Lecanemab

Prescription

Tên thương mại: LEQEMBI, LECANEMAB AUTOINJECTOR

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Injection

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INTRAVENOUS

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Eisai Inc.

About This Medication

11 DESCRIPTION Lecanemab-irmb is a recombinant humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta, and is expressed in a Chinese hamster ovary cell line. Lecanemab-irmb has an approximate molecular weight of 150 kDa. LEQEMBI Injection for Intravenous Use LEQEMBI (lecanemab-irmb) injection is a sterile, preservative-free, clear to opalescent and colorless to pale yellow solution for intravenous infusion after dilution. LEQEMBI is supplied in single-dose vials available in concentrations of 500 mg/5 mL (100 mg/mL) or 200 mg/2 mL (100 mg/mL). Each mL of solution contains 100 mg of lecanemab-irmb and arginine hydrochloride (42.13 mg), histidine (0.18 mg), histidine hydrochloride monohydrate (4.99 mg), polysorbate 80 (0.50 mg), and Water for Injection at an approximate pH of 5.0. LEQEMBI IQLIK Injection for Subcutaneous Use LEQEMBI IQLIK (lecanemab-irmb) injection is a sterile, preservative-free, clear to opalescent and colorless to pale yellow solution for subcutaneous use. LEQEMBI IQLIK is supplied in a single-dose prefilled autoinjector available in the concentration of 360 mg/1.8 mL with a 29-gauge fixed ½-inch needle. Each LEQEMBI IQLIK autoinjector contains 360 mg/1.8 mL lecanemab-irmb formulated in: arginine hydrochloride (75.83 mg), histidine (0.25 mg), histidine hydrochloride monohydrate (9.09 mg), polysorbate 80 (0.90 mg), and Water for Injection, USP.

Hoạt chất

Thành phần	Hàm lượng
Lecanemab	-
Lecanemab-Irmb	-

Chỉ định & Cách dùng

1 INDICATIONS AND USAGE 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. LEQEMBI is an amyloid beta-directed antibody 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. ( 1 )

Cơ chế hoạt động

12.1 Mechanism of Action Lecanemab-irmb is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. The accumulation of amyloid beta plaques in the brain is a defining pathophysiological feature of Alzheimer’s disease. LEQEMBI reduces amyloid beta plaques, as evaluated in Study 1 and Study 2 [see Clinical Studies ( 14 )] .

