Leqembi

Treatment for Early Alzheimer's Disease

Leqembi is specifically indicated for patients in the early stages of Alzheimer's disease. This includes individuals experiencing:

• Mild cognitive impairment (MCI): A condition where memory or thinking problems are more frequent than normal for a person's age, but do not yet significantly interfere with daily life.
• Mild dementia: The early stage of Alzheimer's where symptoms begin to impact some daily activities.

Requirements for Use

Before starting treatment, healthcare providers must confirm the presence of amyloid beta plaques in the brain. This is a hallmark of Alzheimer's disease and is typically verified through specialized testing, such as:

• A positron emission tomography (PET) scan of the brain.
• A lumbar puncture to test cerebrospinal fluid.

Goals of Therapy

The primary goal of Leqembi is to slow the clinical decline associated with Alzheimer's disease. By targeting the underlying biology of the disease, the medication aims to help patients maintain their cognitive and functional abilities—such as memory, orientation, and the ability to perform daily tasks—for a longer period than they might without the treatment.

Limitations of Use

Leqembi is not a cure for Alzheimer's disease and cannot reverse existing brain damage. It has not been studied in, and is not currently intended for, patients in the more advanced stages of the disease or those who do not yet show symptoms. There is no evidence that the drug is effective for other types of dementia not caused by Alzheimer's disease.

Targeting Amyloid Plaques

Leqembi belongs to a class of medications known as monoclonal antibodies. In individuals with Alzheimer's disease, a protein called amyloid-beta clumps together to form plaques between neurons in the brain. These plaques are believed to disrupt communication between brain cells and contribute to the progression of the disease.

This medication is specifically designed to identify and bind to these amyloid-beta clusters, particularly the intermediate forms known as protofibrils. Once the drug attaches to these clusters, it assists the body's immune system in recognizing and clearing the protein buildup from the brain tissue.

Slowing Disease Progression

By reducing the accumulation of amyloid-beta plaques, Leqembi aims to slow down the cognitive and functional decline associated with Alzheimer's. Clinical evidence suggests that removing these plaques can help delay the worsening of symptoms such as memory loss and confusion.

It is important to note that Leqembi is intended for patients in the early stages of the disease, including those with mild cognitive impairment or mild dementia, who have confirmed evidence of amyloid plaques. The treatment is not a cure and does not reverse existing brain damage or restore memory that has already been lost.

Common Side Effects

The most frequently reported side effects of Leqembi include:

• Infusion-related reactions: These typically occur during or shortly after the treatment, most commonly with the first dose. Symptoms may include fever, chills, headache, nausea, vomiting, and changes in blood pressure.
• Headache: This is a common symptom reported by many patients during treatment.
• Cough: Some individuals may experience a persistent cough.
• Diarrhea: Digestive upset is a possible side effect.

Serious Side Effects

The most significant concern with Leqembi is a condition called Amyloid-Related Imaging Abnormalities (ARIA). ARIA is a side effect that affects the brain and is usually identified through medical imaging.

Amyloid-Related Imaging Abnormalities (ARIA)

ARIA involves temporary swelling in areas of the brain or small spots of bleeding on the brain's surface. While many people do not have symptoms, ARIA can occasionally be serious or life-threatening. Symptoms of ARIA may include:

• Severe or persistent headache
• Confusion or disorientation
• Dizziness
• Vision changes
• Nausea
• Seizures
• Difficulty walking

Because of the risk of ARIA, healthcare providers require regular MRI scans to monitor the brain before starting treatment and at specific intervals during the first several months of therapy. Certain factors, such as carrying the ApoE ε4 gene or taking blood-thinning medications, may increase the risk of serious complications from ARIA.

Infusion Reactions

In addition to flu-like symptoms, infusion reactions can sometimes involve more significant symptoms like skin rash, joint pain, or shortness of breath. Healthcare providers may monitor patients closely during the infusion and may provide medications beforehand to help reduce the risk of these reactions.

Amyloid-Related Imaging Abnormalities (ARIA)

Leqembi can cause amyloid-related imaging abnormalities, known as ARIA. This condition most commonly involves temporary swelling in areas of the brain (ARIA-E) or small spots of bleeding on the surface of the brain (ARIA-H). While many cases do not cause symptoms, some can be serious or life-threatening.

Symptoms of ARIA may include:

• Headache
• Confusion or disorientation
• Dizziness
• Vision changes
• Nausea
• Seizures

Genetic Risk Factors

Patients who have two copies of the ApoE ε4 allele have a higher risk of developing ARIA compared to those with one or no copies. Healthcare providers typically recommend genetic testing for this marker before starting treatment to help assess the risk of brain swelling and bleeding.

