Treatment with benralizumab significantly delayed the time to first worsening or flare of symptoms in hypereosinophilic syndrome (HES), based on new data from the NATRON study presented at the American College of Allergy, Asthma, and Immunology (ACAAI) 2025 Annual Meeting.

HES is a rare white blood cell disorder characterized by persistent elevated eosinophils. “While hypereosinophilic syndrome is rare, its impact on patients is significant,” said study author Princess U. Ogbogu, MD, division chief of Pediatric Allergy, Immunology, and Rheumatology at the University Hospitals Rainbow Babies and Children’s Hospital and the Case Western Reserve University, both in Cleveland in an interview.

“Patients can experience a variety of symptoms that lead to poor quality of life, including fatigue, skin issues, GI problems, and pulmonary-related symptoms,” said Ogbogu. Many patients find everyday activities difficult, and new treatment options are needed, she added.

Benralizumab is an anti-IL-5Ra antibody that causes a nearly complete depletion of eosinophils and has demonstrated effectiveness in patients with severe asthma and eosinophilic granulomatosis with polyangiitis, the researchers noted in their abstract.

In the phase 3 study, known as NATRON, Ogbogu and colleagues randomized 133 patients with HES aged 14-87 years to a single 30 mg subcutaneous injection of benralizumab or a placebo, every 4 weeks, plus background therapy, for 24 weeks. Participants had HES flare signs or symptoms at screening or a history of at least two flares in the past year, and all were corticosteroid responsive. The median age of the patients was 51 years, and 62% were women. The primary endpoint was the time to a first HES flare.

At 24 weeks, patients in the benralizumab group had a 65% reduced risk for HES worsening or flare compared to those in the placebo group (19.4% vs 42.4%; hazard ratio, 0.35; P = .0024). In addition, the proportion of patients with flares was significantly lower in the benralizumab group than in the placebo group (22.4% vs 45.5%), as was the annualized flare rate (0.41 vs1.23 flares per year) and the risk for hematologic relapse (hazard ratio, 0.08).

In addition, benralizumab met key secondary endpoints including a significantly greater improvement in PROMIS Fatigue scores compared to placebo (least squared means difference of -4.72; P = .0017).

Rates of adverse events and serious adverse events were similar between the benralizumab and placebo groups (64.2% vs 66.7% and 7.5% vs 7.6%, respectively).

The study results are consistent with an eosinophil-targeted treatment, Ogbogu told Medscape Medical News. “High levels of eosinophils in the blood and tissue contribute to the organ involvement seen in HES; targeting and depleting eosinophils brought patients HES symptom relief, including delaying time to first flare, reducing flare rates, reducing hematologic relapse (AEC [absolute eosinophil count] > 1000 cells/microliter) and reducing fatigue scores,” she said.

The study findings were limited by the small sample size, which also limited the ability to make conclusions based on HES subtype, Ogbogu told Medscape Medical News. “Additional research is needed to study response based on HES subtype and specific-organ involvement,” she said. Long-term observation data will continue to be collected during the open-label extension period of the trial, she added.

However, the results highlight the significant benefits of using eosinophil-targeted therapies such as benralizumab in the care of patients with HES, Ogbogu said.

The study was supported by AstraZeneca. Ogbogu disclosed receiving grant funding from AstraZeneca, Blueprint, DBV Technologies, and GSK and consulting fees from AstraZeneca, Novartis, and BioCryst.