UNIQUE MECHANISM OF ACTION1,2

FASENRA is the only anti-eosinophil that binds directly at the surface of the eosinophil1

Fasenra Mechanism of Action Fasenra Mechanism of Action

The mechanism of action of benralizumab in asthma has not been definitively established.

PHARMACODYNAMICS

Rapid near complete depletion of blood eosinophils with FASENRA*1-3

24 Hours Icon

FASENRA is the first and only anti-eosinophil biologic that provides near complete depletion of blood eosinophils in 24 hours*1-3

The relationship between the pharmacologic properties and clinical efficacy has not been established.

Two Years Icon

In BORA (Phase 3 Safety Extension Trial of SIROCCO and CALIMA), median blood eosinophils started at 0 and remained at 0.0 cells/µL in Year 2 of treatment†4,5

EXPLORE SAFETY

Patients who received FASENRA in ZONDA (Trial 3) had decreased median sputum eosinophils from 4.90% (n=18) at baseline to 0.15% (n=8) at treatment end.‡6

In ZONDA, FASENRA and placebo were administered in addition to daily OCS (7.5 to 40 mg) + SOC, which was defined as high-dose ICS/LABA with or without other controllers.1 In BORA, patients from SIROCCO and CALIMA (Trials 1 and 2) were randomized to continue FASENRA administered at the same dose or re-randomized from placebo to 1 of 2 doses of FASENRA.4

Please see full study descriptions for SIROCCO, CALIMA, ZONDA, a phase 2 study, and BORA.

ICS=inhaled corticosteroids; LABA=long-acting β2-agonists; OCS=oral corticosteroids; SOC=standard of care.

*The pharmacodynamic response (blood eosinophil depletion) following repeat subcutaneous (SC) dosing was evaluated in asthma patients in a 12-week phase 2 trial. Patients received 1 of 3 doses of benralizumab [25 mg (n=6), 100 mg (n=6) or 200 mg (n=6) SC] or placebo (n=6) every 4 weeks for a total of 3 doses. Twenty-four hours post dosing, all benralizumab dosage groups demonstrated complete or near complete depletion of median blood eosinophil levels, which was maintained throughout the dosing period.1-3

At baseline of the BORA trial, in patients with baseline blood eosinophil counts ≥300 cells/μL in SIROCCO and CALIMA who continued on FASENRA every 8 weeks (n=339), the median EOS level was 0 cells/μL, which was maintained through Week 56.4,5

The effect of the treatment on sputum eosinophils was evaluated in a sub-study of ZONDA. Patients were randomized to receive benralizumab 30 mg SC every 4 weeks (Q4W), every 8 weeks (Q8W; first 3 doses Q4W) or placebo Q4W. In a combined analysis of the benralizumab 30 mg Q4W and Q8W groups, median sputum eosinophils were depleted for patients treated with benralizumab from 4.90% (n=18) at baseline to 0.0% (n=16) at Week 12, and 0.15% (n=8) at Week 28. For patients who received placebo, median sputum eosinophil counts increased from 4.90% (n=8) at baseline to 17.55% (n=4) at Week 12 and 12.15% (n=4) at Week 28. Results are descriptive only.6

INDICATION

FASENRA is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype.

  • FASENRA is not indicated for treatment of other eosinophilic conditions
  • FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus

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.

INDICATION

FASENRA is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype.

  • FASENRA is not indicated for treatment of other eosinophilic conditions
  • FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥ 5%) include headache and pharyngitis.

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.

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.

Please read full Prescribing Information, including Patient Information.

You may report side effects related to AstraZeneca products by clicking here.

References: 1. FASENRA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; October 2019. 2. Bleecker ER, FitzGerald JM, Chanez P, et al. 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;388:2115-2127. 3. FitzGerald JM, Bleecker ER, Nair P, et al. 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;388:2128-2141. 4. FitzGerald JM, Bleecker ER, Bourdin A, et al. Two-year integrated efficacy and safety analysis of benralizumab SIROCCO, CALIMA, ZONDA, and BORA trials in severe asthma. Presented at: the American Thoracic Society (ATS) International Conference; May 17-22, 2019; Dallas, TX. 5. Busse WW, Bleecker ER, FitzGerald JM, et al. 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;7:46-59. 6. Data on File, REF-51332, AZPLP. 7. Pham TH, Damera G, Newbold P, Ranade K. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016;111:21-29. 8. Data on File, REF-28001, AZPLP.

