Benralizumab versus placebo for hypereosinophilic syndrome: a randomized, placebo-controlled phase 3 trial
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 .
Authors
- Piotr Kuna (ORCID: https://orcid.org/0000-0003-2401-0070)
- Hanna Grindebacke
- Paneez Khoury (ORCID: https://orcid.org/0000-0003-1800-0079)
- Amy D. Klion (ORCID: https://orcid.org/0000-0002-4986-5326)
- Pim G. N. J. Mutsaers (ORCID: https://orcid.org/0000-0002-3924-8578)
- Gerben Bouma (ORCID: https://orcid.org/0000-0002-1465-9178)
- Princess U. Ogbogu
- Praveen Akuthota (ORCID: https://orcid.org/0000-0001-6655-7520)
- Maria Jison
- Florence Roufosse (ORCID: https://orcid.org/0000-0002-5288-0375)
- Artur Bednarczyk
- R. Palmer (ORCID: https://orcid.org/0000-0002-0827-4706)
- Calvin N. Ho (ORCID: https://orcid.org/0000-0002-3360-9651)
- Lila Bahadori
- Salman H. Siddiqui
- Bing LI
- Matthieu Groh
- Priya Jain
- Akira Yokota
- Laura G. Brooks
- Andreas Reiter
- Jorge Ferreira
Institutions
- AstraZeneca (United Kingdom) (GB)
- National Institutes of Health (US)
- Université Libre de Bruxelles (BE)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Heidelberg University (DE)
- Hammersmith Hospital (GB)
- Erasmus MC (NL)
- University Hospital Heidelberg (DE)
- University of California System (US)
- University of California San Diego (US)
- NIHR Imperial Biomedical Research Centre (GB)
- NIHR Royal Brompton Cardiovascular Biomedical Research Unit (GB)
- Medical University of Lodz (PL)
- National Institute of Allergy and Infectious Diseases (US)
- Chiba Aoba Municipal Hospital (JP)
- AstraZeneca (Poland) (PL)
- AstraZeneca (Finland) (FI)
- AstraZeneca (Sweden) (SE)
- Institute of Hematology & Blood Diseases Hospital (CN)
- AstraZeneca (United States) (US)
- Rainbow Babies & Children's Hospital (US)
Publication Details
- Journal
- Nature Medicine
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1038/s41591-026-04315-8
- Primary Topic
- Eosinophilic Disorders and Syndromes
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Health and Human Services
- AstraZeneca
- National Institute for Health and Care Research
- Department of Health and Social Care
- National Institutes of Health
- NIHR Imperial Biomedical Research Centre