Lecanemab

There are no adequate data on lecanemab 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 lecanemab.

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.

There are no data on the presence of lecanemab 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 lecanemab and any potential adverse effects on the breastfed infant from lecanemab or from the underlying maternal condition.

Carcinogenesis

Carcinogenicity studies have not been conducted.

Mutagenesis

Genotoxicity studies have not been conducted.

Impairment of Fertility

No studies in animals have been conducted to assess the effects of lecanemab-irmb on male or female fertility. No adverse effects on male or female reproductive organs were observed in a 39-week intravenous toxicity study in monkeys administered lecanemab-irmb weekly at doses up to 100 mg/kg. The highest dose tested was associated with plasma exposures (C_ave) approximately 27 times that in humans at the recommended human dose (10 mg/kg every two weeks).

• Amyloid Related Imaging Abnormalities.
• Hypersensitivity Reactions.
• Infusion-Related Reactions.

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.

The safety of lecanemab has been evaluated in 2090 patients who received at least one dose of lecanemab. In Studies 1 and 2 in patients with Alzheimer’s disease, 1059 patients received lecanemab 10 mg/kg every two weeks. 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 lecanemab 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 lecanemab, compared to 6% patients on placebo; in Study 2 patients stopped study treatment because of an adverse reaction in 7% of patients treated with lecanemab, compared to 3% patients on placebo. In Study 1, the most common adverse reaction leading to discontinuation of lecanemab was infusion-related reactions that led to discontinuation in 2% (4/161) of patients treated with lecanemab compared to 1% (2/245) of patients on placebo. In Study 2, the most common adverse reaction leading to discontinuation of lecanemab was ARIA-H microhemorrhages that led to discontinuation in 2% (15/898) of patients treated with lecanemab compared to <1% (1/897) of patients on placebo.

Table 1 shows adverse reactions that were reported in at least 5% of patients treated with lecanemab and at least 2% more frequently than in patients on placebo in Study 1.

Table 1. Adverse Reactions Reported in at Least 5% of Patients Treated with Lecanemab 10 mg/kg Every Two Weeks and at least 2% Higher than Placebo in Study 1:

Table 2 shows adverse reactions that were reported in at least 5% of patients treated with lecanemab and at least 2% more frequently than in patients on placebo in Study 2.

Table 2. Adverse Reactions Reported in at Least 5% of Patients Treated with Lecanemab 10 mg/kg Every Two Weeks and at least 2% Higher than Placebo in Study 2:

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 lecanemab compared to 2% in patients on placebo. In Study 1, lymphopenia or decreased lymphocyte count were reported in 4% of patients treated with lecanemab after the first dose, compared to less than 1% of patients on placebo; lymphocytes were not measured after the first dose in Study 2.