agitation and takes Donepezil and Sertraline to help with agitation. Are there any suggestions from the community from similarly situated dementia family who might be able to share some reflections for us to consider prior to our meeting with the neurologist. We appreciate any stories you can share and thank you so much.

LBC83

I was diagnosed with MCI in April 2024. I am also APOE 3/4. After much research, I elected to start on Leqembi. I just had my 15th infusion, with zippo reactions. I am aware of the concerns with ARIA (Amyloid Related Imaging Anomaly), which include swelling and bleeding in the brain. In the clinical trials, most occurrences of ARIA had no side effects (they were only noticed in the early mandatory MRIs whare are taken after the 4th, 6th, and 13th infusion). The few with severe ARIA had some nasty outcomes. However, for many of them, the issues went away after stopping treatment. Seems like life in general - there is always some risk, such as driving on a highway to visit relatives. There are lots of car accidents in the U.S. and tens of thousands of people die each year, but most of us don't worry about such things when we set off on a trip. I found the risk vs reward decision pretty easy.

Today there are the two products you mentioned. I happen to like to use the common names of Leqembi and Kisunla. The both had similar results in their Phase 3 trials in terms of percentage reduction in the Clinical Dementia Rating - Sum of Boxes score after 18 months of treatment (29% reduction with Kisunla, 27% reduction for Leqembi). If you are unfamiliar with the CDR-SB methodology, it is apparently standard in the AD world, determining how well people perform on a test involving memory, orientation, judgment, community affairs, home 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 home & 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. In other words, this seems to be a very practical test to see how well a person can operate in the world.

Keep in mind the above numbers are averages over the entire population of those participating in the trials. The detailed numbers are available split by age (older folks had larger reductions than younger folks), gender (males had larger reductions than females), and APOE4 status (noncarriers had largest reduction, followed by heterozygotes, and then homozygotes). However, I think all of these are not so useful, as they include people with varying degrees of cognitive decline at the start of the trial. People in your shoes would really want to know how people of your gender/age/APOE4 status AND a specific starting cognition might perform with the drug. Alas, that sort of information isn't available.

Kisunla is dosed via a monthly IV, Leqembi is currently a bi-weekly infusion. Leqembi has been around longer (approved by the FDA in Jan 2023) versus a July 2024 approval for Kisunla. Eisai (Japanese company that manufactures Leqembi) likes to advertise that Leqembi works by "by continuously clearing protofibrils and rapidly clearing plaque" (quoting from a recent Eisai press release). Thus, people on Leqembi stay on Leqembi until their cognitive decline gets to a point where folks decide treatment should end. With Kisunla, treatment stops after amyloid is cleared from the brain.

Yesterday, Eisai issued a press release stating that the FDA accepted their application for a subcutaneous version of Leqembi for maintenance dosing (i.e. people could use this after 18 months or so of initial treatment). The idea is this shot could be performed at home, avoiding IVs. Again, this is for maintenance dosing only, folks still have to have about 18 months of initial IV treatment. The press release indicates the FDA set an action date for the Eisai application on Aug 31, 2025 (i.e. the date when the FDA might approve the Eisai application).

I am not sure how the end user costs compare for the two drugs. My co-pay for my bi-weekly infusions of Leqembi is around on $400. I'm on a private medical plan (not old enough for Medicare).

In other comparisons I've seen between the two drugs, nobody mentions the dosage. For Leqembi, the dosage is dependent on your body weight: 10 mg of Leqembi per kg of body weight. For example, my dosage is 600 mg of Leqembi (I weight over 60 kg which is 132 pounds, but they apparently round down to the nearest 100 kg). Kisunla is a fixed dosage of 700mg for the first 3 and later doses are 1400 mg. So if you are heaver or lighter than average weight, you might be getting less than average or more than average dosage of Kisunla, respectively.

I think the following website has a good comparison of Leqembi & Kisunla.

https://www.beingpatient.com/leqembi-vs-kisunla-for-alzheimers/

LBC83

One other thing. If you use Facebook, you could consider joining the "Leqembi Support Group" (it is a restricted group so you have to request membership). There, you will find oodles of posts by people on Leqembi (very sparse posts by people on Kisunla). Many people have recently posted in their early infusions. Some had infusion-related reactions, such as nausea, which were also noted in the clinical trials.

While I'm posting again, below is a Table extracted from the paper explaining all of the adverse events in the Phase 3 clinical trial for Leqembi. It is a long list. From one perspective, the important thing is to compare the two columns (Leqembi vs Placebo), as you presumably are most interested in the impact of receiving Leqembi. But it also can be useful to compare the numbers between the two columns (such as a higher number of people who were on placebo had diarrhea compared to those on Leqembi).

Finally, the Leqembi website has lots of good information:

https://www.leqembihcp.com/

grabotex

OMG thank you so much for this valuable and detailed aspects of this complicated decision. I assure you it will be very helpful to us. God Bless and best of luck with your own challenges.

South Dakota Dave

I was diagnosed with Alzheimer’s; in April 2024. After dealing with local Dr.’s which failed us too often we decided to drive 635 miles to the Mayo Clinic in Rochester MN to confirm my diagnosis and see if I was a candidate for Leqembi. We found it the best thing we ever did. We feel it important that your neurologist is experienced with Alzheimer’s and a good match for you as well. Our neurologist is the only one could find in our community, barely versed on Alzheimer’s, but our Mayo Dr’s will react quickly when needed.

I was one of about 14 Alzheimer’s patients. The required infusions started on January 2024; to date (1/14/2025 now) I now have had 27 infusions each two weeks apart, each in a hospital completed within about 2 ½ hours. We plan to continue this until August 2025 when we return to Mayo. I will have a PET scan to hopefully continue on with Leqembi and soon enter in the new at-home program.

A few days ago, we heard of a new FDA approval scheduled for Leqembi that will arrive sometime about August 2025. I am much more hopeful now because we find Eisai (the owner) Leqembi has already been using their subcutaneous (SC) injector with Leqembi which gets us out of the infusion center into a new at-home procedure to administer Leqembi much faster and less costly and importantly showing the SC formulations resulted in 14% greater amyloid removal!

It may be helpful to know that anyone that has Medicare, I’d suggest getting a good health supplement also. Reason: Medicare currently pays for Leqembi (great!) but the required infusions are not covered. In my state (South Dakota USA), the cost for that is $1600 each month. BUT our supplement insurance covers it 100% with only a $190 cost each month.

We’ve learned a lot from the 27 infusions I've had and would be glad to help with any questions or concerns about Leqembi.