Leqembi

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Hi, this is Teri.  I am a 3rd generation Alzheimer’s Survivor and a co-caregiver of a parent who is surviving and thriving despite having Alzheimer’s Disease.

Recently, we have talked about what Alzheimer’s is, different types of Alzheimer’s Disease & what causes Alzheimer’s Disease. After laying that groundwork we can finally discuss and review new medications and treatment solutions for Alzheimer’s.

We will start this series of blogs reviewing Leqembi (lecanemab). 

As in the last blog, I will remind you, I am not a doctor.  I am not a medical professional.  I am a person who can take detailed medical information, research it, and create content & imagery that will make it easier for you to understand a specific concept.  You should NEVER use my content to make medical decisions for yourself or your loved one. However, you can take the content I provide to begin conversations with your doctor.  

What is Leqembi? 

Leqembi is a medication that is used to treat early-stage Alzheimer's Disease. It is an FDA-approved treatment that targets one aspect of the underlying biology of the disease. Leqembi works by reducing the amount of amyloid-beta proteins in the brain, which are a key factor in Alzheimer's Disease

Leqembi is administered as an intravenous (IV) infusion every two weeks at an infusion center. Each infusion usually lasts about an hour. Leqembi is approved for people with mild Alzheimer's disease, which means they have some memory and thinking problems, but their symptoms are not severe. It can also be used to treat mild cognitive impairment (MCI) and mild dementia due to Alzheimer's disease. 

It is important to note that Leqembi is not a cure. I will repeat it to be clear.  Leqembi is NOT a cure for Alzheimer’s Disease. Alzheimer’s Disease is triggered by multiple conditions such as diabetes, genetics, toxic environmental exposure, and inflammation. Leqembi was designed to slow Alzheimer's progression by identifying and attacking beta-amyloid proteins in the brain. 

This is significant because beta amyloids are one of the hallmarks of Alzheimer’s. These proteins clump together to form plaques that destroy neurons. Neurons are the cells that form the brain’s communication system. Leqembi is a monoclonal antibody that binds to these plaques and breaks them apart.

What is a monoclonal antibody?

Monoclonal antibodies (mAbs) are laboratory-made proteins that are a type of targeted therapy used to treat a variety of diseases, including some types of cancer and COVID-19. Monoclonal antibodies are highly specific because they are derived from a single clone of cells and are engineered to closely reflect the structure of naturally produced human proteins. This means that the body handles them similarly. The body does not metabolize monoclonal antibodies like it would a synthetic medication. 

 mAbs are created in a lab from living sources that produce antibodies, such as human B cells.  Or immunized animals. The first step in the process is to express a purified antigen, which is often a critical step. The mAbs are then produced by identical clones of B lymphocytes against a specific antigen.

How are monoclonal antibodies produced?

The traditional monoclonal antibody production process usually starts with a generation of mAb-producing cells (i.e. hybridomas) by fusing myeloma cells with desired antibody-producing splenocytes (e.g. B cells). These B cells are typically sourced from humans or animals, usually rodents.

Human mAbs can be used to target and neutralize specific proteins that induce an immune response, such as those associated with inflammation in psoriasis and other autoimmune disorders. Leqembi is an example of a human mAb used to treat Alzheimer's disease.

Advantages of using mAbs:

• Precision - mAbs are more precise than other treatments, which can improve effectiveness and reduce side effects. For example, monoclonal antibody therapy can target cancer without damaging healthy cells.
• Safety - mAbs are safer and less toxic than chemotherapy drugs, which can improve patient survival and well-being.
• Quality - mAbs quality is consistent across production batches, which is important for both therapy and diagnostics.
• Quantity - mAbs can be produced in large quantities.
• Other advantages - mAbs also have fewer off-target adverse effects, fewer drug-drug interactions, and higher specificity.

Disadvantages of mAbs in an overview

• long lead times for traditional mAbs manufacture methods (hybridoma)
• relatively high cost of goods
• laborious process, hybridoma cell generation has low yields
• selectivity is hard to achieve for peptide targets with few amino acid residues
• contamination and risk of loss for hybridoma cultures
• limited uses due to the mode of action

It is not uncommon to have an infusion reaction when taking mAbs.  It is like an allergic reaction. Symptoms can include fever, chills, weakness, headache, nausea, vomiting, diarrhea, low blood pressure, and rashes, and are more common when the drug is first given. This is your body’s response to taking a biological medication and will usually subside as you get used to it.

Who can take Leqembi?

Now that we understand what Leqembi is and how it works.  Who can take Leqembi?

In theory, anyone experiencing mild cognitive impairment or the early stages of Alzheimer’s Disease.  However, to qualify for treatment with Leqembi, patients must meet the same criteria used in the clinical trials that led to its approval:

• Be between the ages of 50 and 90
• Have a confirmed presence of beta-amyloid plaques in the brain
• Have mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease
• Have a body mass index (BMI) between 17 and 35

Potential patients must undergo diagnostic testing to confirm the presence of beta-amyloids before starting treatment, which is usually done with a PET scan and/or a spinal tap. Leqembi has not been tested on people with more advanced Alzheimer's or those without symptoms, so they do not qualify for treatment. 

