FASENRA is indicated for the add-on maintenance treatment of patients 12 years and older and with severe eosinophilic asthma. FASENRA is not indicated for treatment of other eosinophilic conditions, relief of acute bronchospasm or status asthmaticus.

FASENRA is indicated for the add-on maintenance treatment of patients 12 years and older and with severe eosinophilic asthma. FASENRA is not indicated for treatment of other eosinophilic conditions, relief of acute bronchospasm or status asthmaticus.

POWER TO PREVENT

EXACERBATIONS

WITH BETTER BREATHING AFTER THE FIRST DOSE1-4*

FASENRA is proven to reduce annual exacerbation rate and improve lung function in patients with severe eosinophilic asthma. Improvements in lung function were observed as early as week 4.1-4*

*Statistical significance for FEV1 improvement was established at end of treatment. Week 4 results were descriptive only. FASENRA demonstrated greater improvements in change from baseline in pre-bronchodilator FEV1 compared with placebo at Week 4 (first measured time point after administration of treatment dose) that were maintained through end of treatment.2-4

*Statistical significance for FEV1 improvement was established at end of treatment. Week 4 results were descriptive only. FASENRA demonstrated greater improvements in change from baseline in pre-bronchodilator FEV1 compared with placebo at Week 4 (first measured time point after administration of treatment dose) that were maintained through end of treatment.2-4

STUDY DESIGNS

TRIAL 1 - SIROCCO AND TRIAL 2 - CALIMA2,3

Trial 1 (48-week) and Trial 2 (56-week) 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 (Trial 1) and 1306 (Trial 2) patients aged 12-75 years old with severe asthma uncontrolled on high-dose ICS (Trial 1) and medium- to high-dose ICS (Trial 2) 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 blood eosinophil counts (≥300 cells/μL and <300 cells/μL).The primary endpoint was annual exacerbation rate ratio versus placebo in patients with blood eosinophil 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 pre-bronchodilator FEV1 and total asthma symptom score at Week 48 (Trial 1) and Week 56 (Trial 2) in the same population.

TRIAL 3 - ZONDA5

A 28-week, randomized, double-blind, parallel-group, placebo-controlled, multicenter OCS reduction study comparing the efficacy and safety of FASENRA (30 mg SC) Q4W for the first 3 doses, then Q8W thereafter; benralizumab (30 mg SC) Q4W, and placebo (SC) Q4W. A total of 220 adult (18-75 years old) patients with severe asthma on high-dose ICS plus LABA and chronic OCS (7.5 to 40 mg/day), blood eosinophil counts of ≥150 cells/μL, and a history of ≥1 exacerbation in the previous year were included. The primary endpoint was the median percent reduction from baseline in the final daily OCS dose while maintaining asthma control.

PHASE II STUDY6

A 12-week, Phase II, randomized, double-blind, placebo-controlled, dose-increase study benralizumab in adults with mild to moderate asthma. Patients were randomized to receive SC administration of benralizumab 25 mg (n=6), benralizumab 100 mg (n=6), benralizumab 200 mg (n=6), or placebo (n=6) Q4W for a total of 3 doses. One objective was to assess the effect of benralizumab on blood eosinophil counts and protein biomarkers. Median blood eosinophil levels at baseline were 400, 200, 120, and 200 cells/μL in the 25, 100, and 200 mg benralizumab and placebo groups, respectively.

STUDY DESIGNS

TRIAL 1 - SIROCCO AND TRIAL 2 - CALIMA2,3

Trial 1 (48-week) and Trial 2 (56-week) 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 (Trial 1) and 1306 (Trial 2) patients aged 12-75 years old with severe asthma uncontrolled on high-dose ICS (Trial 1) and medium- to high-dose ICS (Trial 2) 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 blood eosinophil counts (≥300 cells/μL and <300 cells/μL).The primary endpoint was annual exacerbation rate ratio versus placebo in patients with blood eosinophil 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 pre-bronchodilator FEV1 and total asthma symptom score at Week 48 (Trial 1) and Week 56 (Trial 2) in the same population.

