Practice Point: Depemokimab reduces asthma exacerbations in patients with severe asthma and high eosinophil count.
EBM Pearl: Replicate studies are identical trials conducted as a pair to allow for easy pooling of data and the ability to measure consistency from one to the other, saving a step in validating results.
Asthma affects millions of adults and children and creates substantial health and economic impacts for patients, caregivers, and the health care system. Severe asthma is defined by GINA 2023 as having been either (a) uncontrolled despite the use of a recommended drug (such as a long-acting beta agonist or a high-dose inhaled corticosteroid) or (b) requiring such a drug to achieve control. In about half of patients with severe asthma, eosinophils seem to be contributing substantially to the inflammation (termed the “T2-high phenotype”). The addition of biologic treatments to standard care has helped many patients with severe, uncontrolled asthma breathe easier, so how does depemokimab differ from all the other monoclonal antibodies (mAbs) out there?
Depemokimab is another humanized interleukin-5 (IL-5) antagonist monoclonal antibody (there are at least 12 other biologic agents studied or approved for asthma) dosed at 100 mg subcutaneously every 26 weeks. Investigators conducted two multinational identical (“replicate”) randomized placebo-controlled trials (SWIFT-1 and SWIFT-2) to evaluate the efficacy and safety of depemokimab. In total, 762 adults and 30 adolescents were enrolled. They had severe asthma and high plasma eosinophil counts on medium- to high-potency inhaled steroids and at least two asthma exacerbations needing systemic steroids in the last year. Participants were randomized two:one to receive either depemokimab or placebo at week zero and week 26 and were followed for 52 weeks.
Results indicated that depemokimab reduced exacerbations by just over half at one year compared to placebo (annualized rate of exacerbations 0.51 vs. 1.11, rate ratio 0.46, 95% CI 0.36-0.59) in the pooled analysis. However, there was no meaningful impact on quality of life demonstrated in these trials, even though trials of other biologics such as omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab have shown improved quality of life.
So, what’s the appeal for this additional me-too mAb?
Depemokimab is ultra-long-acting and given only twice per year, whereas other biologics are dosed monthly, except for benralizumab, which is given every two months. It isn’t clear if depemokimab could be self-administered. The most common adverse events were COVID-19 (15%-22%), nasopharyngitis (12%-21%), upper respiratory tract infection (5%-11%), and headache (5%-8%), but no anaphylaxis or type III hypersensitivity reactions were reported.
Depemokimab is an investigational drug (not yet FDA approved). But it may be an option for add-on therapy in adults with severe, uncontrolled asthma, and it has the clinical advantage of an extended twice-yearly dosing schedule. With more options, however, choosing an add-on such as depemokimab may not only be dictated by convenience but also by insurance coverage, affordability, coexisting conditions, and patient preferences.
For more information, see the topic Biologics for the Treatment of Severe Asthma in DynaMedex.
Reference: N Engl J Med. 2024 Sep 9
