FASENRA is indicated for the add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma, and with an eosinophilic phenotype. FASENRA is not for the relief of acute bronchospasm or status asthmaticus.

Cookie Icon

Real-World Effectiveness Study of Benralizumab
for Severe Eosinophilic Asthma: ZEPHYR 2

Real-World Effectiveness Study of Benralizumab for Severe Eosinophilic Asthma: ZEPHYR 2

In the SIROCCO (48 weeks) pivotal trial, a 51% reduction in annual asthma exacerbation rate was observed in patients treated with FASENRA + SOC (n=267) vs placebo + SOC (n=267) (0.74 vs 1.52, P<0.0001). In CALIMA (56 weeks), a 28% reduction in annual asthma exacerbation rate was observed in patients treated with FASENRA + SOC (n=239) vs placebo + SOC (n=248) (0.73 vs 1.01, P=0.019).1-3

Information for Healthcare
Professionals

Real-World Effectiveness Study of Benralizumab for Severe Eosinophilic Asthma: ZEPHYR 2

Carstens D, Maselli DJ, Mu F, et al. J Allergy Clin Immunol Pract. 2023;11(7):2150-2161.e4.

The linked reprint discusses some information about FASENRA® (benralizumab) injection, for subcutaneous use that is not contained in its FDA-approved Prescribing Information. AstraZeneca manufactures FASENRA and provided sponsorship/funding for the study discussed in this reprint. Some authors may have a financial interest in either FASENRA or AstraZeneca and may have received compensation from AstraZeneca in connection with this study or other engagements. AstraZeneca recommends use of FASENRA only in accordance with its approved Prescribing Information.

Real-world data on the clinical impact of benralizumab in various patient populations such as patients with varying eosinophil levels, previous biologic use, and extended follow-up in the United States are limited.

The objective of the ZEPHYR 2 study was to understand the real-world effectiveness of benralizumab in different asthma patient cohorts and its long-term clinical impact.

Key Study Limitations

  • This is an observational study; clinical implications cannot be determined from this payer database study

  • There was no control population (ie, with no benralizumab treatment), the pre–post analysis did not include a control for changes that may have occurred over time in the absence of benralizumab

  • The current findings may only be generalizable to patients on therapy for 12 or 24 months based on individual cohorts

  • The use of ICD codes to identify diagnoses may result in misclassification as there may be inaccuracies in the recording of ICD codes by physicians. However, to avoid misclassification in the study population, patients were required to have a record of use of an asthma-specific treatment and multiple asthma exacerbations prior to benralizumab initiation

  • Some variables of interest such as eosinophil laboratory values or IgE levels were not available for all patients, and others such as reason for switching treatments or smoking history were not available for any patient. Additional studies examining the impact of benralizumab on these variables in the real world would be beneficial

  • Claims data do not capture first-dose samples of benralizumab provided to patients that may have influenced pre- and post-benralizumab asthma exacerbation rates and other outcomes

Click to Read
ZEPHYR 2 Study Reprint

Click to Read
ZEPHYR 2 Study Reprint

Zephyr 2 study icon

Study Designs

SIROCCO AND CALIMA (Trials 1 and 2)

SIROCCO (48 weeks) and CALIMA (56 weeks) were 2 randomized, double-blind, parallel-group, placebo-controlled, multicenter studies comparing FASENRA 30 mg SC Q4W for the first 3 doses, then Q8W thereafter; benralizumab 30 mg SC Q4W; and placebo SC. A total of 1204 (SIROCCO) and 1306 (CALIMA) patients aged 12-75 years old with severe asthma uncontrolled on high-dose ICS (SIROCCO) and medium- to high-dose ICS (CALIMA) plus LABA with or without additional controllers were included. Patients had a history of ≥2 exacerbations requiring systemic corticosteroids or temporary increase in usual dosing in the previous year. Patients were stratified by geography, age, and bEOS counts (≥300 cells/μL and <300 cells/μL). The primary endpoint was annual exacerbation rate ratio vs placebo in patients with bEOS counts of ≥300 cells/μL on high-dose ICS and LABA. Exacerbations were defined as a worsening of asthma that led to use of systemic corticosteroids for ≥3 days, temporary increase in a stable OCS background dose for ≥3 days, emergency/urgent care visit because of asthma that needed systemic corticosteroids, or inpatient hospital stay of ≥24 hours because of asthma. Key secondary endpoints were prebronchodilator FEV1 and total asthma symptom score at Week 48 (SIROCCO) and Week 56 (CALIMA) in the same population.

IMPORTANT SAFETY INFORMATION -

CONTRAINDICATIONS

Known hypersensitivity to benralizumab or excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA. These reactions generally occur within hours of administration, but in some instances have a delayed onset (ie, days). Discontinue in the event of a hypersensitivity reaction.

Acute Asthma Symptoms or Deteriorating Disease

FASENRA should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.

Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection

It is unknown if FASENRA will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with FASENRA. If patients become infected while receiving FASENRA and do not respond to anti-helminth treatment, discontinue FASENRA until infection resolves.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥ 5%):

  • Asthma: headache, pharyngitis
  • EGPA: headache
  • HES: headache, hypersensitivity reactions, influenza-like illness

Injection site reactions (eg, pain, erythema, pruritus, papule) occurred at a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treated with placebo in asthma exacerbation studies.

USE IN SPECIFIC POPULATIONS

A pregnancy exposure registry monitors pregnancy outcomes in women exposed to FASENRA during pregnancy. To enroll call 1-877-311-8972 or visit www.mothertobaby.org/fasenra.

The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy.

INDICATIONS

FASENRA is indicated for:

  • the add-on maintenance treatment of patients with severe asthma aged 6 years and older and with an eosinophilic phenotype. FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus
  • the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA)
  • the treatment of adult and adolescent patients aged 12 years and older with hypereosinophilic syndrome (HES) without an identifiable non-hematologic secondary cause

Please read full Prescribing Information, including Patient Information.

Please read full Prescribing Information, including Patient Information.

You may report side effects related to AstraZeneca products .

IMPORTANT SAFETY INFORMATION

 +

References

Reference

1. Data on File, US-107034, AZPLP. 2. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2026. 3. Bleecker ER, FitzGerald JM, Chanez P, et al; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-2127. 4. FitzGerald JM, Bleecker ER, Nair P, et al; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128-2141.

 

1. Korn S, Bourdin A, Chupp G, et al. Integrated safety and efficacy among patients receiving benralizumab for up to 5 years. J Allergy Clin Immunol Pract. 2021;9(12):4381-4392.e4.

1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; September 2024. 2. Laviolette M, Gossage DL, Gauvreau G, et al. Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol. 2013;132(5):1086-1096.e5.

1. Data on File, REF-51332, AZPLP. 2. Bleecker ER, FitzGerald JM, Chanez P, et al; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting ß2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-2127. 3. Skolnik NS, Carnahan SP. Primary care of asthma: new options for severe eosinophilic asthma. Curr Med Res Opin. 2019;35(7):1309-1318. 4. Tran TN, Zeiger RS, Peters SP, et al. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann Allergy Asthma Immunol. 2016;116(1):37-42.

1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; September 2024. 2. Bleecker ER, FitzGerald JM, Chanez P, et al; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting ß2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-2127. 3. FitzGerald JM, Bleecker ER, Nair P, et al; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128-2141. 4. Chipps BE, Newbold P, Hirsch I, Trudo F, Goldman M. Benralizumab efficacy by atopy status and serum immunoglobulin E for patients with severe, uncontrolled asthma. Ann Allergy Asthma Immunol. 2018;120(5):504-511.e4.

1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; September 2024. 2. Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376(25):2448-2458. 3. Menzies-Gow A, Corren J, Bel EH, et al. Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE trial. ERJ Open Res. 2019;5(3):00009-2019. 4. Menzies-Gow A, Gurnell M, Heaney LG, et al. Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study. Lancet Respir Med. 2022;10(1):47-58. 5. Menzies-Gow A, Gurnell M, Heaney LG, et al. Adrenal function recovery after durable oral corticosteroid sparing with benralizumab in the PONENTE study. Eur Respir J. 2022;60(6):2103226.

1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; September 2024. 2. Bleecker ER, FitzGerald JM, Chanez P, et al; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting ß2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-2127. 3. FitzGerald JM, Bleecker ER, Nair P, et al; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128-2141. 4. Busse WW, Bleecker ER, FitzGerald JM, et al; BORA study investigators. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir Med. 2019;7(1):46-59. 5. FitzGerald JM, Bleecker ER, Bourdin A, et al. Two-year integrated efficacy and safety analysis of benralizumab in severe asthma. J Asthma Allergy. 2019;12:401-413. 6. Data on File, REF-19697, AZPLP. 7. Data on File, REF-59636, AZPLP. 8. Chipps BE, Hirsch I, Trudo F, et al. Benralizumab efficacy for patients with fixed airflow obstruction and severe, uncontrolled eosinophilic asthma. Ann Allergy Asthma Immunol. 2020;124(1):79-86. 9. Kaminska M, Foley S, Maghni K, et al. Airway remodeling in subjects with severe asthma with or without chronic persistent airflow obstruction. J Allergy Clin Immunol. 2009;124(1):45-51.e1-4. 10. Rutting S, Thamrin C, Cross TJ, King GG, Tonga KO. Fixed airflow obstruction in asthma: a problem of the whole lung not of just the airways. Front Physiol. 2022;13:898208.