TRIAL 3 - ZONDA5

A 28-week, randomized, double-blind, parallel-group, placebo-controlled, multicenter OCS reduction study comparing the efficacy and safety of FASENRA (30 mg SC) Q4W for the first 3 doses, then Q8W thereafter; benralizumab (30 mg SC) Q4W, and placebo (SC) Q4W. A total of 220 adult (18-75 years old) patients with severe asthma on high-dose ICS plus LABA and chronic OCS (7.5 to 40 mg/day), blood eosinophil counts of ≥150 cells/μL, and a history of ≥1 exacerbation in the previous year were included. The primary endpoint was the median percent reduction from baseline in the final daily OCS dose while maintaining asthma control.

PHASE II STUDY6

A 12-week, Phase II, randomized, double-blind, placebo-controlled, dose-increase study benralizumab in adults with mild to moderate asthma. Patients were randomized to receive SC administration of benralizumab 25 mg (n=6), benralizumab 100 mg (n=6), benralizumab 200 mg (n=6), or placebo (n=6) Q4W for a total of 3 doses. One objective was to assess the effect of benralizumab on blood eosinophil counts and protein biomarkers. Median blood eosinophil levels at baseline were 400, 200, 120, and 200 cells/μL in the 25, 100, and 200 mg benralizumab and placebo groups, respectively.

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%) 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

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.

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

*Pharyngitis was defined as follows: pharyngitis, pharyngitis bacterial, viral pharyngitis, and pharyngitis streptococcal.

Hypersensitivity reactions were defined as follows: urticaria, urticaria papular, and rash.

Adverse reactions from Trial 3 ZONDA with 28 weeks of treatment with FASENRA (n=73) or placebo (n=75) in which the incidence was more common in FASENRA than placebo include headache (8.2% compared to 5.3%, respectively) and pyrexia (2.7% compared to 1.3%, respectively). The frequencies for the remaining adverse reactions with FASENRA were similar to placebo.1

Overall, treatment-emergent anti-drug antibody response developed in 13% of patients treated with FASENRA at the recommended dosing regimen during the 48- to 56-week treatment period. A total of 12% of patients treated with FASENRA developed neutralizing antibodies. Anti-benralizumab antibodies were associated with increased clearance of benralizumab and increased blood eosinophil levels in patients with high anti-drug antibody titers compared to antibody negative patients. No evidence of an association of anti-drug antibodies with efficacy or safety was observed.1

Please read full Prescribing Information and Patient Information

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

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 β2-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. Data on File, REF-19697, AZPLP.

5. 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.

6. Pham TH, Damera G, Newbold P, Ranade K. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016;111:21-29.

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.

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%) 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

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.

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

*Pharyngitis was defined as follows: pharyngitis, pharyngitis bacterial, viral pharyngitis, and pharyngitis streptococcal.

Hypersensitivity reactions were defined as follows: urticaria, urticaria papular, and rash.

Adverse reactions from Trial 3 ZONDA with 28 weeks of treatment with FASENRA (n=73) or placebo (n=75) in which the incidence was more common in FASENRA than placebo include headache (8.2% compared to 5.3%, respectively) and pyrexia (2.7% compared to 1.3%, respectively). The frequencies for the remaining adverse reactions with FASENRA were similar to placebo.1

Overall, treatment-emergent anti-drug antibody response developed in 13% of patients treated with FASENRA at the recommended dosing regimen during the 48- to 56-week treatment period. A total of 12% of patients treated with FASENRA developed neutralizing antibodies. Anti-benralizumab antibodies were associated with increased clearance of benralizumab and increased blood eosinophil levels in patients with high anti-drug antibody titers compared to antibody negative patients. No evidence of an association of anti-drug antibodies with efficacy or safety was observed.1

Please read full Prescribing Information and Patient Information

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

 

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