Leqembi

Leqembi (lecanemab) is a monoclonal antibody used to treat Alzheimer’s disease to help slow the decline in memory, thinking, and behavior in patients who have mild cognitive impairment (MCI) or mild dementia. Leqembi works by targeting and removing amyloid‑beta protein plaques from the brain, which helps slow the progression of dementia symptoms. Leqembi is an amyloid beta-directed antibody against aggregated soluble and insoluble forms of amyloid beta.

Leqembi can be self-administered once a week as an injection under the skin (subcutaneous injection) using the Leqembi Iqlik autoinjector, after training and once your healthcare provider decides it is appropriate. After 18 months of treatment, the dose may be reduced from 500 mg to 360 mg a week.

Leqembi can also be administered as an intravenous infusion (IV) every 2 weeks, which takes approximately one hour. After 18 months of treatment, infusions may change to every 4 weeks.

In the clinical trial Clarity AD (NCT03887455), Leqembi slowed cognitive decline by 27% over 18 months compared to placebo. This was measured using the global cognitive and functional scale (CDR-SB).

Leqembi helps to slow the progression of Alzheimer’s disease but does not cure it.

Leqembi's FDA approval is to treat Alzheimer's disease in patients who have:

• mild cognitive impairment or mild dementia due to Alzheimer's disease, and
• presence of amyloid beta pathology.

Leqembi's FDA approval was first granted on January 6, 2023, to Biogen Inc. and Eisai Co. Ltd.

For information on Leqembi's effectiveness, see How effective is Leqembi in delaying Alzheimer's disease?

Leqembi works against amyloid beta in two related ways:

• Binds clumped amyloid beta: Leqembi attaches to aggregated (clumped) forms of amyloid beta, including both soluble clumps and the insoluble deposits found in plaques.
• Helps reduce plaques: By binding these clumped forms, Leqembi helps the body clear amyloid and lower the amount of plaque in the brain.

Reducing amyloid beta plaque is how Leqembi helps slow the decline in memory, thinking, and behavior in Alzheimer's disease.

Leqembi's mechanism of action is as an amyloid beta-directed antibody against aggregated soluble and insoluble forms of amyloid beta.

Why is amyloid important in Alzheimer’s disease?

Alzheimer’s disease is a form of dementia that affects memory, thinking, and behavior. Over time, it can interfere with daily activities. One of the causes of Alzheimer’s disease is thought to be abnormal buildup in the brain of a protein (amyloid) into clumps or plaques, which makes it harder for brain cells to communicate with each other and results in the symptoms of Alzheimer’s disease.

Leqembi can be given as an infusion into a vein or as an injection under the skin, depending on which formulation you are prescribed.

Subcutaneous injection (Leqembi Iqlik)

Leqembi Iqlik is injected under the skin (subcutaneously) into the front of the thighs or the stomach area (abdomen). You or a caregiver can give the injection once your healthcare provider decides you are ready, which happens after you have received at least 2 doses in a row under their direct supervision. A healthcare provider or caregiver may also inject into the back of the upper arm.

Before injecting at home, read the Instructions for Use supplied with Leqembi Iqlik so you know how to prepare and give each dose correctly. Your healthcare provider will demonstrate the technique and tell you how often to inject. Always use it exactly as directed.

When choosing where to inject:

• Rotate injection sites, keeping each new site at least 1 inch away from the previous one.
• Avoid the 2-inch area surrounding the belly button.
• Never inject into moles, scars, bruises, tattoos, or skin that is red, hard, tender, or damaged.

If you miss a dose of Leqembi Iqlik, inject it as soon as you can, up to 6 days after the missed dose. Then carry on with your next injection on your usual scheduled day.

Intravenous (IV) infusion

Leqembi IV is administered by a healthcare provider through a needle inserted into a vein in your arm. Each infusion takes around 1 hour to complete, and your healthcare provider will let you know how often your doses are scheduled. If you miss an infusion, arrange to have your next dose as soon as possible.

Do not receive this medicine if you are allergic to the active ingredient lecanemab or any of the inactive ingredients in this medicine. See below for a list of inactive ingredients.

Tell your healthcare provider about all of your medical conditions.

Pregnancy

It is not known if this medicine will harm your unborn baby. Tell your healthcare provider if you become pregnant during Leqembi treatment.

Breastfeeding

It is not known if Leqembi passes into breast milk. Talk to your healthcare provider about the best way to feed your baby while receiving this medicine.

Serious side effects and warnings

Boxed Warning for Amyloid-related imaging abnormalities

Leqembi has a boxed warning for amyloid-related imaging abnormalities or “ARIA”. A boxed warning is the strongest safety-related warning issued by the FDA.

This medicine can cause a condition called ARIA, which does not usually cause any symptoms; however serious and life-threatening events can occur, which can be fatal. ARIA is most commonly seen as temporary swelling in areas of the brain that usually resolve over time. Some people may also have small spots of bleeding in or on the surface of the brain, and infrequently, larger areas of bleeding in the brain can occur. Most people with this type of swelling in the brain do not have symptoms; however, some people may have symptoms, such as headache, confusion, dizziness, vision changes, nausea, difficulty walking, seizures, difficulty speaking, or muscle weakness. Seek medical help immediately if you have any of these symptoms.

Some people have a genetic risk factor (ApoE ε4 homozygotes) that may cause an increased risk for ARIA. Talk to your healthcare provider about testing to see if you have this risk factor.

Some medicines can increase the risk for larger areas of bleeding in the brain in patients taking this medicine. Talk to your healthcare provider to see if you are on any medicines that increase this risk.

Your healthcare provider will do magnetic resonance imaging (MRI) scans before and during your treatment with this medicine to check you for ARIA. Call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the symptoms listed above.

