Aducanumab - First FDA-Approved Therapy for Treating Alzheimer’s Disease

What Is Aducanumab?

Aducanumab is considered a major development because it is the first treatment designed to slow the progression of Alzheimer’s disease rather than only treating symptoms. Alzheimer’s develops due to many complex changes in the brain, so treatments need to work on more than one problem.

Even with progress in research, a complete cure for Alzheimer’s disease is still not available. Most current treatments only help manage symptoms and do not address the root cause of the disease.

Is Aducanumab FDA-Approved?

Aducanumab is FDA-approved. Instead of merely reducing symptoms, Aducanumab aims to prevent the progression of the condition by decreasing protein deposits in the brain. This makes it the first drug to be FDA-approved that targets the way Alzheimer’s disease progresses.

How Does Aducanumab Work?

This drug works by activating the immune system to break down beta-amyloid plaque (harmful protein deposits) that damage brain cells and cause mental decline. Although Aducanumab reduces amyloid plaque, it does not cure Alzheimer’s disease or stop disease progression.

Current evidence has clearly not shown that it slows cognitive decline, such as memory loss, confusion, difficulty managing daily activities, repeated questioning, or changes in personality and behavior.

Uses:

• Alzheimer’s Disease: Aducanumab is used to reduce amyloid-beta plaques in the brain.

• Cognitive Impairment: Aducanumab is indicated for people with mild cognitive impairment (problems with memory or thinking).

Dosage:

• This drug is indicated for the treatment of Alzheimer's disease and is administered as an intravenous infusion (directly into the vein) every four weeks, with at least 21 days between infusions.

Dose Schedule:

• Infusions 1 to 2: 1 mg/kg IV every four weeks.

• Infusions 3 to 4: 3 mg/kg IV every four weeks.

• Infusions 5 to 6: 6 mg/kg IV every four weeks.

• Infusion 7 Onward: 10 mg/kg IV every four weeks.

For Patients

Learn More About Aducanumab

Before Starting Aducanumab:

• Patients should discuss their allergies to Aducanumab, any other medications, or any components of Aducanumab with their physician.

• The pharmacist may be consulted for awareness about the ingredients of the medication.

• It is also necessary to inform the doctor about other medications used. Adjustments may be needed for proper dosages of medications to avoid interactions.

• The patient should also inform the doctor about any medical conditions they might be having.

• Pregnant women, women planning to become pregnant, as well as lactating mothers, should consult their doctors before treatment.

How Effective Is Aducanumab?

Aducanumab effectiveness has been a topic of debate. The FDA approved the drug through a special fast-track used for serious illnesses based on a clinical benefit. Instead of proving clear improvement in memory or thinking, the approval was based on the drug’s ability to reduce amyloid beta plaques in the brain, which are linked to Alzheimer’s disease.

Clinical trials of Aducanumab have shown mixed results in terms of its effectiveness. Clinical trials did not show clear benefits, but in one study, a group of patients who received the highest dose for a longer time showed slower mental decline compared to those who received a placebo.

Important Points Before Starting Aducanumab:

• Medical History: Past and current disease conditions should be discussed, along with current medications.

• Potential Risks and Benefits: Consider the potential benefits against the possible risks, including serious side effects like brain swelling, bleeding, or allergic reactions.

• Clinical Trial Results: The results of Aducanumab clinical trials should be reviewed with the doctor, including how the studies were conducted, who participated in them, and what the findings showed.

• Brain Imaging: Brain scans should be done on a regular basis to monitor changes or abnormalities in response to treatment.

• Other Treatments Might Be Considered: Lifestyle modifications, other medications, and alternative therapies that may help support the care.

How to Take Aducanumab?

• Aducanumab is administered through an intravenous (IV) infusion that usually takes 45 to 60 minutes.

• The infusion is done at a hospital or infusion center by trained healthcare professionals.

• Before starting, doctors may perform tests to ensure the treatment is safe.

• The patient is closely observed during the infusion for any side effects, and may remain under observation for a short period afterward.

• Aducanumab is typically given once every four weeks.

What Are the Precautions to Take After Starting Aducanumab?

After starting Aducanumab, there are several important steps to follow to get the best results and reduce the risk of side effects.

• Go to all follow-up visits so the doctor can see how the medicine is working.

• Tell the doctor right away if there are side effects like headache, confusion, or falls.

• Keep taking other Alzheimer’s treatments along with Aducanumab.

• Stay active by reading, doing puzzles, and moving your body to keep your brain healthy.

• Eat healthy foods to support your body and brain.

• Write down any changes you notice so you and your doctor can track progress.

What Are the Side Effects of Aducanumab Therapy?

Aducanumab can cause ARIA (amyloid-related imaging abnormalities).

Other Side Effects:

• Headache, diarrhea, confusion, or delirium.

• Falls, altered mental status, or disorientation.

• Hypersensitivity or immune reactions.

• Slight increases in liver enzymes have been observed, though no liver damage has been reported.

For Doctors

Indication:

• Aducanumab is a medicine approved to help people with Alzheimer’s disease, but only those in the early stages, like mild memory problems or mild dementia. It is not meant for everyone with Alzheimer’s.

• Studies showed that the drug can reduce sticky protein clumps in the brain called amyloid. Because of this, the FDA gave it special approval in 2021, but there was debate about how much it really helps people, and some experts disagreed.

• Most dementia cases in people over 65 are caused by Alzheimer’s disease, and it is a major cause of death in the U.S.