References: 1. FASENRA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; October 2019. 2. Pham TH, Damera G, Newbold P, Ranade K. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016;111:21-29. 3. Data on File, REF-28001, AZPLP. 4. Busse WW, Bleecker ER, FitzGerald JM, et al. 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;7:46-59. 5. Busse WW, Bleecker ER, FitzGerald JM, et al. Supplementary Appendix to: 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;7:46-59. 6. Nair P, Wenzel S, Rabe KF, et al. Supplementary Appendix to: Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448-2458.

References: 1. Data on File, REF-51332, AZPLP. 2. de Groot JC, Storm H, Amelink M, et al. Clinical profile of patients with adult-onset eosinophilic asthma. ERJ Open Res. 2016;2(2):00100-2015. 3. de Groot JC, ten Brinke A, Bel EH. Management of the patient with eosinophilic asthma: a new era begins. ERJ Open Res. 2015;1:00024-2015. 4. Price DB, Rigazio A, Campbell JD, et al. Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respir Med. 2015;3:849-858. 5. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2019. https://ginasthma.org/wp-content/uploads/2019-main-report-June-2019-wms.pdf. 6. Skolnik NS, Carnahan SP. Primary care of asthma: new options for severe eosinophilic asthma. Curr Med Res Opin. 2019;35:1309-1318. 7. 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. 8. Carr TF, Berdnikovs S, Simon H-U, et al. Eosinophilic bioactivities in severe asthma. World Allergy Organ J. 2016;9:21. 9. Ortega H, Llanos J-P, Lafeuille M-H, et al. Effects of systemic corticosteroids on blood eosinophil counts in asthma: real-world data. J Asthma. 2019;56(8):808-815. 10. FASENRA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; October 2019.

References: 1. Data on File, REF-60828, AZPLP. 2. FASENRA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; October 2019. 3. Bleecker ER, FitzGerald JM, Chanez P, et al. 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;388:2115-2127. 4. FitzGerald JM, Bleecker ER, Nair P, et al. 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;388:2128-2141. 5. FitzGerald JM, Bleecker ER, Bourdin A, et al. Two-year integrated efficacy and safety analysis of benralizumab SIROCCO, CALIMA, ZONDA, and BORA trials in severe asthma. Presented at: the American Thoracic Society (ATS) International Conference; May 17-22, 2019; Dallas, TX. 6. Busse WW, Bleecker ER, FitzGerald JM, et al. 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;7:46-59. 7. Data on File, REF-19697, AZPLP. 8. Data on File, REF-59636, AZPLP. 9. O’Quinn S, Xu X, Hirsch I. Rescue medication use reduction with benralizumab for patients with severe, uncontrolled eosinophilic asthma. Ann Allergy Asthma Immunol. 2018;121:S18-S21. 10. Bleecker ER, Wechsler M, FitzGerald JM, et al. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018;52:1800936. 11. Bleecker ER, FitzGerald JM, Chanez P, et al. Appendix to: 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;388:2115-2127. 12. FitzGerald JM, Bleecker ER, Nair P, et al. Appendix to: 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;388:2128-2141. 13. Data on File, REF-19698, AZPLP. 14. Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448-2458. 15. Nair P, Wenzel S, Rabe KF, et al. Supplementary Appendix to: Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448-2458.

References: 1. Data on File, REF-60828, AZPLP. 2. FASENRA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; October 2019. 3. Bleecker ER, FitzGerald JM, Chanez P, et al. 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;388:2115-2127. 4. FitzGerald JM, Bleecker ER, Nair P, et al. 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;388:2128-2141. 5. FitzGerald JM, Bleecker ER, Bourdin A, et al. Two-year integrated efficacy and safety analysis of benralizumab SIROCCO, CALIMA, ZONDA, and BORA trials in severe asthma. Presented at: the American Thoracic Society (ATS) International Conference; May 17-22, 2019; Dallas, TX. 6. Busse WW, Bleecker ER, FitzGerald JM, et al. 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;7:46-59. 7. Data on File, REF-19697, AZPLP. 8. Data on File, REF-59636, AZPLP. 9. O’Quinn S, Xu X, Hirsch I. Rescue medication use reduction with benralizumab for patients with severe, uncontrolled eosinophilic asthma. Ann Allergy Asthma Immunol. 2018;121:S18-S21. 10. Bleecker ER, Wechsler M, FitzGerald JM, et al. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018;52:1800936. 11. Bleecker ER, FitzGerald JM, Chanez P, et al. Appendix to: 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;388:2115-2127. 12. FitzGerald JM, Bleecker ER, Nair P, et al. Appendix to: 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;388:2128-2141. 13. Data on File, REF-19698, AZPLP. 14. Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448-2458. 15. Nair P, Wenzel S, Rabe KF, et al. Supplementary Appendix to: Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448-2458.

