Benralizumab Granted FDA Approval for Patients Aged 12 Years and Older With Hypereosinophilic Syndrome

The FDA approved benralizumab (Fasenra; AstraZeneca) for the treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (HES) without an identifiable nonhematologic secondary cause. The approval is based on positive results from the phase 3 trial NATRON (NCT04191304), according to the news release from AstraZeneca.^1,2

What Are Benralizumab and HES?

Benralizumab is a subcutaneous injection used together with other medicines to treat severe asthma in patients whose asthma is not controlled with their current treatment regimens. It prevents exacerbations and can improve a patient’s breathing by reducing blood eosinophils, or a type of white blood. Additionally, it can be used to treat patients whose asthma has an eosinophilic phenotype and patients with eosinophilic granulomatosis with polyangiitis (EGPA).³

People with HES experience a wide variety of symptoms depending on the organs that are impacted, which can make the disease difficult to diagnose. Symptoms may include weight loss, fever, cough, chest pain, abdominal pain, skin rash, and neurologic symptoms, and over time, HES can lead to organ or tissue damage. The true incidence and prevalence of HES remain unknown, but it is estimated that the prevalence in the US is about 0.3 to 6.3 cases per 100,000 persons.¹

“People living with HES struggle every single day. Debilitating fatigue, risk of organ damage, skin manifestations, and other symptoms adversely impact patients’ lives, making it difficult to maintain normal daily activities, including work. Today’s news brings hope to these people and their families,” Mary Jo Strobel, executive director of the American Partnership for Eosinophilic Disorders, said in the news release.¹

Phase 3 NATRON Clinical Trial

NATRON was a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 study evaluating the efficacy and safety of subcutaneous benralizumab. A total of 133 patients with HES were randomly assigned to receive either 30 mg benralizumab or placebo, and treatment was administered every 4 weeks over a 24-week duration as they continued their stable HES therapy. The trial’s primary efficacy end point was time to first HES worsening or flare, which was defined as HES clinical manifestations or lab abnormalities that result in an increase or burst of oral corticosteroids of 10 mg or more per day for at least 2 days, or an increase or addition of new cytotoxic and/or immunosuppressive therapy or hospitalization.²

Benralizumab Reduces Time to First HES Flare

The trial successfully met the primary end point. Benralizumab reduced time to first HES worsening/flare and significantly reduced the risk of HES worsening/flare compared with placebo by approximately 65% (19.4% vs 42.4% events; HR 0.35 [95% CI, 0.18, 0.69]; P = .0024).⁴

Additionally, all key secondary end points in the trial were also met, as treatment with benralizumab resulted in a fewer number of patients experiencing a flare or withdrawing (22.4% vs 45.5%; odds ratio: 0.31 [95% CI, 0.14, 0.69]; P = .0033) and an approximate 66% reduction in the annualized rate of HES flares (0.41) compared with placebo (1.23; rate ratio: 0.34 [95% CI, 0.18, 0.63]; P = .0008). Time to first hematologic relapse was also delayed for patients receiving benralizumab (hazard ratio: 0.08 [95% CI, 0.03, 0.20]; P < .0001). Patients treated with benralizumab were observed to have a greater improvement in PROMIS fatigue scores by week 4 than those receiving placebo. These persisted to week 24 (least squares mean difference: -4.72 [95% CI, –7.64, –1.80]; P = .0017).⁴

“The approval of benralizumab for the treatment of HES is an important step forward for patients, providing an additional treatment option. The study demonstrated meaningful reduction in flares while addressing fatigue, a symptom that may impact patients,” NATRON principal investigator Princess U. Ogbogu, division chief of pediatric allergy, immunology, and rheumatology at University Hospitals Rainbow Babies and Children’s Hospital and Case Western Reserve University, Cleveland, OH, said in the news release.¹

Common adverse events in patients taking benralizumab may include headache and sore throat in adults and children 6 years and older; headache in adults with EGPA; and headache, allergic reactions, and flu-like symptoms in adults and children aged 12 years and older.¹

“This approval builds on [benralizumab]’s foundation in targeting eosinophilic-driven diseases. [Benralizumab] has been shown to reduce flares in HES, addressing an important need in a population with significant disease burden and few targeted therapies,” James Teague, vice president of US Respiratory & Immunology and Vaccine & Immune Therapies at AstraZeneca, said.¹

REFERENCES

​​1. FASENRA​ approved in ​US​ for ​hypereosinophilic syndrome​. AstraZeneca. News release. May 14, 2026. Accessed May 15, 2026. https://www.astrazeneca-us.com/content/az-us/media/articles/2026/FASENRA-approved-in-US-for-hypereosinophilic-syndrome.html

2. A Phase III Study to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES) (NATRON). ClinicalTrials.gov identifier: NCT04191304. Updated April 2, 2026. Accessed May 15, 2026. https://clinicaltrials.gov/study/NCT04191304

3. Benralizumab (subcutaneous route). Mayo Clinic. Accessed May 15, 2026. https://www.mayoclinic.org/drugs-supplements/benralizumab-subcutaneous-route/description/drg-20406682

4. Statistically significant NATRON Phase III trial results for hypereosinophilic syndrome show Fasenra delayed time to first flare or worsening of disease. AstraZeneca. News release. November 7, 2025. Accessed May 15, 2026. https://www.astrazeneca.com/media-centre/medical-releases/statistically-significant-natron-phase-iii-trial-results-for-hypereosinophilic-syndrome-show-fasenra-delayed-time-to-first-flare-or-worsening-of-disease.html