2. Academic Validation
  3. Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: A randomized clinical trial

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

  • J Allergy Clin Immunol. 2021 Sep;148(3):790-798. doi: 10.1016/j.jaci.2021.03.044.
Steven G Kelsen 1,  Ioana O Agache 2,  Weily Soong 3,  Elliot Israel 4,  Geoffrey L Chupp 5,  Dorothy S Cheung 6,  Wiebke Theess 6,  Xiaoying Yang 6,  Tracy L Staton 6,  David F Choy 6,  Alice Fong 6,  Ajit Dash 6,  Michael Dolton 6,  Rajita Pappu 6,  Christopher E Brightling 7
Affiliations

Affiliations

  • 1 Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, Pa.
  • 2 Allergy and Clinical Immunology, Faculty of Medicine, Transylvania University, Brasov, Romania.
  • 3 Alabama Allergy and Asthma Center and Clinical Research Center of Alabama, Birmingham, Ala.
  • 4 Divisions of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass.
  • 5 Division of Pulmonary and Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Conn.
  • 6 Genentech, Inc., South San Francisco, Calif.
  • 7 Department of Respiratory Sciences, University of Leicester, Leicestershire, United Kingdom. Electronic address: [email protected].
PMID: 33872652 DOI: 10.1016/j.jaci.2021.03.044
Abstract

Background: The IL-33/ST2 pathway is linked with asthma susceptibility. Inhaled allergens, pollutants, and respiratory viruses, which trigger asthma 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 asthma mainly benefit patients with elevated blood eosinophils (type 2-high), but limited options are available for patients with low blood eosinophils (type 2-low). Inhibiting IL-33 signaling may target pathogenic pathways in a wider spectrum of asthmatics.

Objectives: This study evaluated astegolimab efficacy and safety in patients with severe asthma.

Methods: This double-blind, placebo-controlled, dose-ranging study (ZENYATTA [A Study to Assess the Efficacy and Safety of MSTT1041A in Participants With Uncontrolled Severe Asthma]) randomized 502 adults with severe asthma to subcutaneous placebo or 70-mg, 210-mg, or 490-mg doses of astegolimab every 4 weeks. The primary endpoint was the annualized asthma exacerbation rate (AER) at week 54. Enrollment caps ensured ∼30 patients who were eosinophil-high (≥300 cells/μL) and ∼95 patients who were eosinophil-low (<300 cells/μL) per arm.

Results: Overall, adjusted AER reductions relative to placebo were 43% (P = .005), 22% (P = .18), and 37% (P = .01) for 490-mg, 210-mg, and 70-mg doses of astegolimab, respectively. Adjusted AER reductions for patients who were eosinophil-low were comparable to reductions in the overall population: 54% (P = .002), 14% (P = .48), and 35% (P = .05) for 490-mg, 210-mg, and 70-mg doses of astegolimab. Adverse events were similar in astegolimab- and placebo-treated groups.

Conclusions: Astegolimab reduced AER in a broad population of patients, including those who were eosinophil-low, with inadequately controlled, severe asthma. Astegolimab was safe and well tolerated.

Keywords

IL-33; ST2; asthma exacerbations; eosinophils; severe asthma.

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