Novel Therapies, New Guidelines Reshape Asthma Management, With Juanita Mora, MD

The severe asthma treatment landscape has been fundamentally transformed by the expansion of biologic therapy options, and the decisions clinicians now face in selecting among them have grown considerably more nuanced — a challenge Juanita Mora, MD, an allergist-immunologist at Chicago Allergy Center and attending physician at Advocate Illinois Masonic Medical Center in Chicago, Illinois, frames as a welcome one in a conversation with HCPLive.

Six FDA-approved biologics are currently available for severe asthma — omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab — with the December 2025 approval of depemokimab (Exdensur, GSK) adding a seventh. Each agent targets a distinct point in the type 2 inflammatory cascade: omalizumab blocks IgE; mepolizumab, reslizumab, and benralizumab target the IL-5 pathway; dupilumab inhibits IL-4 and IL-13 signaling via the IL-4 receptor α chain; and tezepelumab blocks thymic stromal lymphopoietin (TSLP), an upstream alarmin with the broadest applicability across asthma phenotypes. Real-world utilization has shifted markedly in recent years toward dupilumab and tezepelumab, reflecting their broader phenotypic applicability and the growing recognition that TSLP blockade can benefit patients irrespective of eosinophil levels.

Without head-to-head comparative trial data — a persistent gap in the evidence base — Mora relies on a phenotyping-first framework when selecting among agents. Skin testing and specific IgE panels inform identification of allergic asthma phenotypes, where omalizumab remains the established option. Blood eosinophil counts guide selection among anti-IL-5 pathway and anti-TSLP agents. She highlighted the clinical utility of matching biologic choice to coexisting comorbidities: dupilumab, mepolizumab, and omalizumab all carry FDA approval for chronic rhinosinusitis with nasal polyps in addition to asthma, making them preferable single-agent options for patients with that common comorbidity, and dupilumab additionally covers eosinophilic esophagitis — a consideration that often arises in her patient population.

Depemokimab represents a conceptual addition to the severe asthma biologic toolkit beyond just its mechanism. As the first and only biologic for asthma approved with a twice-yearly dosing schedule, it is the first anti-IL-5 antibody engineered with an extended half-life to enable semi-annual administration rather than the every-4-week or every-8-week regimens used by existing agents in the class. In the phase 3 SWIFT-1 and SWIFT-2 trials, depemokimab reduced the annualized asthma exacerbation rate by 58% (rate ratio, 0.42; 95% CI, 0.30–0.59; P <.001) and 48% (rate ratio, 0.52; 95% CI, 0.36–0.73; P <.001), respectively, versus placebo in patients with severe eosinophilic asthma on standard of care. Mora emphasized the access and adherence implications of twice-yearly dosing in particular: for patients with limited transportation, inflexible work schedules, or infrequent health system contact, reducing the injection burden to 2 visits per year may be the practical difference between consistent biologic exposure and treatment dropout.

On inhaler-based management, Mora noted that the field has also undergone a meaningful shift at the step-down end of the treatment spectrum with the broad adoption of SMART (Single Maintenance and Reliever Therapy). Updated Global Initiative for Asthma (GINA) guidelines now recommend against short-acting β₂-agonist (SABA) monotherapy as rescue in asthma, favoring instead a combination inhaled corticosteroid/formoterol regimen that addresses both bronchoconstriction and the underlying airway inflammation driving the acute episode.

“I think the more comfortable we get with this new rescue therapy, using SMART therapy as rescue, we will have a lot more transitioning of our primary care doctors also writing it and getting more patients under better control,” Mora said.

Mora has no relevant disclosures to report.

References

1. Jackson DJ, Busby J, Pfeffer PE, et al. Twice-yearly depemokimab in severe asthma with an eosinophilic phenotype. N Engl J Med. 2024;391:2337-2349. doi:10.1056/NEJMoa2406673

2. GlaxoSmithKline. FDA approves Exdensur (depemokimab-ulaa) for the treatment of severe asthma with an eosinophilic phenotype. Press release. December 16, 2025. https://www.gsk.com/en-gb/media/press-releases/exdensur-depemokimab-approved-by-us-fda-for-the-treatment-of-severe-asthma/

3. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2025 update. https://ginasthma.org