Leqembi infusions

I just had my 15th infusion of Leqembi. The phase 3 trial for Leqembi showed an average slowing in cognitive decline of 27% over 18 months. This was measured using the Clinical Dementia Rating Sum of Boxes (CDR-SB) test for measuring cognitive capability, 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 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.

The 27% value was calculated by comparing the average cognitive decrease for those on placebo over 18 months (1.66) versus the average decrease for those on Leqembi (1.21). Again, this was over 18 months. In reviewing the data, some have noted that to state this another way, Leqembi basically buys the person 6 more months at the same cognitive capability compared to someone not taking Leqembi. For example, this might mean somebody taking Leqembi might be able to spend 6 more months at home before being placed in a memory care facility. After the 18 month trial, those who had been receiving the placebo were allowed to switch to Leqembi.

Eisai (developer of Leqembi) has also published data for Leqembi after 36 months of treatment. For this case, the percentage difference in CDR-SB score is calculated using an estimate of how people might have performed if they weren't on Leqembi (because there wasn't anybody left in the study who wasn't taking Leqembi). The estimated change in CDR-SB was 22%, but the time gained by taking Leqembi is increased to around 9 months. Again, there is a caveat with these 36 month results, as they are comparing those on Leqembi with estimates of how people might have performed if they weren't on Leqembi from 18-36 months.

There are generally two concerns about Leqembi. First, some folks have reactions to infusions, regardless of the drugs being infused. Common infusion reactions include fever, chills, nausea, vomiting.

Before getting into the second concern, we must first cover a little biology. Leqembi is in a class of drugs referred to as monoclonal antibodies. This is a fancy term to describe a protein made in a lab that acts like a human antibody and binds to specific targets in the body. In this case, Leqembi binds with amyloid in your brain, serving as a warning beacon to your bodies immune system to latch onto the Leqembi (and the amyloid) and drag it out of your system. Leqembi (as well as Kisunla, a competing monoclonal antibody made by Eli Lily which also removes amyloid) can cause issues in the brain. This problem was noticed early in the development of the monoclonal antibodies, and became known as Amyloid Related Imaging Abnormalities (ARIA) as they were first noticed in MRI images taken of those receiving these drugs.

There are two types of ARIA: ARIA-E and ARIA-H.
ARIA-E: The "E" stands for edema (i.e. swelling in your brain)
ARIA-H: The "H" is for hemosiderin, or hemorrhage. If blood is leaking out of the blood vessels in your brain, then you have ARIA-H

Most cases of ARIA-E and ARIA-H are asymptomatic and are usually recognized as incidental ARIA during a follow-up evaluation on MRI.
Most cases of ARIA-E occur early in treatment and decrease with increased duration of exposure to the medicine.
Most cases of ARIA-E resolve completely. Depending on the severity, treatment may continue, be interrupted or discontinued until resolution. Some cases may require specific treatments and even hospitalization.
ARIA-E and ARIA-H may occur concurrently.
In past clinical trials with Leqembi, ARIA-E resolved radiographically over time, whereas ARIA-H can remain visible on subsequent imaging.

In the Phase 3 clinical trial for Leqembi, there is information about the frequency of ARIA-E/-H versus APOE4 gene status. 2.8% of the people on Leqembi had symptomatic ARIA-E (i.e. not very many). By APOE4 status: 1.4% of APOE4 non-carries had symptomatic ARIA-E, 1.7% of APOE4 heterozygotes, and 9.2% of APOE4 homozygotes. For ARIA-H, 11.9% of APOE4 noncarriers experienced ARIA-H, 14% of APOE4 heterozygotes, and 39% of APOE4 homozygotes. But only 0.7% of the people experienced symptomatic ARIA-H (i.e. most of those with ARIA-H didn't know they had ARIA-H until they received the MRI). Due to these numbers, I've read that some locations exclude APOE4 homozygotes from receiving Leqembi. Other organizations permit APOE4 homozygotes to receive Leqembi, but they watch these people extra carefully.

Some might ask, "What is the point of just slowing the disease?" One answer might be that there are also drugs undergoing trials right now to reduce Tau. These drugs are being tested in combination with Leqembi (which again is reducing amyloid). The idea is that the combination of these two drugs might be able to greatly reduce (or maybe even stop) the cognitive decline. Thus, buying more "quality time" may be important, such that if these anti-tau drugs pass the clinical trials and are available at a later date, they would help those who had slowed their cognitive decline by taking Leqembi.