EXDENSUR Solution for injection Ref.[116117] Active ingredients: Depemokimab

5.1 Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, can occur following administration of EXDENSUR. If a hypersensitivity reaction occurs, discontinue EXDENSUR and initiate appropriate therapy.

5.2 Acute Asthma Symptoms or Deteriorating Disease

EXDENSUR should not be used to treat acute asthma symptoms or acute exacerbations. Do not use EXDENSUR to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with EXDENSUR.

5.3 Risk Associated with Abrupt Reduction of Corticosteroid Dosage

Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy. Do not abruptly discontinue systemic or inhaled corticosteroids upon initiation of EXDENSUR therapy. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the supervision of a healthcare provider.

5.4 Parasitic (Helminth) Infection

Eosinophils may be involved in the immunological response to some helminth infections. Patients with pre-existing helminth infections were excluded from participation in the clinical trials. It is unknown if EXDENSUR will influence a patient's response against parasitic infections. Patients with pre-existing helminth infections should be treated for their infection prior to initiation of EXDENSUR therapy. If patients become infected while receiving treatment with EXDENSUR and do not respond to anti-helminth treatment, discontinue treatment with EXDENSUR until the infection resolves.

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Hypersensitivity Reactions [see Warnings and Precautions (5.1)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of EXDENSUR was based on a pooled safety population from 2 replicate, randomized, double-blind, parallel-group, placebo-controlled, multicenter clinical trials (SWIFT-1 and SWIFT-2) of 52 weeks duration. The 2 trials included 762 adult and pediatric patients 12 years of age and older with asthma, who received either EXDENSUR 100 mg or placebo administered subcutaneously once every 6 months in addition to their existing background medications for asthma [see Clinical Studies (14)]. A total of 475 patients received 2 doses of EXDENSUR 100 mg in these trials.

Adverse reactions with EXDENSUR with incidence of ≥4% are shown in Table 1.

Table 1. Adverse Reactions with EXDENSUR with an Incidence ≥4% and More Common than Placebo in Patients with Asthma:

Specific Adverse Reactions

Injection Site Reactions

In the pooled safety population (SWIFT-1 and SWIFT-2), in which EXDENSUR was administered by a healthcare provider, injection site reactions (e.g., erythema, swelling, and itching) occurred in 7 (1%) and 2 (<1%) patients receiving EXDENSUR and placebo, respectively.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies (ADA) in the studies described below with the incidence of ADA in other studies, including those of EXDENSUR or of other depemokimab products.

In adults and pediatric patients aged 12 years and older with asthma, the incidence of ADA to depemokimab in patients treated with EXDENSUR 100 mg once every 6 months in SWIFT-1, SWIFT-2, and an open-label extension was 10% (66/691). Among ADA-positive patients, 6% (4/66) developed neutralizing antibodies.

There was no identified clinically significant effect of ADA on the pharmacokinetics, pharmacodynamics, safety, or efficacy of EXDENSUR.

Risk Summary

Available data from clinical trials with EXDENSUR use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with asthma in pregnancy (see Clinical Considerations).

Transport of endogenous IgG antibodies and monoclonal antibodies, such as depemokimab-ulaa, across the placenta increases as pregnancy progresses and peaks during the third trimester. The impact of the YTE modification on placental transfer is uncertain [see Clinical Pharmacology (12.1)]; however, the presence of the YTE modification may lead to prolonged and increased exposure of the infant exposed in utero, and the potential of clinical impact is unknown and should be considered. No treatment-related effects on embryofetal or postnatal development have been shown in animal studies targeting IL-5 signaling pathways (see Data).

The background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.

Pregnant women exposed to EXDENSUR, or their healthcare providers, should report EXDENSUR exposure by calling 1-888-825-5249.

Clinical Considerations

Disease-Associated Maternal and/or Embryofetal Risk

In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother, and prematurity, low birth weight, and small for gestational age in the neonate. The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control.

Data

Animal Data

Reproductive toxicology studies have not been conducted with depemokimab-ulaa. In animal studies targeting the IL-5 signaling pathway with a related biologic product without the YTE modification, there were no developmental effects observed [see Nonclinical Toxicology (13)]. Embryofetal development of IL-5 deficient mice has been reported to be generally unaffected relative to wild-type mice.

Risk Summary

There are no data on the presence of depemokimab-ulaa in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. However, depemokimab-ulaa is a humanized monoclonal antibody (immunoglobulin G1 [IgG1] kappa), and maternal IgG is present in human milk in small amounts. The effects of local gastrointestinal exposure and the extent of systemic exposure in the breastfed infant to EXDENSUR are unknown.

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

Asthma

The safety and effectiveness of EXDENSUR for add-on maintenance treatment of severe asthma characterized by an eosinophilic phenotype have been established in pediatric patients aged 12 years and older.

Use of EXDENSUR for this indication is supported by evidence from adequate and well-controlled trials (SWIFT-1 and SWIFT-2) in adults and pediatric patients aged 12 years and older, and pharmacokinetic data in pediatric patients aged 12 years and older. A total of 30 pediatric patients aged 12 to 17 years with asthma were enrolled in the SWIFT-1 and SWIFT-2 trials, of whom 15 received EXDENSUR 100 mg. Pharmacokinetic and pharmacodynamic data have demonstrated no clinically significant differences in systemic exposure of depemokimab-ulaa and reduction in blood eosinophil counts in pediatric patients aged 12 years and older compared to that observed in adults following administration of the recommended dosage of EXDENSUR. The safety of EXDENSUR in pediatric patients aged 12 years and older was generally similar to that of the adult population in SWIFT-1 and SWIFT-2 [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14)].

The safety and effectiveness of EXDENSUR have not been established in pediatric patients younger than 12 years of age.

Of the 501 patients with asthma treated with EXDENSUR, 133 (27%) were 65 years of age and older and 22 (4%) were 75 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients.