Benralizumab Reduces HES Flare in Phase 3 Trial, With Princess Ogbogu, MD

In an interview with HCPLive, Princess Ogbogu, MD, from the University of Hospitals Rainbow Babies & Children’s Hospital, discussed phase 3 NATRON data showing that benralizumab significantly reduces flare events and fatigue in patients with hypereosinophilic syndrome (HES). These findings, presented at the 2025 American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting, highlight benralizumab’s potential as a safe and effective long-term treatment for this rare eosinophil-driven disorder.

The randomized, double-blind, placebo-controlled trial enrolled patients aged ≥ 12 years across 40 sites in 15 countries. Participants had active, steroid-responsive HES, with at least 2 flares in the previous 2 months and an absolute eosinophil count (AEC) ≥1000 cells/μL. Those with the myeloid subtype of HES were excluded, as they typically respond to tyrosine kinase inhibitors.

Benralizumab, an IL-5 receptor–targeting monoclonal antibody, met its primary endpoint, demonstrating a significantly longer time to first HES flare compared with placebo.

“This is really important because flares are a problem with HDS,” Ogbogu said. “It's a very heterogeneous disease. Patients have a lot of clinical symptoms, and the patients in the benralizumab group really did significantly better than the placebo group, with having reduced risk of flares and reduced flare events.”

The study also achieved its key secondary endpoints, showing a lower annualized flare rate and reduced hematologic relapse, defined as an AEC ≥1000, in patients receiving benralizumab. Improvements in fatigue, measured using the PROMIS Fatigue Score, were observed as early as week 4 and continued through week 24.

Ogbogu noted that safety outcomes were consistent with previous benralizumab trials, with adverse events comparable between treatment and placebo groups. The most common were headache, upper respiratory tract infection, and COVID-19.

“This really adds to the therapies that we know that this is really an important therapy because it's targeting the IL-5 receptor, and we know that this is a very important mechanism for eosinophils and eosinophil-driven disease,” Ogbogu said. “It’s really exciting that there this option may be available for patients.”

Ongoing subgroup analyses and an open-label extension will further evaluate benralizumab’s long-term efficacy and quality-of-life impact in patients with HES.

Relevant disclosures for Ogbogu include Novartis Pharmaceuticals Corporation, AstraZeneca AB, AstraZeneca Pharmaceuticals LP, BioCryst US Sales Co., LLC, GENZYME CORPORATION, Takeda Pharmaceuticals U.S.A., Inc. and Grifols USA, LLC,

References

Ogbogu P. Benralizumab For Patients With Hypereosinophilic Syndrome: A Randomized Double-Blind Placebo-Controlled Phase 3 Trial (NATRON). Late Breaker pesented at ACAAI 2025 on Saturday, November 8, 2025.