Liều dùng & Cách dùng

2 DOSAGE AND ADMINISTRATION Confirm the presence of amyloid beta pathology prior to initiating treatment. ( 2.1 ) Obtain a recent baseline brain MRI prior to initiating treatment. ( 2.4 , 5.1 ) Obtain an MRI within approximately one week prior to the 3 rd , 5 th , 7 th , and 14 th infusions. If radiographically observed ARIA occurs, treatment recommendations are based on type, severity, and presence of symptoms. ( 2.4 , 5.1 ) Recommended starting dosage: 10 mg/kg once every 2 weeks administered after dilution as an intravenous infusion over approximately one hour. ( 2.2 ) After 18 months, continue treatment once every 2 weeks or transition to an intravenous or subcutaneous maintenance dosage. ( 2.2 ) Recommended maintenance dosage: Intravenous infusion: 10 mg/kg once every 4 weeks ( 2.2 , 2.5 ) Subcutaneous injection: 360 mg administered once a week using the LEQEMBI IQLIK autoinjector ( 2.2 , 2.6 ). See Full Prescribing Information for preparation and administration instructions. ( 2.5 , 2.6 ) 2.1 Patient Selection Confirm the presence of amyloid beta pathology prior to initiating treatment [see Clinical Pharmacology ( 12.1 )] . 2.2 Recommended Dosage Initiate LEQEMBI as an intravenous infusion using the starting dosage (see Table 1). After 18 months, the starting dosage may be continued or a transition to maintenance dosage regimen may be considered, which can be administered by either intravenous infusion or subcutaneous injection (see Table 1). If transitioning from starting dosage to a maintenance dosage regimen, administer the first maintenance dose two weeks after the last starting dose. Table 1: Starting and Maintenance Dosage Regimens Route of Administration Dose Frequency Infusion Rate (if Intravenous) Starting Dosage Intravenous Only (LEQEMBI) 10 mg/kg Once every 2 weeks Over approximately one hour Maintenance Dosage Intravenous (LEQEMBI) 10 mg/kg Once every 4 weeks Over approximately one hour Subcutaneous (LEQEMBI IQLIK) 360 mg Once every week ------------------------ For intravenous infusion, use LEQEMBI vials. LEQEMBI vials must be diluted before administration [see Dosage and Administration ( 2.5 )]. For subcutaneous administration, use LEQEMBI IQLIK [see Dosage and Administration ( 2.6 )]. 2.3 Switching Between Maintenance Dosage Regimens During maintenance dosage regimen, patients may switch the route of administration (intravenous LEQEMBI or subcutaneous LEQEMBI IQLIK). This transition should be initiated at 1 week following the last maintenance dose of either the intravenous or subcutaneous dosing regimen. Thereafter, follow the dosing schedule for the newly assigned maintenance dosage regimen. 2.4 Monitoring and Dosing Interruption for Amyloid Related Imaging Abnormalities LEQEMBI can cause amyloid related imaging abnormalities -edema (ARIA-E) and -hemosiderin deposition (ARIA-H) [ see Warnings and Precautions ( 5.1 )] . Monitoring for ARIA Obtain a recent baseline brain magnetic resonance imaging (MRI) prior to initiating treatment with LEQEMBI. Obtain an MRI prior to the 3 rd , 5 th , 7 th , and 14 th infusions. In general, the MRI should be performed within approximately one week before the scheduled infusion of LEQEMBI and reviewed prior to proceeding with the infusion. 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 2. Table 2: Dosing Recommendations for Patients with ARIA-E Clinical Symptom Severity 1 ARIA-E Severity on MRI 2 Mild Moderate Severe Asymptomatic May continue dosing Suspend dosing 3 Suspend dosing 3 Mild May continue dosing based on clinical judgment Suspend dosing 3 Moderate or Severe Suspend dosing 3 1 Clinical Symptom Severity Categories: Mild: discomfort noticed, but no disruption of normal daily activity. Moderate: discomfort sufficient to reduce or affect normal daily activity. Severe: incapacitating, with inability to work or to perform normal daily activity. 2 See Table 4 for MRI radiographic severity [Warnings and Precautions ( 5.1 )] . 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. Resumption of dosing should be guided by clinical judgment. ARIA-H The recommendations for dosing interruptions for patients with ARIA-H are provided in Table 3. Table 3: Dosing Recommendations for Patients with ARIA-H Clinical Symptom Severity ARIA-H Severity on MRI 1 Mild Moderate Severe Asymptomatic May continue dosing Suspend dosing 2 Suspend dosing 3 Symptomatic Suspend dosing 2 Suspend dosing 2 1 See Table 4 for MRI radiographic severity [Warnings and Precautions ( 5.1 )] . 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. Use clinical judgment in considering whether to continue treatment after radiographic stabilization and resolution of symptoms or permanently discontinue LEQEMBI. 2.5 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 [see Description ( 11 )] . 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 [see Warnings and Precautions ( 5.3 )]. 2.6 Preparation and Administration of LEQEMBI IQLIK for Subcutaneous Injection 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 [see Instructions for Use ]. Periodically reassess the ability of the patient or caregiver to safely and adequately administer LEQEMBI IQLIK. • 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, upper thigh, and back of the upper arm. • Do not inject into moles, scars, bruises, tattoos or into areas where the skin is red, hard, tender or injured. • Monitor for signs or symptoms of an injection reaction. 2.7 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 maintenance dosing regimen is missed, administer LEQEMBI IQLIK as soon as possible up to 6 days after the missed dose and administer the next dose on the regularly scheduled day. Thereafter, resume the original dosing schedule.