• Alzheimer’s happens slowly when harmful proteins build up in the brain, damaging brain cells. Over time, this affects memory, thinking, language, and behavior.

• Right now, there is no cure for Alzheimer’s. Available medicines only help manage symptoms and do not stop the disease completely.

Pharmacology:

The amyloid theory says that Alzheimer’s disease may happen because amyloid-beta proteins build up in the brain.

Aducanumab is a laboratory-made antibody that finds these harmful amyloid clumps and helps break them down into smaller, safer pieces. It mainly targets amyloid in brain tissue and not in blood vessels.

The U.S. FDA now recommends using aducanumab only for people with early Alzheimer’s, such as those with mild memory problems or mild dementia.

Mechanism of Action:

Aducanumab is a monoclonal antibody belonging to the human immunoglobulin gamma 1 (IgG1) class and is categorized as an immunotherapeutic agent.

Its targeted action results in a reduction of amyloid beta (Aβ) plaques in the brain, along with a decrease in phosphorylated tau levels seen in the cerebrospinal fluid and a reduction in medial temporal neurofibrillary tangles observed on tau PET (positron emission tomography) imaging in a small subset of patients.

Pharmacodynamics:

• Absorption: Aducanumab should be given monthly as an intravenous infusion at a dose of 10 mg/kg. Aducanumab is absorbed and reaches a peak concentration (Cmax) of 182.7 μg/mL after 3.0 hours, with an area under the curve (AUCinf) of 31,400 h∗μg/mL.

• Metabolism: Aducanumab is metabolized into smaller oligopeptides and amino acids for elimination. The mean clearance of Aducanumab is 0.0159 L/h, and its terminal half-life is 24.8 days.

• Elimination: Aducanumab is metabolized into smaller oligopeptides and amino acids for elimination, with a mean clearance of 0.0159 L/h and a terminal half-life of 24.8 days.

Warnings and Precautions

Amyloid-related imaging abnormalities (ARIA) may occur with Aducanumab treatment. Usually temporary and often resolves on its own.

Types of ARIA:

• ARIA-E: Swelling in the brain (edema).

• ARIA-H: Small brain bleeds and surface iron deposits seen on MRI.

Possible Symptoms of ARIA:

• Headache.

• Confusion.

• Dizziness.

• Seizures.

• Vision changes.

• Nausea.

Most commonly seen during the first eight doses, especially during dose titration.

Monitoring:

• Enhanced clinical and MRI (magnetic resonance imaging) monitoring is recommended.

• Dosing recommendations for patients with ARIA-E depend on the severity of clinical symptoms and radiographic findings.

• Dosing recommendations for patients with ARIA-H depend on the type and severity of radiographic findings.

• In cases of recurrent ARIA-E, clinical judgment should be used to determine whether to continue dosing.

• It is recommended to have periodic monitoring with an MRI and a brain MRI.

• If a patient experiences symptoms suggestive of ARIA, clinical evaluation, including MRI if necessary, should be performed.

• If amyloid-related imaging abnormalities are observed on MRI, a careful clinical examination and evaluation need to be conducted before continuing treatment.

Dosage Strength and Forms:

• First Infusion: 1 mg/kg.

• Second Infusion: 1 mg/kg.

• Third Infusion: 3 mg/kg.

• Fourth Infusion: 3 mg/kg.

• Fifth Infusion: 6 mg/kg.

• Sixth Infusion: 6 mg/kg.

• Seventh Infusion Onwards: 10 mg/kg.

Dosage and Administration

• Aducanumab solution is a colorless to yellow, clear to opalescent liquid supplied in single-dose vials for intravenous infusion.

• Before infusion, Aducanumab should be diluted according to the subject’s body weight.

• Prepare 100 mL of 0.9 % sodium chloride injection for dilution.

• The diluted solution should be allowed to settle at room temperature and administered promptly.

• Any remaining solution should be discarded.

• Aducanumab is available in single doses of: 170 mg/1.7 mL (100 mg/mL) or 300 mg/3 mL (100 mg/mL)

• The dose should be gradually increased to 10 mg/kg by the seventh infusion.

• Each infusion is given every four weeks, with a minimum of 21 days between infusions.

Considerations for Administration:

There are no known contraindications for Aducanumab. Additionally, no drug-drug interactions have been reported thus far. During pivotal trials, conventional therapy for Alzheimer's disease was used, and Aducanumab can be used in conjunction with other medications used to manage the disease.

Drug Interactions:

• Limited data are available on the potential drug interactions of Aducanumab.

• As a monoclonal antibody administered through intravenous infusion, it is not expected to have significant drug interactions with other medications.

• However, caution should be exercised when administering Aducanumab with other medications that affect the immune system or those that have potential neurotoxic effects.

• Co-administration of Aducanumab with other biologic therapies or immunosuppressants may increase the risk of infections. Vaccinations with live attenuated vaccines should be avoided while on Aducanumab therapy.

Other Specifications:

• Pregnancy: There is limited information on the use of Aducanumab during pregnancy. Potential risks to the mother or fetus, including birth defects or miscarriage, are not known.

• Lactation: The data on whether Aducanumab passes into human breast milk or affects breastfed infants or milk production are not available. Based on studies of similar monoclonal antibodies, transfer into breast milk is expected to be low, but the clinical significance of this exposure is unknown.

• Geriatric Use: Aducanumab is intended for use in older adults with Alzheimer’s disease. Clinical studies have included patients with mild cognitive impairment or mild dementia. As Alzheimer’s disease mainly affects elderly individuals, this group represents the primary population for treatment.