The Evolving Role of Biologics and TSLP Inhibition in Severe Asthma and Upper Airway Disease - Episode 11
Biologics for Severe Asthma: Targets, Timing, and Outcomes
Seven approved agents across four targets, spanning two decades of approvals. Dr. Wechsler maps the class, then names the 40% of exacerbations it still does not prevent.
In "Seven Biologics for Severe Asthma: Targets, Timing, and Outcomes," the panel steps back for a full survey of the treatment landscape.
Dr. Chupp calls for a setup on the toolbox available, and Dr. Wechsler delivers the overview. He starts with contrast: 25 to 30 years ago the options were inhaled steroids, bronchodilators, and perhaps leukotriene modifiers. Today there are seven biologics approved for severe asthma, best understood by pathway.
Anti-IgE came first, approved in 2003, important for allergic asthma and later shown effective in urticaria and food allergy. Nothing followed until 2015, when agents targeting IL-5 arrived, then the IL-5 receptor, rolling out across 2015, 2016, and 2017 and proving very effective specifically in eosinophilic asthma. In 2025 the next generation arrived: an ultra-long-acting anti-IL-5 given just twice a year, against comparators dosed every two, four, or eight weeks, reducing exacerbations by over 50%.
Next is anti-IL-4 receptor therapy, which blocks both IL-4 and IL-13. It was approved first in atopic dermatitis in 2017, then in asthma in 2018 for severe, steroid-dependent, and type 2 phenotypes, and has since proved effective in chronic sinusitis and eosinophilic esophagitis. Two agents have crossed into eosinophilic COPD. The last class blocks TSLP. Tezepelumab has been available about five years, and works upstream, blocking downstream TH2 and ILC2 activation of IL-4, IL-5, and IL-13.
Dr. Wechsler names what the class shares. All reduce exacerbations well. All generally improve symptoms, lung function, steroid burden, and quality of life. Some patients reach remission, which he calls the next goal. Then the caveat: they are not perfect. They reduce exacerbations by 50% to 60%, leaving 40% to 50% unaddressed. They are safe, but he argues for better biomarkers, more targeted approaches, and head-to-head studies.
Our next episode, "Positioning Biologics in Asthma: GINA Step 5 and Earlier Treatment," asks Dr. Hanania where these agents belong in the treatment paradigm.