Side Effects Overview

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Amyloid Related Imaging Abnormalities [see Warnings and Precautions ( 5.1 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.2 )] Infusion-Related Reactions [see Warnings and Precautions ( 5.3 )] Most common adverse reactions (at approximately 10% and higher incidence compared to placebo): infusion-related reactions, amyloid related imaging abnormality-microhemorrhages, amyloid related imaging abnormality-edema/effusion, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eisai Inc. at 1-888-274-2378 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. In Studies 1 and 2 in patients with Alzheimer’s disease, 1059 patients received LEQEMBI 10 mg/kg every two weeks by intravenous infusion [see Clinical Studies ( 14 )] . Of these 1059 patients, 50% were female, 79% were White, 15% were Asian, 12% were of Hispanic or Latino ethnicity, and 2% were Black. The mean age at study entry was 72 years (range from 50 to 90 years). In the combined double-blind, placebo-controlled period and long-term extension period of Studies 1 and 2, 1604 patients received LEQEMBI for at least 6 months, 1261 patients for at least 12 months, and 965 patients for 18 months. 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. In Study 1, the most common adverse reaction leading to discontinuation of LEQEMBI was infusion-related reactions that led to discontinuation in 2% (4/161) of patients treated with LEQEMBI, compared to 1% (2/245) of patients on placebo. In Study 2, the most common adverse reaction leading to discontinuation of LEQEMBI was ARIA-H microhemorrhages that led to discontinuation in 2% (15/898) of patients treated with LEQEMBI, compared to <1% (1/897) of patients on placebo. Table 5 shows adverse reactions that were reported in at least 5% of patients treated with LEQEMBI and at least 2% more frequently than in patients on placebo in Study 1. Table 5: 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 1 Adverse Reaction LEQEMBI 10 mg/kg Every Two Weeks N= 161 % Placebo N= 245 % Infusion-related reactions 20 3 Headache 14 10 ARIA-E 10 1 Cough 9 5 Diarrhea 8 5 Table 6 shows adverse reactions that were reported in at least 5% of patients treated with LEQEMBI and at least 2% more frequently than in patients on placebo in Study 2. Table 6: 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 2 Adverse Reaction LEQEMBI 10 mg/kg Every Two Weeks N= 898 % Placebo N= 897 % Infusion-related reactions 26 7 ARIA-H 14 8 ARIA-E 13 2 Headache 11 8 Superficial siderosis of central nervous system 6 3 Rash 1 6 4 Nausea/Vomiting 6 4 1 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 [see Warnings and Precautions ( 5.3 )]; lymphocytes were not measured after the first dose in Study 2. Clinical Trials with Subcutaneous Administration The safety of LEQEMBI IQLIK for maintenance treatment was evaluated in an open-label study, which included 49 patients who received LEQEMBI IQLIK 360 mg by subcutaneous administration once every week. The overall safety profile in these patients was similar to what was observed in patients who received LEQEMBI by intravenous infusion in Study 1 and Study 2. Patients who received LEQEMBI IQLIK experienced localized and systemic injection-related reactions. Localized injection-related reactions included erythema, induration, swelling, heat, pain, pruritis, rash, ecchymosis, and hematoma. Systemic injection-related reactions were observed less frequently, with symptoms of headache, fever, and fatigue. Injection-related reactions in patients receiving LEQEMBI IQLIK were mild or moderate in severity.

