The NATRON clinical trial was a 24-week, randomized, double-blind, placebo-controlled, Phase 3 study comparing the efficacy and safety of FASENRA to placebo in patients aged 12 years and older who had signs or symptoms of HES flare or had experienced at least 2 HES flares within the past 12 months.1,2 See the full study design.

Primary endpoint: Time to first HES flare by Week 24*†1,2

Chart Illustrating Key Study Design Elements of the 24‑Week NATRON Phase 3 Clinical Trial In HES Chart Illustrating Key Study Design Elements of the 24‑Week NATRON Phase 3 Clinical Trial In HES

SIGNIFICANT

65%

REDUCTION IN RISKOF FIRST FLARE

(HR: 0.35; 95% CI: 0.18-0.69; P=0.0024)

HES flare: clinical manifestation or laboratory abnormality leading to increase/addition of OCS (≥10 mg/day prednisolone equivalent for ≥2 days) OR cytotoxic and/or immunosuppressive HES therapy; OR hospitalization.

Secondary endpoint: Annualized rate of HES flares1,2

66%

REDUCTION IN ANNUALIZED FLARE RATE

0.41 with FASENRA vs 1.23 with placebo (RR: 0.34; 95% Cl: 0.18-0.63; P=0.0008)*1,2

81% of patients experienced ZERO FLARES (vs 58% for placebo)1

Results are descriptive only.

HES flare: clinical manifestation or laboratory abnormality leading to increase/addition of OCS (≥10 mg/day prednisolone equivalent for ≥2 days) OR cytotoxic and/or immunosuppressive HES therapy; OR hospitalization.

AIM TO ADDRESS OCS OVEREXPOSURE

Secondary endpoint: Proportion of patients experiencing HES flares resulting in an increase in oral corticosteroid (OCS) dose during the double-blind treatment period1

Bar chart comparing patient percentages in the NATRON HES trial, showing 42% for placebo and 18% for Fasenra, with sample sizes n=28/66 and n=12/67. Bar chart comparing patient percentages in the NATRON HES trial, showing 42% for placebo and 18% for Fasenra, with sample sizes n=28/66 and n=12/67.

~60% FEWER PATIENTS NEEDED AN OCS BURST

to treat flares‡§

Results are descriptive only.

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. Decrease corticosteroids gradually, if appropriate.

FLARE/OCS DATA FAQs

NATRON was a 24-week randomized, double-blind, parallel-group, placebo-controlled clinical trial that evaluated the efficacy and safety of FASENRA in patients 12 and older with HES. A total of 133 adult and adolescent patients who had signs or symptoms of HES flare or had experienced at least 2 HES flares within the past 12 months received randomized treatment. Patients were randomized to FASENRA 30 mg or placebo administered subcutaneously every 4 weeks while continuing their stable HES therapy.1,2

References: 1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2026. 2. Ogbogu PU, Roufosse F, Akuthota P, et al. Benralizumab versus placebo for hypereosinophilic syndrome: a randomized, placebo-controlled phase 3 trial. Nat Med. Published online March 31, 2026. doi:10.1038/s41591-026-04315-8

The primary endpoint of the NATRON study was the time to first flare during the double-blind period.1,2

An HES flare was defined as a clinical manifestation or laboratory abnormality leading to increase/addition of OCS (≥10 mg/day prednisolone equivalent for ≥2 days), or cytotoxic and/or immunosuppressive HES therapy, or hospitalization.1,2

Key secondary endpoints included1,2:

  • Proportion of patients who experienced an HES flare during the treatment period
  • Rate of HES flares
  • Change from baseline in fatigue severity

References: 1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2026. 2. Ogbogu PU, Roufosse F, Akuthota P, et al. Benralizumab versus placebo for hypereosinophilic syndrome: a randomized, placebo-controlled phase 3 trial. Nat Med. Published online March 31, 2026. doi:10.1038/s41591-026-04315-8

In NATRON, an HES flare was defined as a clinical manifestation or laboratory abnormality leading to: an increase/addition of OCS (≥10 mg/day prednisolone equivalent for ≥2 days) OR cytotoxic and/or immunosuppressive HES therapy; OR hospitalization.1,2

References: 1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2026. 2. Ogbogu PU, Roufosse F, Akuthota P, et al. Benralizumab versus placebo for hypereosinophilic syndrome: a randomized, placebo-controlled phase 3 trial. Nat Med. Published online March 31, 2026. doi:10.1038/s41591-026-04315-8

*For patients who did not experience an HES worsening/flare, the time to first HES worsening/flare was right censored at the end of the double-blind period corresponding to the earliest date of: the first FASENRA open-label dose, study Day 183, date of last contact, and data cut-off date.2

†Any patients who withdrew from the study without having flared (placebo, n=2; FASENRA, n=2) are included in the analysis as if they had flared.1,2

‡An increase of OCS ≥10 mg/day (prednisone/prednisolone equivalent) for at least 2 days.2

§The number of times a patient required a corticosteroid increase/burst was counted as a separate incidence if the start date of the increase/burst was at least 14 days after the start date of the previous increase/burst.3

CI, confidence interval; HR, hazard ratio; OCS, oral corticosteroid; RR, rate ratio.