Efficacy of Benralizumab in Eosinophilic Airway Disease: Clinical Insights

NATRON phase 3 update: add-on benralizumab reduced HES flares and lowered annualized flare rate in a corticosteroid-responsive hypereosinophilic syndrome cohort.

According to the phase 3 NATRON trial, add-on benralizumab decreased the proportion of patients with HES flares (22.4% vs 45.5%) and lowered the annualized flare rate (0.41 vs 1.23 flares/year). These numbers suggest more durable disease control and potential steroid-sparing effects.

NATRON was a double-blind, randomized phase 3 add-on trial with time to first HES flare as the primary endpoint and key secondary endpoints that included the proportion of patients with flares and the annualized flare rate. It reports that participants received background therapy plus either benralizumab 30 mg or placebo every 4 weeks for 24 weeks.

PROMIS fatigue scores favored benralizumab (least squares mean difference −4.72; 95% CI −7.64 to −1.80), indicating a measurable patient-reported benefit. Importantly, overall adverse-event rates were similar between groups (AEs 64.2% vs 66.7%; serious AEs 7.5% vs 7.6%) and no new safety signals were identified—tolerability appears consistent with the known profile, so routine monitoring remains prudent.

Clinically, the most plausible candidates for extrapolating these HES results are patients with severe eosinophilic asthma–type phenotypes or steroid-dependent eosinophilic airway disease who have frequent exacerbations or steroid-related adverse effects.

Generalizability is limited because HES cohorts differ from typical asthma populations in pathobiology and endpoints; phenotype-matched selection and shared decision-making should guide any consideration of benralizumab for airway disease.

Key Takeaways:

• The NATRON phase 3 trial showed add-on benralizumab halved the proportion of HES patients who flared and reduced annualized flares from 1.23 to 0.41.
• Patients with severe eosinophilic asthma–like phenotypes or steroid-dependent eosinophilic airway disease with frequent exacerbations are the most likely candidates for benefit.
• Consider phenotype-driven escalation to benralizumab using explicit shared decision-making and monitoring, while recognizing the limitations of HES-to-asthma extrapolation.