Cảnh báo & Thận trọng

5 WARNINGS AND PRECAUTIONS Amyloid Related Imaging Abnormalities (ARIA): Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. Risk of ARIA, including symptomatic ARIA, was increased in apolipoprotein E ε4 homozygotes compared to heterozygotes and noncarriers. The risk of ARIA-E and ARIA-H is increased in patients with pretreatment microhemorrhages and/or superficial siderosis. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI scanning if indicated. ( 2.4 , 5.1 ) Infusion-Related Reactions: 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. ( 5.3 ) 5.1 Amyloid Related Imaging Abnormalities Monoclonal antibodies directed against aggregated forms of beta amyloid, including LEQEMBI, can cause amyloid related imaging abnormalities (ARIA), characterized as ARIA with edema (ARIA-E), which can be observed on MRI as brain edema or sulcal effusions, and ARIA with hemosiderin deposition (ARIA-H), which includes microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with Alzheimer’s disease, particularly in patients with MRI findings suggestive of cerebral amyloid angiopathy, such as pretreatment microhemorrhage or superficial siderosis. ARIA-H associated with monoclonal antibodies directed against aggregated forms of beta amyloid generally occurs in association with an occurrence of ARIA-E. ARIA-H of any cause and ARIA-E can occur together. ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, can occur. ARIA can be fatal. When present, reported symptoms associated with ARIA may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve over time. In addition to ARIA, intracerebral hemorrhages greater than 1 cm in diameter have occurred in patients treated with LEQEMBI. Consider the benefit of LEQEMBI for the treatment of Alzheimer’s disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment with LEQEMBI. Incidence of ARIA Symptomatic ARIA occurred in 3% (29/898) of patients treated with LEQEMBI in Study 2 [see Clinical Studies ( 14 )]. Serious symptoms associated with ARIA were reported in 0.7% (6/898) of patients treated with LEQEMBI. Clinical symptoms associated with ARIA resolved in 79% (23/29) of patients during the period of observation. Similar findings were observed in Study 1. Including asymptomatic radiographic events, ARIA was observed in 21% (191/898) of patients treated with LEQEMBI, compared to 9% (84/897) of patients on placebo in Study 2. In Study 2, ARIA-E was observed in 13% (113/898) of patients treated with LEQEMBI, compared to 2% (15/897) of patients on placebo. ARIA-H was observed in 17% (152/898) of patients treated with LEQEMBI, compared to 9% (80/897) of patients on placebo. There was no increase in isolated ARIA-H (i.e., ARIA-H in patients who did not also experience ARIA-E) for LEQEMBI compared to placebo. Incidence of Intracerebral Hemorrhage Intracerebral hemorrhage greater than 1 cm in diameter was reported in 0.7% (6/898) of patients in Study 2 after treatment with LEQEMBI, compared to 0.1% (1/897) on placebo. Fatal events of intracerebral hemorrhage in patients taking LEQEMBI have been observed. Risk Factors for ARIA and Intracerebral Hemorrhage ApoE ε4 Carrier Status The risk of ARIA, including symptomatic and serious ARIA, is increased in apolipoprotein E ε4 (ApoE ε4) homozygotes. Approximately 15% of Alzheimer’s disease patients are ApoE ε4 homozygotes. In Study 2, 16% (141/898) of patients in the LEQEMBI arm were ApoE ε4 homozygotes, 53% (479/898) were heterozygotes, and 31% (278/898) were noncarriers. The incidence of ARIA was higher in ApoE ε4 homozygotes (45% on LEQEMBI vs. 22% on placebo) than in heterozygotes (19% on LEQEMBI vs 9% on placebo) and noncarriers (13% on LEQEMBI vs 4% on placebo). Among patients treated with LEQEMBI, symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes compared to 2% of heterozygotes and 1% noncarriers. Serious events of ARIA occurred in 3% of ApoE ε4 homozygotes, and approximately 1% of heterozygotes and noncarriers. The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers [see Dosage and Administration ( 2.4 )]. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. Prescribers should inform patients that if genotype testing is not performed they can still be treated with LEQEMBI; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA. Radiographic Findings of Cerebral Amyloid Angiopathy (CAA) Neuroimaging findings that may indicate CAA include evidence of prior intracerebral hemorrhage, cerebral microhemorrhage, and cortical superficial siderosis. CAA has an increased risk for intracerebral hemorrhage. The presence of an ApoE ε4 allele is also associated with cerebral amyloid angiopathy. The baseline presence of at least 2 microhemorrhages or the presence of at least 1 area of superficial siderosis on MRI, which may be suggestive of CAA, have been identified as risk factors for ARIA. Patients were excluded from enrollment in Study 2 for the presence of more than 4 microhemorrhages and additional findings suggestive of cerebral amyloid angiopathy (prior cerebral hemorrhage greater than 1 cm in greatest diameter, superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation) that could potentially increase the risk of intracerebral hemorrhage. Concomitant Antithrombotic or Thrombolytic Medication In Study 2, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed if the patient was on a stable dose. The majority of exposures to antithrombotic medications were to aspirin. Antithrombotic medications did not increase the risk of ARIA with LEQEMBI. The incidence of intracerebral hemorrhage was 0.9% (3/328 patients) in patients taking LEQEMBI with a concomitant antithrombotic medication at the time of the event, compared to 0.6% (3/545 patients) in those who did not receive an antithrombotic. Patients taking LEQEMBI with an anticoagulant alone or combined with an antiplatelet medication or aspirin had an incidence of intracerebral hemorrhage