Donanemab got FDA approval on 2nd July 2024. The mechanism of action of Donanemab-azbt (Kisunla) is detailed here to understand how this new molecule can be a life-changer for people with Alzheimer’s disease.
Kisunla (Donanemab) is a special type of medicine known as a monoclonal antibody. Monoclonal antibodies are lab-made molecules designed to fight diseases like the body’s natural antibodies.
It specifically targets a type of protein called “insoluble N-truncated pyroglutamate amyloid beta.” These proteins can clump together in the brain and form plaques commonly found in people with Alzheimer’s disease.
This drug is made using a type of cell called a Chinese hamster ovary cell line, which is often used to produce biological medicines. The molecular weight of donanemab-azbt is about 145 kilodaltons (kDa), which gives an idea of the size of the molecule.
How is KISUNLA (donanemab-azbt) prepared and used?
KISUNLA is the brand name for the donanemab-azbt injection. This medication comes in a liquid form that is sterile (free from any germs) and does not contain any preservatives.
The solution can be clear or slightly cloudy, and its color can range from colorless to slightly yellow or brown.
The injection is provided in single-use vials, each containing 350 milligrams (mg) of the drug dissolved in 20 milliliters (mL) of liquid, which means the concentration is 17.5 mg of donanemab-azbt per mL.
Before being given to a patient, this solution must be diluted and then administered through an intravenous (IV) infusion, which means it is slowly injected into a vein.
What’s in the KISUNLA solution?
Each milliliter of the KISUNLA solution contains several ingredients:
- Donanemab-azbt: 17.5 mg, the active ingredient.
- Anhydrous citric acid: 0.32 mg, helps maintain the stability of the solution.
- Polysorbate 80: 0.20 mg, a substance that helps mix the ingredients properly.
- Sodium citrate: 2.15 mg, another stabilizing agent.
- Sucrose: 80 mg, a sugar that helps preserve the medicine.
- Water for Injection, USP: the solvent that dissolves all the ingredients.
The pH level of the solution, which indicates its acidity or alkalinity, is between 5.5 and 6.5.
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How does Donanemab-azbt work?
In Alzheimer’s disease, the brain accumulates clumps of a protein called amyloid beta, which form plaques. These plaques are thought to disrupt brain function and lead to the symptoms of Alzheimer’s, such as memory loss and cognitive decline.
Donanemab-azbt works by specifically binding to the amyloid beta plaques, particularly those that have undergone a modification called pyroglutamation.
By targeting these plaques, donanemab-azbt helps the body’s immune system to recognize and clear them away, potentially slowing the progression of Alzheimer’s disease.
Detailed Explanation of the Mechanism and Use of Donanemab-azbt:
Alzheimer’s disease is a progressive neurological disorder that affects millions of people worldwide. One of the key features of this disease is the accumulation of amyloid beta plaques in the brain.
These plaques are sticky clumps of protein that interfere with the normal function of brain cells, leading to their death and resulting in the symptoms associated with Alzheimer’s, such as memory loss, confusion, and changes in behavior.
Donanemab-azbt is designed to address this specific problem. The drug is a type of monoclonal antibody, which is a protein made in the lab that can bind to specific targets in the body.
In the case of donanemab-azbt, the target is the insoluble N-truncated pyroglutamate amyloid beta, a form of amyloid beta that is particularly prone to forming plaques.
When donanemab-azbt binds to these amyloid beta plaques, it flags them for destruction by the immune system. The immune cells then come in and break down these plaques, reducing their number in the brain.
This process can help to slow down the progression of Alzheimer’s disease by alleviating some of the damage caused by these plaques.
Production and Structure of Donanemab-azbt
The production of donanemab-azbt involves using a cell line derived from the Chinese hamster ovary (CHO) cells. These cells are commonly used in biotechnology for the production of therapeutic proteins because they can grow well in lab conditions and can produce proteins that are similar to those made naturally in human cells.
The donanemab-azbt protein is produced by these cells and then harvested and purified for use as a medication.
The molecular weight of donanemab-azbt is approximately 145 kDa. The molecular weight is a measure of the mass of the molecule, indicating its size and complexity [Ref].
For reference, this is much larger than most small-molecule drugs, which typically have molecular weights of less than 1 kDa. The large size of donanemab-azbt is characteristic of monoclonal antibodies, which are complex proteins.
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Preparation and Administration of KISUNLA
KISUNLA, the commercial name for donanemab-azbt, is supplied as a solution for injection. The solution is sterile, meaning it is free from any microorganisms, and preservative-free, meaning it does not contain substances that prevent the growth of bacteria or fungi.
The appearance of the solution can vary from clear to slightly cloudy, and its color can range from colorless to slightly yellow or brown.
The drug is provided in single-use vials containing 350 mg of donanemab-azbt in 20 mL of solution. This means each mL of the solution contains 17.5 mg of the drug.
Before being administered to a patient, this solution must be diluted with a suitable diluent and then given as an intravenous infusion.
An IV infusion is a method of administering medication directly into the bloodstream through a vein, which allows for quick and controlled delivery of the drug.
Ingredients in KISUNLA Solution
The solution contains several components in addition to the active ingredient, donanemab-azbt. Each mL of the solution includes:
- Anhydrous citric acid: This is a form of citric acid that does not contain water. It helps to maintain the stability and pH of the solution.
- Polysorbate 80: This is a surfactant that helps to keep the ingredients evenly mixed in the solution.
- Sodium citrate: This is a salt of citric acid that acts as a buffering agent to maintain the pH of the solution.
- Sucrose: This is a type of sugar that helps to preserve the stability of the protein.
- Water for Injection, USP: This is highly purified water used as the solvent for the solution.
The pH of the solution, which is a measure of how acidic or basic it is, ranges from 5.5 to 6.5. This range is close to neutral (7.0), making it relatively mild and suitable for injection.
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Clinical Use and Benefits of Donanemab-azbt:
The use of donanemab-azbt is primarily aimed at reducing the amyloid beta plaques in the brain of patients with Alzheimer’s disease.
By binding to these plaques and helping to clear them, the drug aims to slow down the progression of the disease.
This can potentially lead to improvements in symptoms or a slower decline in cognitive functions, offering hope for patients and their families.
Clinical studies have shown that donanemab-azbt can significantly reduce the levels of amyloid beta plaques in the brain.
This reduction is associated with a slower progression of Alzheimer’s symptoms, although the extent of the benefit can vary among patients. It’s important to note that while donanemab-azbt can help manage the symptoms of Alzheimer’s disease, it is not a cure. The disease can still progress, but potentially at a slower rate.
Conclusion
Donanemab-azbt represents a promising advancement in the treatment of Alzheimer’s disease. As a monoclonal antibody specifically designed to target and reduce amyloid beta plaques in the brain, it offers a targeted approach to managing this debilitating condition.
By understanding how this drug works, its preparation, and its clinical benefits, patients and healthcare providers can better appreciate the potential of donanemab-azbt in the fight against Alzheimer’s disease.