BRIEF SUMMARY-

LECANEMAB-imb-(Jan 2023)-

Indication-  To treat Alzheimer's disease

Comp-  Injection: • 500 mg/5 mL (100 mg/mL) solution in a single-dose vial                      • 200 mg/2 mL (100 mg/mL) solution in a single-dose vial -                                               • recommended dosage is 10 mg/kg that must be diluted then administered as an intravenous infusion over approximately one hour, once every two weeks.

 ADR- Most common adverse reactions ): infusion-related reactions, headache, and ARIA-edema.

CI-  None.

 WARNINGS-  • Amyloid Related Imaging Abnormalities (ARIA): Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment 

Pat inform- Inform patients that most people with swelling in areas of the brain do not experience symptoms, however, some people may experience symptoms such as headache, confusion, dizziness, vision changes, nausea, aphasia, weakness, or seizure.

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U.S.  APPROVED DRUGS DURING 2023                                        

Serial No 1

Name-        LEGEMBI

Acive  Ingredient -  Lecanemab-irmb

Pharmacological clssificiation-        To treat Alzheimer's disease                                                                                                                                                                                    Date of Approval-         1/6/2023

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                   LEQEMBI™ safely and effectively. See full prescribing information for LEQEMBI™. LEQEMBI™ (lecanemab-irmb) injection, for intravenous use

Initial U.S. Approval: 2023

 INDICATIONS AND USAGE-

 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.

There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.

This indication is approved under accelerated approval based on reduction in amyloid beta plaques observed in patients treated with LEQEMBI. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.

CONTRAINDICATIONS-

 None.

 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 e4 homozygotes compared to heterozygotes and noncarriers. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI scanning if indicated.

 • 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. 

 ADVERSE REACTIONS-

 Most common adverse reactions (at approximately 10% and higher incidence compared to placebo): infusion-related reactions, headache, and ARIA-edema.

 DOSAGE FORMS AND STRENGTHS -

 Injection: • 500 mg/5 mL (100 mg/mL) solution in a single-dose vial (3) • 200 mg/2 mL (100 mg/mL) solution in a single-dose vial 

 CONTRAINDICATIONS-

 None.

 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 e4 homozygotes compared to heterozygotes and noncarriers. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI scanning if indicated.

 • 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. 

DOSAGE AND ADMINISTRATION-

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

 • The recommended dosage is 10 mg/kg that must be diluted then administered as an intravenous infusion over approximately one hour, once every two weeks.

 • Obtain a recent (within one year) brain MRI prior to initiating treatment to evaluate for pre-existing Amyloid Related Imaging Abnormalities (ARIA).

 • Obtain an MRI prior to the 5th, 7th, and 14th infusions. If radiographically observed ARIA occurs, treatment recommendations are based on type, severity, and presence of symptoms.

 • Dilution in 250 mL of 0.9% Sodium Chloride Injection, USP, is required prior to administration.

 • Administer as an intravenous infusion over approximately one hour via a terminal low-protein binding 0.2 micron in-line filter. 

 DOSAGE FORMS AND STRENGTHS -

 Injection: • 500 mg/5 mL (100 mg/mL) solution in a single-dose vial                                   • 200 mg/2 mL (100 mg/mL) solution in a single-dose vial 

PATIENT COUNSELING INFORMATION -

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide).

Amyloid Related Imaging Abnormalities-                                                                   Inform patients that LEQEMBI may cause Amyloid Related Imaging Abnormalities or “ARIA”. ARIA most commonly presents as a temporary swelling in areas of the brain that usually resolves over time. Some people may also have small spots of bleeding in or on the surface of the brain.

Inform patients that most people with swelling in areas of the brain do not experience symptoms, however, some people may experience symptoms such as headache, confusion, dizziness, vision changes, nausea, aphasia, weakness, or seizure.

Instruct patients to notify their healthcare provider if these symptoms occur.

Inform patients that events of intracerebral hemorrhage greater than 1 cm in diameter have been reported infrequently in patients taking LEQEMBI, and that the use of antithrombotic or thrombolytic medications while taking LEQEMBI may increase the risk of bleeding in the brain. Notify patients that their healthcare provider will perform MRI scans to monitor for ARIA .

Inform patients that although ARIA can occur in any patient treated with LEQEMBI, there is an increased risk in patients who are ApoE e4 homozygotes, and that there is a test available to determine ApoE e4 genotype.

Patient Registry-                                                                                                         Advise patients that the Alzheimer’s Network for Treatment and Diagnostics (ALZ-NET) is a voluntary provider-enrolled patient registry that collects information on treatments for Alzheimer’s disease, including LEQEMBI.

Encourage patients to participate in the ALZ-NET registry.

Infusion-Related Reactions-                                                                                           Advise patients of the potential risk of infusion-related reactions, which can include flu-like symptoms, nausea, vomiting, and changes in blood pressure, the majority of which occur with the first infusion.

Manufactured by: Eisai Inc. Nutley, NJ 07110 U.S. License No. 1862 LEQEMBITM is a trademark of Eisai R&D Management Co., Ltd. © XXXX Eisai Inc. and Biogen

CLINICAL PHARMACOLOGY

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.

2. Pharmacodynamics-                                                                                             Effect of LEQEMBI on Amyloid Beta Pathology LEQEMBI reduced amyloid beta plaque in a dose- and time-dependent manner in Study , compared with placebo.

The effect of LEQEMBI on amyloid beta plaque levels in the brain was evaluated using PET imaging ( 18F-florbetapir tracer).

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 (Cmax) 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.

 Distribution-                                                                                                                  The mean value (95% CI) for central volume of distribution at steady-state is 3.22 (3.15-3.28) L.

Elimination-                                                                                                      Lecanemab-irmb is degraded by proteolytic enzymes in the same manner as endogenous IgGs. The clearance of lecanemab-irmb (95% CI) is 0.434 (0.420-0.451) 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.

USE IN SPECIFIC POPULATIONS

1. 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 U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

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

2. Lactation Risk Summary-                                                                                       There are no data on the presence of lecanemab-irmb in human milk, the effects on the breastfed infant, or the effects of the drug on milk production.

Published data from other monoclonal antibodies generally indicate low passage of monoclonal antibodies into human milk and limited systemic exposure in the breastfed infant. The effects of this limited exposure are unknown.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LEQEMBI and any potential adverse effects on the breastfed infant from LEQEMBI or from the underlying maternal condition.

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

4.Geriatric Use-                                                                                                                In Study 1, the age of patients exposed to LEQEMBI 10 mg/kg every two weeks ranged from 51 to 88 years, with a mean age of 73 years; 62% were 65 to 80 years, and 21% were 80 years and older.

Age-related findings about clinical efficacy and safety are limited by the small numbers of patients less than 65 years of age and 80 years of age and older in clinical studies of LEQEMBI