Leqembi Adverse Reactions

Experience in clinical studies: The safety of LEQEMBI has been evaluated in 2090 patients who received at least one dose of LEQEMBI. In Studies 1 and 2 in patients with Alzheimer's disease, 1059 patients received LEQEMBI 10 mg/kg every two weeks (see Pharmacology: Pharmacodynamics under Actions). 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 microhaemorrhages that led to discontinuation in 2% (15/898) of patients treated with LEQEMBI compared to <1% (1/897) of patients on placebo.
Table 7 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. (See Table 7.)

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Table 8 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. (See Table 8.)

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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 were reported in 4% of patients treated with LEQEMBI after the first dose, compared to less than 1% of patients on placebo (see Precautions); lymphocytes were not measured after the first dose in Study 2.
Description of selected adverse reactions: The following clinically significant adverse reactions are described elsewhere in the labeling: Amyloid related imaging abnormalities (see Precautions), Hypersensitivity reactions (see Precautions), Infusion-related reactions (see Precautions).
ApoE ε4 Carrier Status and Risk of ARIA (see Precautions): In Study 2, 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). Serious events of ARIA occurred in 3% of ApoE ε4 homozygotes, and approximately 1% of heterozygotes and noncarriers.
ARIA-E: Among patients treated with LEQEMBI, the rate of ARIA-E was 33% in ApoE ε4 homozygotes, 11% in heterozygotes and 5% in noncarriers. Symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes compared with 2% of heterozygotes and 1% noncarriers. Of the genotypes, ApoE ε4 homozygotes had a higher incidence of serious ARIA-E (2.1%) compared to noncarriers (0.7%) and heterozygotes (0.4%).
Among the patients who experienced an event of ARIA-E and continued on LEQEMBI with or without dose interruption, the rates of recurrence were 54% in homozygotes compared with 15% in heterozygotes and 9% in noncarriers.
ApoE ε4 carrier status had no impact on the timing to onset of ARIA-E. Timing and rate of ARIA-E resolution were also similar across ApoE ε4 genotypes, with most resolving within 4 months.
Symptoms of ARIA-E also did not differ across genotypes.
ARIA-H: Among patients treated with LEQEMBI, the rate of ARIA-H (with or without concurrent ARIA-E) was 38% in ApoE ε4 homozygotes, 14% in heterozygotes and 12% in noncarriers. Symptomatic ARIA-H occurred in 4% of ApoE ε4 homozygotes compared with 1% of heterozygotes and 1% noncarriers. Only two serious ARIA-H events were reported from one ApoE ε4 noncarrier and one homozygote in Study 2.
Among the patients who experienced an event of ARIA-H (with or without concurrent ARIA-E) and continued on LEQEMBI with or without dose interruption, the rates of recurrence were 62% in homozygotes compared with 42% in heterozygotes and 22% in noncarriers.
ApoE ε4 carrier status had no impact on the timing to onset of ARIA-H. Isolated ARIA-H events in placebo group and treatment group were distributed over the course of treatment and occurred at a similar rate.
Symptoms of overall ARIA-H were similar across genotypes.
ARIA-H does not typically resolve radiographically, as haemosiderin deposition is typically not reabsorbed.