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 )

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.