Benralizumab Reduces HES Flares in Phase 3 Trial

A phase 3 randomized trial published in Nature Medicine found that add-on benralizumab reduced disease flares compared with placebo in patients with FIP1L1::PDGFRA-negative hypereosinophilic syndrome (HES), according to the study authors.

The NATRON study evaluated benralizumab, an eosinophil-depleting anti-interleukin-5 receptor alpha antibody, in patients with HES. The study authors reported that treatment options for patients with imatinib-insensitive HES are limited, and biologic therapies have expanded available approaches for the disease.

Overall, 134 patients were randomized, and 133 received at least 1 dose of study treatment. Participants were randomly assigned 1:1 to receive benralizumab 30mg every 4 weeks or placebo for 24 weeks, in addition to background HES therapy. The primary endpoint was time to first HES flare during the double-blind treatment period.

HES flare occurred in 13 patients receiving benralizumab and 28 patients receiving placebo. Benralizumab significantly reduced the risk for first flare versus placebo, with a hazard ratio of 0.35 (95% CI, 0.18-0.69; P=.0024). The annualized flare rate was also lower with benralizumab than placebo, at 0.41 versus 1.23 flares per year, respectively.

The proportion of patients experiencing any adverse event was similar between groups. Adverse events occurred in 64.2% of patients receiving benralizumab and 66.7% of those receiving placebo. The authors reported that benralizumab’s safety was consistent with its known profile and concluded that the results support benralizumab as a therapy to manage patients with FIP1L1::PDGFRA-negative HES.

Source: Ogbogu PU, Roufosse F, Akuthota P, et al. Benralizumab versus placebo for hypereosinophilic syndrome: a randomized, placebo-controlled phase 3 trial. Nature Medicine. 2026;32:2017-2025. Published March 31, 2026. doi:10.1038/s41591-026-04315-8