1. Skolnik NS, Carnahan SP. Primary care of asthma: new options for severe eosinophilic asthma. Curr Med Res Opin. 2019;35(7):1309-1318. 2. Global Initiative for Asthma. 2025 GINA Report, Global Strategy for Asthma Management and Prevention. Accessed May 27, 2025. https://ginasthma.org/reports 3. Bleecker ER, FitzGerald JM, Chanez P, et al; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-2127. 4. Tran TN, Zeiger RS, Peters SP, et al. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann Allergy Asthma Immunol. 2016;116(1):37-42.

1. Data on File, US-94507, AZPLP.

1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; April2024 .

1. Data on File, REF-211303, AZPLP. 2. Jackson DJ, Pelaia G, Emmanuel B, et al. Benralizumab in severe eosinophilic asthma by previous biologic use and key clinical subgroups: real-world XALOC-1 programme. Eur Respir J. 2024;64(1):2301521. 3. Carstens D, Maselli DJ, Mu F, et al. Real-world effectiveness study of benralizumab for severe eosinophilic asthma: ZEPHYR 2. J Allergy Clin Immunol Pract. 2023;11(7):2150-2161.e4. 4. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; September 2024. 5. Bleecker ER, FitzGerald JM, Chanez P, et al; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting ß2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-2127. 6. Penz E, Rothe T, Dupont L, et al. Early and sustained asthma control and remission in real-world patients with severe eosinophilic asthma treated with benralizumab: XALOC-2. Clin Exp Allergy. Published online October 29, 2025. doi:10.1111/cea.70162 7. Penz E, Rothe T, Dupont L, et al. Early and sustained asthma control and remission in real-world patients with severe eosinophilic asthma treated with benralizumab: XALOC-2. Supplemental materials. Clin Exp Allergy. Published online October 29, 2025. doi:10.1111/cea.70162

1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; September 2024. 2. Bleecker ER, FitzGerald JM, Chanez P, et al; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting ß2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-2127. 3. FitzGerald JM, Bleecker ER, Nair P, et al; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128-2141. 4. Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376(25):2448-2458. 5. Busse WW, Bleecker ER, FitzGerald JM, et al; BORA study investigators. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir Med. 2019;7(1):46 -59. 6. Korn S, Bourdin A, Chupp G, et al. Integrated safety and efficacy among patients receiving benralizumab for up to 5 years. J Allergy Clin Immunol Pract. 2021;9(12):4381-4392.e4. 7. Menzies-Gow A, Gurnell M, Heaney LG, et al. Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study. Lancet Respir Med. 2022;10(1):47-58. 8. Menzies-Gow A, Corren J, Bel EH, et al. Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE trial. ERJ Open Res. 2019;5(3):00009-2019. 9. Menzies-Gow A, Gurnell M, Heaney LG, et al. Adrenal function recovery after durable oral corticosteroid sparing with benralizumab in the PONENTE study. Eur Respir J. 2022;60(6):2103226. 10. Data on File, REF -211303, AZPLP. 11. Jackson DJ, Pelaia G, Emmanuel B, et al. Benralizumab in severe eosinophilic asthma by previous biologic use and key clinical subgroups: real-world XALOC-1 programme. Eur Respir J. 2024;64(1):2301521. 12. Carstens D, Maselli DJ, Mu F, et al. Real-world effectiveness study of benralizumab for severe eosinophilic asthma: ZEPHYR 2. J Allergy Clin Immunol Pract. 2023;11(7):2150-2161.e4. 13. Penz E, Rothe T, Dupont L, et al. Early and sustained asthma control and remission in real-world patients with severe eosinophilic asthma treated with benralizumab: XALOC-2. Clin Exp Allergy. Published online October 29, 2025. doi:10.1111/cea.70162 14. Penz E, Rothe T, Dupont L, et al. Early and sustained asthma control and remission in real-world patients with severe eosinophilic asthma treated with benralizumab: XALOC-2. Supplemental materials. Clin Exp Allergy. Published online October 29, 2025. doi:10.1111/cea.70162

1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; September 2024. 2. Korn S, Bourdin A, Chupp G, et al. Integrated safety and efficacy among patients receiving benralizumab for up to 5 years. J Allergy Clin Immunol Pract. 2021;9(12):4381-4392.e4. 3. Data on File, US-103275, AZPLP. 4. ClinicalTrials.gov [Internet]. National Library of Medicine (US). Identifier NCT00783289 ClinicalTrials.gov website. Accessed July 10, 2025. https://clinicaltrials.gov/ct2/show/NCT00783289

1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; September 2024. 2. Ferguson GT, Cole J, Aurivillius M, Roussel P, Barker P, Martin UJ; GRECO study investigators. Single-use autoinjector functionality and reliability for at-home administration of benralizumab for patients with severe asthma: GRECO trial results. J Asthma Allergy. 2019;12:363-373.

1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; April 2024. 2. Bleecker ER, FitzGerald JM, Chanez P, et al; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting ß2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-2127. 3. FitzGerald JM, Bleecker ER, Nair P, et al; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128-2141.

1. Formulary data are provided by Fingertip Formulary® and are current as of October 6, 2025.