Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: A randomized clinical trial

• DOI: 10.1016/j.jaci.2021.03.044
• Publication Date: 2021-04-16T22:25:11Z
• Authors: Steven G. Kelsen; Ioana O. Agache; Weily Soong; Elliot Israel; Geoffrey L. Chupp; Dorothy S. Cheung; Wiebke Theess; Xiaoying Yang; Tracy L. Staton; David F. Choy; Alice Fong; Ajit Dash; Michael Dolton; Rajita Pappu; Christopher E. Br...
• Keywords: Safety profile

The IL-33/ST2 pathway is linked with asthma susceptibility. Inhaled allergens, pollutants, and respiratory viruses, which trigger exacerbations, induce release of IL-33, an epithelial-derived "alarmin." Astegolimab, a human IgG2 mAb, selectively inhibits the IL-33 receptor, ST2. Approved biologic therapies for severe mainly benefit patients elevated blood eosinophils (type 2-high), but limited options are available low 2-low). Inhibiting signaling may target pathogenic pathways in wider spectrum asthmatics.This study evaluated astegolimab efficacy safety asthma.This double-blind, placebo-controlled, dose-ranging (ZENYATTA [A Study to Assess Efficacy Safety MSTT1041A Participants With Uncontrolled Severe Asthma]) randomized 502 adults subcutaneous placebo or 70-mg, 210-mg, 490-mg doses every 4 weeks. primary endpoint was annualized exacerbation rate (AER) at week 54. Enrollment caps ensured ∼30 who were eosinophil-high (≥300 cells/μL) ∼95 eosinophil-low (<300 per arm.Overall, adjusted AER reductions relative 43% (P = .005), 22% .18), 37% .01) 490-mg, 70-mg astegolimab, respectively. Adjusted comparable overall population: 54% .002), 14% .48), 35% .05) astegolimab. Adverse events similar astegolimab- placebo-treated groups.Astegolimab reduced broad population patients, including those eosinophil-low, inadequately controlled, asthma. Astegolimab safe well tolerated.