of 2.5% (2/79 patients), compared to none in patients who received placebo. Fatal cerebral hemorrhage has occurred in a patient taking an anti-amyloid monoclonal antibody in the setting of focal neurologic symptoms of ARIA and the use of a thrombolytic agent. Additional caution should be exercised when considering the administration of antithrombotics or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, treating clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy in a patient being treated with LEQEMBI. Caution should be exercised when considering the use of LEQEMBI in patients with factors that indicate an increased risk for intracerebral hemorrhage and in particular for patients who need to be on anticoagulant therapy, or patients with findings on MRI that are suggestive of cerebral amyloid angiopathy. Radiographic Severity The radiographic severity of ARIA associated with LEQEMBI was classified by the criteria shown in Table 4. Table 4: ARIA MRI Classification Criteria ARIA Type Radiographic Severity Mild Moderate Severe ARIA-E FLAIR hyperintensity confined to sulcus and/or cortex/subcortex white matter in one location <5 cm FLAIR hyperintensity 5 to 10 cm in single greatest dimension, or more than 1 site of involvement, each measuring <10 cm FLAIR hyperintensity >10 cm with associated gyral swelling and sulcal effacement. One or more separate/ independent sites of involvement may be noted. ARIA-H microhemorrhage ≤ 4 new incident microhemorrhages 5 to 9 new incident microhemorrhages 10 or more new incident microhemorrhages ARIA-H superficial siderosis 1 focal area of superficial siderosis 2 focal areas of superficial siderosis > 2 areas of superficial siderosis In Study 2, the majority of ARIA-E radiographic events occurred early in treatment (within the first 7 doses), although ARIA can occur at any time and patients can have more than 1 episode. The maximum radiographic severity of ARIA-E in patients treated with LEQEMBI was mild in 4% (37/898) of patients, moderate in 7% (66/898) of patients, and severe in 1% (9/898) of patients. Resolution on MRI occurred in 52% of ARIA-E patients by 12 weeks, 81% by 17 weeks, and 100% overall after detection. The maximum radiographic severity of ARIA-H microhemorrhage in patients treated with LEQEMBI was mild in 9% (79/898), moderate in 2% (19/898), and severe in 3% (28/898) of patients; superficial siderosis was mild in 4% (38/898), moderate in 1% (8/898), and severe in 0.4% (4/898). Among patients treated with LEQEMBI, the rate of severe radiographic ARIA-E was highest in ApoE ε4 homozygotes 5% (7/141), compared to heterozygotes 0.4% (2/479) or noncarriers 0% (0/278). Among patients treated with LEQEMBI, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes 13.5% (19/141), compared to heterozygotes 2.1% (10/479) or noncarriers 1.1% (3/278). Monitoring and Dose Management Guidelines Recommendations for dosing in patients with ARIA-E depend on clinical symptoms and radiographic severity [see Dosage and Administration ( 2.4 )]. Recommendations for dosing in patients with ARIA-H depend on the type of ARIA-H and radiographic severity [see Dosage and Administration ( 2.4 )] . Use clinical judgment in considering whether to continue dosing in patients with recurrent ARIA-E. Baseline brain MRI and periodic monitoring with MRI are recommended [see Dosage and Administration ( 2.4 )] . Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment. There is no experience in patients who continued dosing through symptomatic ARIA-E, or through asymptomatic but radiographically severe ARIA-E. There is limited experience in patients who continued dosing through asymptomatic but radiographically mild to moderate ARIA-E. There are limited data in dosing patients who experienced recurrent ARIA-E. While experience is limited in these situations, dose management guidelines are provided [see Dosage and Administration ( 2.4 )]. Providers should encourage patients to participate in real world data collection (e.g., registries) to help further the understanding of Alzheimer’s disease and the impact of Alzheimer’s disease treatments. Providers and patients can contact Eisai at 888-274-2378 for a list of currently enrolling programs. 5.2 Hypersensitivity Reactions Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred in patients who were treated with LEQEMBI. If LEQEMBI is being administered intravenously, promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction, and initiate appropriate therapy. LEQEMBI is contraindicated in patients with a history of serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI or LEQEMBI IQLIK. 5.3 Infusion-Related Reactions In Study 2, infusion-related reactions were observed in 26% (237/898) of patients treated with LEQEMBI, compared to 7% (66/897) of patients on placebo; and the majority (75%, 178/237) occurred with the first infusion. Infusion-related reactions were mostly mild (69%) or moderate (28%) in severity. Infusion-related reactions resulted in discontinuations in 1% (12/898) of patients treated with LEQEMBI. Symptoms of infusion-related reactions include fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation. After the first infusion in Study 1, 38% of patients treated with LEQEMBI had transient decreased lymphocyte counts to less than 0.9 x10 9 /L, compared to 2% in patients on placebo, and 22% of patients treated with LEQEMBI had transient increased neutrophil counts to greater than 7.9 x10 9 /L, compared to 1% of patients on placebo. Lymphocyte and neutrophil counts were not obtained after the first infusion in Study 2. Infusion-related reactions can occur during the infusion or after completion of the infusion. In the event of an infusion-related reaction during the infusion, the infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Consider prophylactic treatment with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids prior to future infusions.