You should carry information that you are receiving Leqembi which can cause ARIA and that ARIA symptoms can look like stroke symptoms.

There are registries that collect information on treatments for Alzheimer's disease. Your healthcare provider can help you become enrolled in these registries. For more information, call Eisai at 1-888-274-2378.

Serious allergic reactions

Swelling of the face, lips, mouth, or tongue, hives, or difficulty breathing have happened during treatment with Leqembi. Tell your healthcare provider and get medical help right away if you have any symptoms of a serious allergic reaction during or after treatment with Leqembi.

Infusion-related reactions

Infusion-related reactions are a common side effect that can be serious. Most infusion-related reactions happen with the first infusion, but they can occur with any infusion. Symptoms can happen during the infusion or after you leave the infusion center. Infusion-related reactions occurred in 26% of Leqembi patients compared to 7% of placebo patients in the Clarity AD (Study 2 NCT03887455). Symptoms of infusion reactions are:

• fever
• flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain),
• nausea and vomiting,
• low blood pressure (hypotension),
• high blood pressure (hypertension),
• oxygen desaturation (difficulty breathing or shortness of breath), dizziness or lightheadedness, and changes in your heart rate or feeling like your chest is pounding.

Managing infusion-related reactions. If you have an infusion-related reaction, the infusion rate may be reduced, or the infusion may be stopped, and appropriate therapy may be started as clinically indicated. Before future infusions, preventative (prophylactic) treatment with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids may be considered.

Common Leqembi side effects

The most common side effects of Leqembi are:

• headache
• infusion-related reactions, which can be serious
• swelling in areas of the brain, with or without small bleeding spots in or on the brain's surface (ARIA).

The most common side effects occurred in 10% or more of patients and were higher than the side effect incidence compared to placebo.

Injection-related reactions. If you receive Leqembi Iqlik as an injection under the skin (subcutaneous injection), you may have a reaction at the injection site. This can include redness (erythema), a hard lump or firmness (induration), swelling, warmth, rash, pain, itching, bruising (ecchymosis), and a collection of blood under the skin (hematoma). Some people may also have symptoms such as headache, chills, fever, and tiredness (fatigue). Tell your healthcare provider if you have any of these reactions during or after your injection.

These are not all the possible side effects of Leqembi. For more information, ask your healthcare provider or pharmacist, or see below for more detailed information on side effects. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The recommended starting dose of Leqembi depends on how it is given:

• Subcutaneous injection: 500 mg (two 250 mg injections) once a week, given under the skin using the Leqembi Iqlik autoinjector.
• Intravenous (IV) infusion: 10 mg/kg once every 2 weeks. The dose is diluted first and then infused into a vein over approximately 1 hour.

After 18 months of treatment, you may either continue on the starting dose or move to a maintenance dose, which can be given intravenously or subcutaneously.

The recommended maintenance dose is:

• Subcutaneous injection: 360 mg once a week using the Leqembi Iqlik autoinjector.
• Intravenous (IV) infusion: 10 mg/kg once every 4 weeks.

Before and during treatment

• Your healthcare provider will confirm you have amyloid beta pathology (a buildup of amyloid protein in the brain) before starting Leqembi.
• A recent baseline brain MRI is needed before treatment begins.
• Follow-up MRIs are done after 1, 2, 3, and 6 months of treatment to monitor for ARIA (amyloid-related imaging abnormalities). If ARIA is seen on an MRI, decisions about continuing, pausing, or stopping treatment depend on the type of ARIA, how severe it is, and whether you have symptoms.

Subcutaneous injection

Leqembi Iqlik is a single-dose prefilled autoinjector available in two strengths:

• 250 mg/1.25 mL (200 mg/mL)
• 360 mg/1.8 mL (200 mg/mL)

Intravenous infusion

Leqembi for IV infusion is a single-dose vial available in two strengths:

• 200 mg/2 mL (100 mg/mL)
• 500 mg/5 mL (100 mg/mL)

Review the Leqembi Package Insert (PI) for more detailed information about this medicine. The PI contains more comprehensive information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interaction, and more. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

The Package Insert is sometimes called the Prescribing Information (PI) or the FDA label.

Tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.

Especially tell your healthcare provider if you take medicines to reduce blood clots from forming (antithrombotic medicines, including aspirin). Ask your healthcare provider for a list of these medicines if you are not sure.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Leqembi IQLIK Storage

• Store Leqembi IQLIK autoinjectors in a refrigerator between 36°F to 46°F (2°C to 8°C).
• Do not freeze.
• Keep the Leqembi IQLIK autoinjector in the original package until ready to use, to protect from light.
• Leqembi IQLIK may be stored at room temperature up to 77°F (25°C) for up to 14 days in the original package.

Do not place it back in the refrigerator if it has been brought to room temperature.

• Do not shake Leqembi IQLIK.
• Throw away (dispose of) Leqembi IQLIK that is out of date, or if it is not stored the right way.

Keep out of the reach of children.

Leqembi for Intravenous Infusion Storage

Unopened Vial Storage:

• Store in a refrigerator at 2°C to 8°C (36°F to 46°F).
• Store in the original carton to protect from light.
• Do not freeze or shake.

After vial dilution

• Immediate use is recommended
• If not administered immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 4 hours, or at room temperature up to 30°C (86°F) for up to 4 hours.
• Do not freeze.

Leqembi and Leqembi Iqlik are manufactured by Eisai Inc., Nutley, NJ 07110.

Active ingredient: lecanemab-irmb.

Inactive ingredients (intravenous): arginine hydrochloride, histidine, histidine hydrochloride monohydrate, polysorbate 80, and water for injection.

Inactive ingredients (subcutaneous): arginine hydrochloride, histidine, histidine hydrochloride monohydrate, polysorbate 80, and water for injection.