Another mAb in the Mix for the Management of Severe Asthma

EBM Focus - Volume 20, Issue 4

Reference: N Engl J Med. 2024 Sep 9

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 retrospectively as having been either uncontrolled despite the use of a recommended drug such as a long-acting beta agonist or a high-dose inhaled corticosteroid or requiring such a drug to achieve control. In about half of patients with severe asthma (termed the “T2-high phenotype”), eosinophils seem to be contributing significantly to the inflammation. The addition of biologic treatments to standard care has already 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 yet another humanized interleukin-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 with severe asthma and high plasma eosinophil counts on medium- to high-potency inhaled steroids and who had ≥ 2 asthma exacerbations needing systemic steroids in the last year were enrolled. Participants were randomized 2:1 to receive either depemokimab or placebo at week 0 and week 26 and were followed for 52 weeks.

Results indicated that depemokimab reduced exacerbations by just over half at 1 year compared to placebo (annualized rate of exacerbations 0.51 vs. 1.11, rate ratio 0.46, 95% CI 0.36-0.59) in 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?

This biologic is ultra-long-acting and is dosed only twice a year (others are dosed monthly, except benralizumab, which is given every 2 months). It isn’t clear if it may be self-administered. Also, costs and coverage may be an issue. 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 an additional option for add-on therapy in adults with severe uncontrolled asthma, one with a clinical advantage of an extended twice-yearly dosing interval, seems handy. With more options, the choice of add-on may not only be dictated by convenience but also by coverage, affordability, coexisting conditions, and patient preference.

For more information, see the topic Biologics for the Treatment of Severe Asthma in DynaMed.

DynaMed EBM Focus Editorial Team

This EBM Focus was written by McKenzie Ferguson, PharmD, BCPS, Senior Clinical Writer at DynaMed. Edited by Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Dan Randall, MD, MPH, FACP, Senior Deputy Editor at DynaMed; Rich Lamkin, MPH, MPAS, PA-C, Clinical Writer at DynaMed; Matthew Lavoie, BA, Senior Medical Copyeditor at DynaMed; Hannah Ekeh, MA, Senior Associate Editor II at DynaMed; and Jennifer Wallace, BA, Senior Associate Editor at DynaMed.