Chống chỉ định

4 CONTRAINDICATIONS LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI or LEQEMBI IQLIK. Reactions have included angioedema and anaphylaxis [see Warnings and Precautions ( 5.2 )]. LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI or LEQEMBI IQLIK. ( 4 )

Dược động học

12.3 Pharmacokinetics Steady-state concentrations of lecanemab-irmb were reached after 6 weeks of 10 mg/kg administered every 2 weeks and systemic accumulation was 1.4-fold. The peak concentration (C max ) and area under the plasma concentration versus time curve (AUC) of lecanemab-irmb increased dose proportionally in the dose range of 0.3 to 15 mg/kg following single dose. The estimated mean steady-state concentrations of lecanemab-irmb following 10 mg/kg biweekly intravenous infusion, 10 mg/kg monthly intravenous infusion and 360 mg weekly subcutaneous administration by autoinjector are provided in Table 8. Using population pharmacokinetic modeling and simulation, the intravenous (10 mg/kg once every 4 weeks) and subcutaneous (360 mg once weekly) maintenance dosing regimens of lecanemab-irmb were predicted to have similar pharmacokinetic exposure. Table 8: Estimated Systemic Exposure of Lecanemab-irmb at Steady State in Patients with Alzheimer’s Disease* C av g ,ss (mcg/mL) Mean (CV%) Intravenous infusion 10 mg/kg every two weeks 156 (37.7) Intravenous infusion 10 mg/kg every four weeks 78.1 (37.7) Subcutaneous injection 360 mg weekly 83.1 (58.8) *Based on simulations in 1000 virtual patients Absorption The bioavailability of lecanemab-irmb following subcutaneous administration of 360 mg by autoinjector relative to a 10 mg/kg intravenous infusion in patients was approximately 53% and was not affected by the injection site (abdomen, upper thigh, or back of the upper arm). Distribution The mean value (95% CI) for central volume of distribution at steady state is 3.24 (3.18-3.30) L. Elimination Lecanemab-irmb is degraded by proteolytic enzymes in the same manner as endogenous IgGs. The clearance of lecanemab-irmb (95% CI) is 0.370 (0.353-0.384) L/day. The terminal half-life is 5 to 7 days. Specific Populations Sex, body weight, and albumin were found to impact exposure to lecanemab-irmb. However, none of these covariates were found to be clinically significant. Patients with Renal or Hepatic Impairment No clinical studies were conducted to evaluate the pharmacokinetics of lecanemab-irmb in patients with renal or hepatic impairment. Lecanemab-irmb is degraded by proteolytic enzymes and is not expected to undergo renal elimination or metabolism by hepatic enzymes.

Frequently Asked Questions

1 INDICATIONS AND USAGE 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. LEQEMBI is an amyloid beta-directed antibody 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 …

2 DOSAGE AND ADMINISTRATION Confirm the presence of amyloid beta pathology prior to initiating treatment. ( 2.1 ) Obtain a recent baseline brain MRI prior to initiating treatment. ( 2.4 , 5.1 ) Obtain an MRI within approximately one week prior to the 3 rd , 5 th , 7 th , and 14 th infusions. If radiographically observed ARIA occurs, treatment recommendations are based on type, severity, and presence of symptoms. ( 2.4 , 5.1 ) Recommended starting dosage: …

5 WARNINGS AND PRECAUTIONS Amyloid Related Imaging Abnormalities (ARIA): Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. Risk of ARIA, including symptomatic ARIA, was increased in apolipoprotein E ε4 homozygotes compared to heterozygotes and noncarriers. The risk of ARIA-E and ARIA-H is increased in patients with pretreatment microhemorrhages and/or superficial siderosis. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI scanning if indicated. ( 2.4 , …

4 CONTRAINDICATIONS LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI or LEQEMBI IQLIK. Reactions have included angioedema and anaphylaxis [see Warnings and Precautions ( 5.2 )]. LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI or LEQEMBI IQLIK. ( 4 )

Lecanemab is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

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References & Data Sources

• DailyMed — Lecanemab drug label (National Library of Medicine)
• openFDA — Lecanemab label data (U.S. Food & Drug Administration)
• RxNorm — RXCUI 2626147 (NLM Normalized Drug Names)
• NDC Directory — Lecanemab (FDA National Drug Code)

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Nguồn dữ liệu: DailyMed (NLM), openFDA, MFDS