References: 1. Data on File, REF-60828, AZPLP. 2. FASENRA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; October 2019. 3. Bleecker ER, FitzGerald JM, Chanez P, et al. 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;388:2115-2127. 4. FitzGerald JM, Bleecker ER, Nair P, et al. 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;388:2128-2141. 5. FitzGerald JM, Bleecker ER, Bourdin A, et al. Two-year integrated efficacy and safety analysis of benralizumab SIROCCO, CALIMA, ZONDA, and BORA trials in severe asthma. Presented at: the American Thoracic Society (ATS) International Conference; May 17-22, 2019; Dallas, TX. 6. Busse WW, Bleecker ER, FitzGerald JM, et al. 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;7:46-59. 7. Data on File, REF-19697, AZPLP. 8. Data on File, REF-59636, AZPLP. 9. O’Quinn S, Xu X, Hirsch I. Rescue medication use reduction with benralizumab for patients with severe, uncontrolled eosinophilic asthma. Ann Allergy Asthma Immunol. 2018;121:S18-S21. 10. Bleecker ER, Wechsler M, FitzGerald JM, et al. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018;52:1800936. 11. Bleecker ER, FitzGerald JM, Chanez P, et al. Appendix to: 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;388:2115-2127. 12. FitzGerald JM, Bleecker ER, Nair P, et al. Appendix to: 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;388:2128-2141. 13. Data on File, REF-19698, AZPLP. 14. Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448-2458. 15. Nair P, Wenzel S, Rabe KF, et al. Supplementary Appendix to: Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448-2458.

References: 1. FASENRA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; November 2017. 2. Bleecker ER, FitzGerald JM, Chanez P, et al. 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;388:2115-2127. 3. FitzGerald JM, Bleecker ER, Nair P, et al. 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;388:2128-2141. 4. FitzGerald JM, Bleecker ER, Menzies-Gow A, et al. Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies. Lancet Respir Med. 2018;6(1):56-64. 5. Bleecker ER, Wechsler M, FitzGerald JM, et al. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018;52:1800936. 6. Bleecker ER, FitzGerald JM, Chanez P, et al. Appendix to: 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;388:2115-2127. 7. FitzGerald JM, Bleecker ER, Nair P, et al. Appendix to: 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;388:2128-2141. 8. Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448-2458. 9. Nair P, Wenzel S, Rabe KF, et al. Supplementary Appendix to: Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448-2458. 10. FitzGerald JM, Bleecker ER, Bourdin A, et al. Two-year integrated efficacy and safety analysis of benralizumab SIROCCO, CALIMA, ZONDA, and BORA trials in severe asthma. Presented at: the American Thoracic Society (ATS) International Conference; May 17-22, 2019; Dallas, TX. 11. Busse WW, Bleecker ER, FitzGerald JM, et al. 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;7:46-59. 12. Data on File, REF-19697, AZPLP. 13. O’Quinn S, Xu X, Hirsch I. Rescue medication use reduction with benralizumab for patients with severe, uncontrolled eosinophilic asthma. Ann Allergy Asthma Immunol. 2018;121:S18-S21. 14. Data on File, REF-52421, AZPLP.

References: 1. FASENRA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; October 2019. 2. Nucala [package insert]. Research Triangle Park, NC: GlaxoSmithKline LLC; September 2019. 3. Xolair [package insert]. South San Francisco, CA: Genentech Inc; May 2019. 4. Dupixent [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc. and sanofi-aventis U.S. LLC; June 2019. 5. Barker P, Ferguson GT, Cole J, et al. Single-use autoinjector functionality and reliability for at-home benralizumab administration: GRECO trial results. Presented at: the American Academy of Allergy, Asthma and Immunology (AAAAI) Congress; February 22-25, 2019; San Francisco, CA. Poster P289.

References: 1. FASENRA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; October 2019. 2. Busse WW, Bleecker ER, FitzGerald JM, et al. 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;7:46-59.