Side Effects of Leqembi

There are potential side effects with every medication.  No one should be surprised that there are side effects with Leqembi.  The following information was taken word for word from Eisai and Biogen, the manufacturers and distributors of Leqembi:

LEQEMBI can cause serious side effects, including:

• ARIA (amyloid-related imaging abnormalities). There are usually no signs of ARIA. In rare cases, it can lead to serious complications
• ARIA can show up as swelling in parts of the brain or small spots of bleeding
• Larger areas of bleeding in the brain may occur, but this is uncommon
• ARIA usually goes away over time
• Most people with ARIA don’t have any symptoms. However, some people may notice:

–headache
–confusion that gets worse
–dizziness
–vision problems
–nausea
–problems walking
–seizures

• Some people have a gene called ApoE4 that may increase the risk of ARIA. Talk to your healthcare provider about testing to see if you have this gene
• Some medicines can increase the risk of larger areas of bleeding in the brain for people taking LEQEMBI. Talk to your healthcare provider to see if any of the medicines you’re taking increase this risk
• Your healthcare provider will check for ARIA with MRI (magnetic resonance imaging) scans before you start LEQEMBI and during treatment

I want to be careful to not over-dramatize these side effects.  As I have said in previous Blogs, I am a study buddy for a loved one participating in a research program with (BAN2401) Leqembi.  My loved one has experienced Aria-E and Aria-H. 

The Aria-H experience was by far the most dramatic of the two.  It started when my loved one woke up from a deep sleep after feeling and hearing what she described as an explosion in her brain.  She said it felt like she had been hit by a brick.  She sat up and placed her hand on top of her head as you would when something just hit you.  When she removed her hand to look at it, she fully expected to see blood on her hand.  But there was no blood. She got up out of bed, went to the bathroom, made a note in her journal, laid back down, and went back to sleep. 

There are some important things to point out here:

She said she felt like she was hit with a brick.  However, there are no pain receptors in the brain. And later she would say that it felt like being hit by a brick but without pain.  I say this to be clear that as traumatizing as it was, there was no pain.

She calls it an explosion in her head.  She is confident that she heard the sudden micro hemorrhage take place.  And that she heard the blood flow.  I am 100% confident that she did.  My loved one is not one to over-dramatize facts.

But how big was this hemorrhage?  To be classified as a micro hemorrhage it must be smaller than 5 millimeters in diameter.  How big is that?  The size of her micro hemorrhage was between the size of the tip of a pencil lead and half the diameter of the eraser tip.  VERY small. 

Despite the potential of brain swelling and another brain bleed, I stand behind her choice to continue to take Leqembi.  Knowing that any day, I might get a phone call with her telling me it happened again.  Because without this medication, I believe her cognitive decline will become significant.  We are not giving up on her and her desire to be a volunteer for Alzheimer’s research.

How do I get started?

OK, so you heard all about the scary potential of experiencing a brain bleed and potential brain swelling.  You understand that by taking no action, you are guaranteeing continued cognitive decline.  And you want to start the evaluation process to see if you are a good candidate for Leqembi treatment.  How do you get started?  There are 2 options:

Schedule an appointment with your neurologist to learn more.

• If you do not have a neurologist or if you want to be sure you are working with a Leqembi-friendly neurologist, send me an email (teri@protonmail.com).  I will need to know where you are located.  With that information, I will get back to you with a couple of options.
• This is a great option if you have insurance that will pay for all or part of the testing and medication.

Schedule an appointment with an Alzheimer’s Research facility. 

• Research doctors have the same qualifications as neurologists in private practice.   However, most research studies do not guarantee that you will receive the medication in the first round.  You may receive a placebo first and the study medication later.
• Research studies often offer protocols that are not available to the public yet.
• If you do not have insurance, this is a great solution to get the medication you need to slow cognitive decline.
• Research studies offer protocols at no charge.  You will pay nothing.

How much does it cost?

The answer to that question is difficult to answer because there are so many factors to be considered. The Japanese drugmaker Eisai set the list price for Leqembi, at $26,500 per year in the United States. However, the actual cost for patients will vary depending on their insurance coverage. For example, Medicare beneficiaries are responsible for 20% of the cost after meeting their Part B deductible, which means the out-of-pocket cost for Medicare enrollees is $5,300 per year. Other factors that may affect the cost include Medicare supplemental or other secondary insurance, Medicare Advantage plans, and Medicaid. 

In addition to the cost of the drug itself, there are also associated expenses for diagnosing and monitoring patients, such as PET scans, MRI scans, and clinical visits. 

Is it worth it?

It is for my loved one.  Despite experiencing brain swelling and a brain bleed, she won’t stop as long as it is available.

I know that if I am diagnosed with mild cognitive impairment or Alzheimer’s disease, I would take it or a similar mAB as a multi-step treatment protocol.  I would work with an Alzheimer’s Disease researcher to be sure every bit of information is captured.

Is it worth it to you?  Only you can decide.