Donanemab

Patients who are apolipoprotein E ε4 (ApoE ε4) homozygotes (approximately 15% of Alzheimer’s disease patients) treated with this class of medications, including donanemab, have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers. 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 donanemab; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA.

There are no adequate data on donanemab 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 donanemab.

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 donanemab 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 donanemab and any potential adverse effects on the breastfed infant from donanemab 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 donanemab on male or female fertility.

• 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 donanemab has been evaluated in 2885 patients with Alzheimer’s disease who received at least one dose of donanemab intravenously. In the clinical studies of donanemab, 1912 patients with Alzheimer’s disease received donanemab once monthly for at least 6 months, 1057 patients for at least 12 months, and 432 patients for at least 18 months, at the recommended dosing schedule.

In Study 1 (NCT04437511), a total of 853 patients with Alzheimer’s disease received at least one dose of donanemab.

Thirteen percent of patients treated with donanemab compared to 4% of patients on placebo stopped study treatment because of an adverse reaction. The most common adverse reaction leading to discontinuation of donanemab was infusion-related reaction (4% of patients treated with donanemab compared to no patient on placebo).

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

Adverse reactions reported in at least 5% of patients treated with donanemab and at least 2% higher than placebo in Study 1:

^a As assessed by MRI. A participant could have both microhemorrhage and superficial siderosis.

Less Common Adverse Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, occurred in 3% of patients treated with donanemab compared to 0.7% of patients on placebo.

Intestinal obstruction and intestinal perforation

Three patients (0.4%) treated with donanemab had serious adverse reactions of intestinal obstruction compared to no patients on placebo. Two patients (0.2%) treated with donanemab had serious adverse reactions of intestinal perforation compared to one patient (0.1%) on placebo.

Immunogenicity: Anti-Drug Antibody-associated adverse reactions

In Study 1, approximately 10% of donanemab-treated patients who developed anti-drug antibodies (ADA) reported infusionrelated reactions compared to 2% of patients who did not develop ADA.