MRI Monitoring Requirements

Because ARIA often occurs without noticeable symptoms, regular brain monitoring is required. MRI scans are typically scheduled at the following intervals:

• Before starting the first dose (baseline).
• Before the 5th, 7th, and 14th infusions.

If ARIA is detected on an MRI, treatment may need to be paused or permanently discontinued depending on the severity of the findings and whether the patient is experiencing symptoms.

Infusion-Related Reactions

Some patients experience reactions during or shortly after the infusion. Common symptoms include fever, chills, body aches, nausea, and changes in blood pressure. Healthcare providers may use medications such as acetaminophen or antihistamines before the infusion to help reduce the likelihood of these reactions.

Use with Blood Thinners

The use of Leqembi alongside anticoagulant medications (blood thinners) may increase the risk of larger brain bleeds. Caution is advised when considering Leqembi for patients who require these medications or who have other risk factors for brain hemorrhage.

Contraindications

Leqembi should not be used by individuals with a known serious hypersensitivity to lecanemab or any of the inactive ingredients in the medication. Serious allergic reactions, such as angioedema or anaphylaxis, have been reported.

Pregnancy

It is not known if Leqembi will harm an unborn baby. There are no adequate clinical studies evaluating the use of this medication in pregnant individuals. If you are pregnant or planning to become pregnant, it is important to discuss the potential risks and benefits with your healthcare provider before starting or continuing treatment.

Breastfeeding

Researchers do not yet know if Leqembi passes into human breast milk or how it might affect a nursing infant. Because the safety of the drug during lactation has not been established, individuals who are breastfeeding or planning to breastfeed should consult their doctor to determine the best course of action for their specific situation.

Dosage Forms

Leqembi is supplied in the following form:

• Intravenous Solution: A liquid solution provided in single-dose vials for administration into a vein.

Administration

This medication is administered as an intravenous infusion by a healthcare provider. It is not available in oral forms such as tablets or capsules.

FDA Approval Status

Leqembi received traditional approval from the U.S. Food and Drug Administration (FDA) in July 2023. This followed an initial accelerated approval granted in January 2023. It is indicated for patients with Alzheimer’s disease who have mild cognitive impairment or mild dementia, which are the stages of the disease studied in clinical trials.

Boxed Warning and Safety Monitoring

The medication carries a Boxed Warning regarding Amyloid-Related Imaging Abnormalities (ARIA). ARIA most commonly presents as temporary swelling in areas of the brain (ARIA-E) or small spots of bleeding on the surface of the brain (ARIA-H). While often asymptomatic, these conditions can occasionally be serious or life-threatening.

To manage these risks, the FDA requires or recommends the following:

• MRI Monitoring: Patients must have a baseline brain MRI before starting treatment. Follow-up MRIs are required before the 5th, 7th, and 14th infusions to check for ARIA.
• Genetic Testing: Healthcare providers are encouraged to test patients for the ApoE ε4 gene. Individuals with two copies of this gene (homozygotes) have a significantly higher risk of developing ARIA compared to those with one or no copies.
• Clinical Vigilance: Doctors must monitor for symptoms such as headache, confusion, dizziness, vision changes, or seizures, which may indicate ARIA.

Usage Limitations

There is currently no safety or efficacy data on starting treatment at earlier or later stages of Alzheimer's disease than those studied. The FDA notes that treatment should only be initiated in patients with confirmed amyloid pathology in the brain.

Estimated Annual Cost

The manufacturer's list price for Leqembi is approximately $26,500 per year. This figure represents the cost of the medication itself and does not include the expenses associated with its administration or the medical monitoring required during treatment.

Insurance and Medicare Coverage

Medicare provides coverage for Leqembi for patients with a diagnosis of mild cognitive impairment or mild Alzheimer's disease dementia. To qualify for coverage, the prescribing physician and clinical team must participate in a qualifying registry to track the drug's safety and effectiveness. Under standard Medicare Part B rules, patients are typically responsible for a 20% coinsurance payment after meeting their deductible, though supplemental insurance may cover some of these costs.

Private insurance coverage varies by provider and specific plan. Many insurers require prior authorization and objective evidence of amyloid plaques in the brain before approving coverage for the medication.

Additional Treatment Expenses

The total cost of care involves several medical services that are not included in the drug's list price:

• Infusion Services: Leqembi is administered as an intravenous infusion every two weeks, which incurs costs for the facility and the healthcare professionals who manage the infusion.
• Diagnostic Testing: Before starting treatment, patients must undergo diagnostic tests, such as a PET scan or cerebrospinal fluid analysis, to confirm the presence of amyloid plaques.
• Monitoring Scans: The FDA requires multiple MRI scans, particularly during the first year of treatment, to monitor for potential side effects such as brain swelling or small bleeds.
• Neurological Evaluations: Regular follow-up appointments with specialists are necessary to monitor the progression of the disease and the safety of the treatment.