Benralizumab versus placebo for hypereosinophilic syndrome: a randomized, placebo-controlled phase 3 trial
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Benralizumab, an eosinophil-depleting anti-IL-5 receptor α antibody, has demonstrated efficacy in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis and shown promising results in hypereosinophilic syndrome (HES). NATRON was a randomized, double-blind placebo-controlled phase 3 study evaluating the efficacy and safety of benralizumab in FIP1L1::PDGFRA-negative HES. The primary endpoint was time to first HES flare. In total, 133 patients (median (range) age 51 (14–87) years, 62% female) were randomized (1:1) to receive benralizumab 30 mg every 4 weeks or placebo for 24 weeks, in addition to background therapy. Benralizumab significantly reduced the risk of first flare versus placebo (hazard ratio 0.35, 95% CI 0.18 to 0.69, P = 0.0024). Adverse events occurred in 64.2% and 66.7% of benralizumab- and placebo-treated patients, respectively. Benralizumab’s safety was consistent with its known profile. These results demonstrate the efficacy and safety of add-on benralizumab in the treatment of HES. ClinicalTrials.gov identifier: NCT04191304.
Date Issued
2026-06-01
Date Acceptance
2026-03-02
Citation
Nature Medicine, 2026, 32 (6), pp.2017-2025
ISSN
1078-8956
Publisher
Springer Science and Business Media LLC
Start Page
2017
End Page
2025
Journal / Book Title
Nature Medicine
Volume
32
Issue
6
Copyright Statement
This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2026, modified publication 2026 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons. org/licenses/by/4.0/
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41917160
PII: 10.1038/s41591-026-04315-8
Subjects
Humans
Female
Hypereosinophilic Syndrome
Antibodies, Monoclonal, Humanized
Middle Aged
Double-Blind Method
Adult
Aged
Adolescent
Male
Aged, 80 and over
Young Adult
Treatment Outcome
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2026-03-31