MAINTENANCE TREATMENT — An inhaled corticosteroid (ICS) is the most effective maintenance treatment for asthma of any severity. Daily low-dose ICS treatment suppresses airway inflammation and reduces symptoms and exacerbations. Patients who remain symptomatic despite adherence to ICS monotherapy and good inhalation technique should receive maintenance treatment with a combination of an ICS and an inhaled long-acting beta₂-agonist (LABA) plus an as-needed inhaled short-acting beta₂-agonist (SABA), or maintenance and reliever therapy (MART) with an ICS plus formoterol. In patients with asthma that remains uncontrolled despite medium- to high-dose ICS/LABA treatment, addition of an inhaled long-acting muscarinic antagonist (LAMA) can improve lung function.4-6

In patients with moderate to severe eosinophilic asthma, addition of an IL-5-directed agent (mepolizumab, reslizumab, or benralizumab) or the IL-4 and IL-13 inhibitor dupilumab (Dupixent) to maintenance treatment has reduced exacerbations and oral corticosteroid doses. In patients ≥12 years old with severe asthma, addition of the thymic stromal lymphopoietin (TSLP) blocker tezepelumab (Tezspire) has improved lung function and reduced exacerbations. Addition of the anti-IgE monoclonal antibody omalizumab (Xolair) has improved asthma control and decreased exacerbations in patients with moderate to severe allergic asthma. Allergen-specific immunotherapy may be helpful in some patients with allergic asthma.4-6

MECHANISM OF ACTION — Depemokimab is a humanized monoclonal antibody that binds to IL-5, the major cytokine responsible for the growth, differentiation, recruitment, and activation of eosinophils. Inhibition of IL-5 leads to a reduction in eosinophil production and survival and airway inflammation. Depemokimab contains a triple amino acid substitution that prolongs its elimination half-life.

CLINICAL STUDIES — FDA approval of depemokimab was based on the results of two double-blind trials (SWIFT-1 and -2) in 792 patients with severe asthma and a high eosinophil count (≥300 cells/mcL in the previous 12 months or ≥150 cells/mcL at screening) and a history of exacerbations despite treatment with a medium- or high-dose ICS. Patients were randomized to receive depemokimab 100 mg or placebo SC at weeks 0 and 26 in addition to background asthma therapy. The annualized rate of exacerbations at 52 weeks, the primary endpoint, was statistically significantly lower with depemokimab than with placebo in both trials (see Table 2). Treatment with depemokimab did not significantly improve quality of life, a secondary endpoint. The two groups had similar changes from baseline in prebronchodilator forced expiratory volume in 1 second (FEV₁) at 52 weeks (pooled FEV₁ change was 0.20 L with depemokimab vs 0.17 L with placebo). Depemokimab reduced blood eosinophil counts by 83% in SWIFT-1 and by 82% in SWIFT-2.7

In an open-label extension (AGILE; available only as an abstract), 629 patients who completed the SWIFT trials either continued or were switched to depemokimab. After 52 weeks, the annualized exacerbation rate was 0.46 in patients who previously received depemokimab and 0.48 in those who previously received placebo.8

ADVERSE EFFECTS — The most common adverse effects of depemokimab in the SWIFT trials (occurring in ≥4% of patients and more often than with placebo) were upper respiratory tract infection, allergic rhinitis, influenza, arthralgia, and pharyngitis. Injection-site reactions, including erythema, swelling, and itching, have also occurred.

Hypersensitivity reactions, including anaphylaxis, can occur with depemokimab. Delayed hypersensitivity reactions have been reported with anti-IL-5 monoclonal antibodies.

Whether depemokimab can impair the immunological response to helminth infections is unknown. Patients with pre-existing helminth infections should be treated before starting depemokimab.

PREGNANCY AND LACTATION — There are no adequate studies of depemokimab use in pregnant women. Endogenous IgG and monoclonal antibodies such as depemokimab can cross the placenta, particularly during the third trimester.

There are no data on the presence of depemokimab in breast milk or its effects on the breastfed infant or milk production. Maternal IgG is present in breast milk.

DOSAGE AND ADMINISTRATION — The recommended dosage of depemokimab is 100 mg injected subcutaneously by a healthcare professional in the upper arm, abdomen, or thigh once every 6 months.

CONCLUSION — In patients with severe asthma and elevated eosinophil levels, addition of twice-yearly injections of the interleukin-5 (IL-5) antagonist depemokimab (Exdensur) to background therapy reduced asthma exacerbation frequency, but it did not significantly improve lung function or quality of life. Depemokimab has the advantage of less frequent administration compared to other drugs approved for this indication, but there are no trials directly comparing their efficacy and safety. All of these drugs are expensive.

REFERENCES