Leqembi Drug Information

LEQEMBI is indicated for the treatment of Alzheimer’s disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.

Patient Selection Confirm the presence of amyloid beta pathology prior to initiating treatment.

Recommended Dosage Initiate

LEQEMBI using a starting dosage regimen (see Table 1 ). After 18 months, the starting dosage regimen may be continued or a transition to a maintenance dosage regimen may be considered (see Table 2 ). Both the starting and maintenance dosage regimens can be administered by either intravenous infusion or subcutaneous injection.

The route of administration can be switched. When switching the route of administration and simultaneously transitioning from the starting dosage regimen to the maintenance dosage regimen, see Table 2. When switching the route of administration during the starting dosage regimen or during the maintenance dosage regimen, see Dosage and Administration.

Table 1: Starting Dosage Regimen For intravenous infusion, use LEQEMBI vials. LEQEMBI vials must be diluted before administration. For subcutaneous administration, use LEQEMBI IQLIK.

Switching Routes of Administration During the Starting Dosage Regimen or During the Maintenance Dosage Regimen During the starting dosage regimen and maintenance dosage regimen, the route of administration (intravenous with LEQEMBI vials or subcutaneous with LEQEMBI IQLIK) may be switched as described below. Thereafter follow the dosing schedule for the new route of administration. Switching Routes of Administration During the Starting Dosage Regimen • To switch from the intravenous to subcutaneous route of administration, administer the first subcutaneous dose 1 week after the last intravenous dose. • To switch from the subcutaneous to the intravenous route of administration, administer the first intravenous dose a minimum of 2 weeks, but no more than 3 weeks, after the last subcutaneous dose.

Monitoring and Dosing Interruption for Amyloid Related Imaging Abnormalities LEQEMBI can cause amyloid related imaging abnormalities -edema (ARIA-E) and -hemosiderin deposition (ARIA-H). Monitoring for ARIA Obtain a recent baseline brain magnetic resonance imaging (MRI) prior to initiating treatment with LEQEMBI. In general, the MRI should be performed within approximately one week before the next scheduled infusion or injection of LEQEMBI and reviewed prior to proceeding with the infusion or injection.

If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including an MRI if indicated. Recommendations for Dosing Interruptions in Patients with ARIA ARIA-E The recommendations for dosing interruptions for patients with ARIA-E are provided in Table 3. Table 3: Dosing Recommendations for Patients with ARIA-E: discomfort noticed, but no disruption of normal daily activity.

Severe: incapacitating, with inability to work or to perform normal daily activity. 2 See Table 5 for MRI radiographic severity. 3 Suspend until MRI demonstrates radiographic resolution and symptoms, if present, resolve; consider a follow-up MRI to assess for resolution 2 to 4 months after initial identification. ARIA-H The recommendations for dosing interruptions for patients with ARIA-H are provided in Table 4. Table 4: Dosing Recommendations for Patients with ARIA-H 1 See Table 5 for MRI radiographic severity. 2 Suspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; resumption of dosing should be guided by clinical judgment; consider a follow-up MRI to assess for stabilization 2 to 4 months after initial identification. 3 Suspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; use clinical judgment in considering whether to continue treatment or permanently discontinue LEQEMBI.

In patients who develop intracerebral hemorrhage greater than 1 cm in diameter during treatment with LEQEMBI, suspend dosing until MRI demonstrates radiographic stabilization and symptoms, if present, resolve.

Preparation and Administration of LEQEMBI for Intravenous Infusion Dilution Prior to intravenous administration, LEQEMBI must be diluted in 250 mL of 0.9% Sodium Chloride Injection, USP. Use aseptic technique when preparing the LEQEMBI diluted solution for intravenous infusion. Calculate the dose (mg), the total volume (mL) of LEQEMBI solution required, and the number of vials needed based on the patient’s actual body weight and the recommended dose of 10 mg/kg.

Each vial contains a LEQEMBI concentration of 100 mg/mL. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Check that the LEQEMBI solution is clear to opalescent and colorless to pale yellow.

Do not use if opaque particles, discoloration, or other foreign particles are present. Remove the flip-off cap from the vial. Insert the sterile syringe needle into the vial through the center of the rubber stopper.

Withdraw the required volume of LEQEMBI from the vial(s) and add to an infusion bag containing 250 mL of 0.9% Sodium Chloride Injection, USP. Each vial is for one-time use only. Discard any unused portion.

Gently invert the infusion bag containing the LEQEMBI diluted solution to mix completely. Do not shake. After dilution, immediate use is recommended.

If not administered immediately, store LEQEMBI 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. Administration Visually inspect the LEQEMBI diluted solution for particles or discoloration prior to administration.

Do not use if it is discolored, opaque, or foreign particles are seen. Prior to infusion, allow the LEQEMBI diluted solution to warm to room temperature. Infuse the entire volume of the LEQEMBI diluted solution intravenously over approximately one hour through an intravenous line containing a terminal low-protein binding 0.2 micron in-line filter.

Flush infusion line to ensure all LEQEMBI is administered. Monitor for any signs or symptoms of an infusion-related reaction during the infusion and consider longer periods of observation if clinically indicated. The infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy administered as clinically indicated.

Consider pre-medication at subsequent dosing with antihistamines, non-steroidal anti-inflammatory drugs, or corticosteroids.

Preparation and Administration of LEQEMBI IQLIK for Subcutaneous Injection Initiate therapy with LEQEMBI IQLIK under the guidance and supervision of a healthcare provider. LEQEMBI IQLIK may be administered by a patient or caregiver after the healthcare provider provides direct guidance for at least 2 consecutive subcutaneous doses, and determines that administration of LEQEMBI IQLIK by the patient or caregiver is appropriate. Selection for Administration by the Patient or Caregiver Base selection of patients and caregivers who are capable of administration of LEQEMBI IQLIK on: 1.

The patient and/or caregiver’s ability to perform subcutaneous injections with the LEQEMBI IQLIK autoinjector with proper technique according to the prescribed dosing regimen. 2. The patient and/or caregiver’s ability to recognize and manage symptoms of a hypersensitivity reaction, such as anaphylaxis. The healthcare provider should periodically re-assess the appropriateness of administration of LEQEMBI IQLIK by the patient or caregiver on an ongoing basis.

Instruct patients and/or caregivers on the proper subcutaneous administration of LEQEMBI IQLIK. Direct patients and/or caregivers to follow the directions provided in the Instructions for Use for additional details on administration. Preparation and Administration • Before injection, remove LEQEMBI IQLIK from the refrigerator and leave at room temperature for 20 minutes.

Do not use an external heat source to heat LEQEMBI IQLIK because heat may damage the product. • Do not shake LEQEMBI IQLIK. • Visually inspect LEQEMBI IQLIK for particles or discoloration prior to administration. The solution should be a clear to opalescent, colorless to pale yellow solution, and free of visible particles. Do not use LEQEMBI IQLIK if it is cloudy or there are visible particles. • Do not use LEQEMBI IQLIK if it looks damaged or has been dropped. • Sites for injection include the abdomen or upper thigh.

The back of the upper arm can also be used as an injection site if healthcare provider or caregiver administers the injection. • Rotate injection sites and administer at least 1 inch from the previous injection. • Do not inject into moles, scars, bruises, tattoos or into areas where the skin is red, hard, tender or injured. • Do not inject into the 2-inch area around the navel. • Monitor for signs or symptoms of an injection reaction.

Missed Dose Intravenous Infusion If a starting dosage or maintenance dosage infusion is missed, administer the next dose as soon as possible. Subcutaneous Injection If a scheduled dose of the subcutaneous starting or maintenance dosing regimen is missed, administer LEQEMBI IQLIK as soon as possible, up to 6 days after the missed dose, and then administer the next dose on the regularly scheduled day. Thereafter, resume the original dosing schedule.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials with Intravenous Administration The safety of LEQEMBI has been evaluated in 2090 patients who received at least one dose of LEQEMBI by intravenous infusion. The mean age at study entry was 72 years (range from 50 to 90 years).

In the double-blind, placebo-controlled period in Study 1, patients stopped study treatment because of an adverse reaction in 15% of patients treated with LEQEMBI, compared to 6% patients on placebo; in Study 2, patients stopped study treatment because of an adverse reaction in 7% of patients treated with LEQEMBI, compared to 3% patients on placebo. Table 7: Adverse Reactions Reported in at Least 5% of Patients Treated with LEQEMBI 10 mg/kg Every Two Weeks and at least 2% Higher than Placebo in Study Rash includes acne, erythema, infusion site rash, injection site rash, rash, rash erythematous, rash pruritic, skin reactions, and urticaria. Less Common Adverse Reactions Atrial fibrillation occurred in 3% of patients treated with LEQEMBI, compared to 2% in patients on placebo.

In Study 1, lymphopenia or decreased lymphocyte count was reported in 4% of patients treated with LEQEMBI after the first dose, compared to less than 1% of patients on placebo; lymphocytes were not measured after the first dose in Study 2. Clinical Trials with Subcutaneous Administration The safety of LEQEMBI for subcutaneous administration once every week was evaluated in open-label studies in 424 patients. The overall safety profile in these patients was similar to that observed in patients who received LEQEMBI by intravenous infusion in Study 1 and Study 2.

Injection-related reactions were observed in patients who received LEQEMBI subcutaneously, most of which were localized reactions; systemic reactions were less frequently observed. The majority of injection-related reactions occurred at the time of the first dose when initiating therapy. Recurrent localized injection-related reactions and/or delayed reactions occurring up to several days after an injection, were also observed.

Localized injection-related reactions included erythema, induration, swelling, heat, pain, pruritus, rash, ecchymosis, nodule, and hematoma. Systemic injection-related reactions presented with symptoms of headache, chills, fever, and fatigue. Severe localized injection-related reactions and localized injection-related reactions leading to discontinuation or interruption of subcutaneous LEQEMBI did occur.

Pregnancy Risk Summary There are no adequate data on LEQEMBI use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. No animal studies have been conducted to assess the potential reproductive or developmental toxicity of LEQEMBI. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

The background risk of major birth defects and miscarriage for the indicated population is unknown.

Pediatric Use Safety and effectiveness of LEQEMBI in pediatric patients have not been established.

LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients. Reactions have included angioedema and anaphylaxis.