FASENRA STUDIES
FASENRA Pivotal Phase 3 Trial
- ZONDA trial (28 weeks): a 75% reduction in median final OCS dose was observed in OCS-dependent patients treated with FASENRA + SOC (n=73), compared to a 25% reduction with placebo + SOC (n=75) while maintaining asthma control (P<0.001)1,2
- ZONDA was a pivotal 28-week, randomized, double-blind, parallel-group, placebo-controlled, multicenter OCS-reduction study designed to evaluate the efficacy and safety of FASENRA in patients aged 18-75 years with OCS-dependent severe eosinophilic asthma. In ZONDA, OCS-dependent patients received chronic OCS therapy (7.5 to 40 mg daily) for 6 continuous months directly preceding enrollment1-3
Oral Corticosteroid Utilization
Collapse All
Study design4
PONENTE was a Phase 3b, open-label, single-arm, multicenter, OCS-reduction study designed to evaluate the efficacy and safety of tapering chronic OCS use in patients with uncontrolled severe eosinophilic asthma after initiation of FASENRA in patients aged ≥18 years.4
Primary endpoints were the proportion of patients4:
- Eliminating daily OCS, sustained for at least 4 weeks4
- Achieving elimination or a daily prednisone or prednisolone dosage of ≤5 mg, for at least 4 weeks, if further reduction was not possible because of adrenal insufficiency4
Results are descriptive only; no formal hypotheses were tested. PONENTE was an open-label, single-arm study.4
Study Limitations
The study evaluated FASENRA's treatment effect using an open-label, single-arm study design and did not include a control group to adjust for potential changes not due to treatment. Patients did not undergo an oral corticosteroid dosage-optimization phase and prednisolone levels were only assessed at baseline in patients who switched from another oral corticosteroid and were not assessed during the study
duration. This study was conducted in an adult population and the results cannot be extrapolated to children and
adolescents. Observed results are descriptive only; no formal hypotheses were tested. PONENTE was an open-label, single-arm study.4
*Guided by schema of OCS reduction defined in the study protocol.4,5
†EOT will vary from 44 to 68 weeks, depending on patient’s baseline OCS dose and other factors.4,5
Patient population4
Patients ≥18 years of age with a history of severe eosinophilic asthma on high-dose ICS/LABA ≥6 months with OCS ≥5 mg prednisone or equivalent for ≥3
months were enrolled. Blood EOS counts were ≥150 cells/μL at baseline or ≥300 cells/μL for ≤12 months (N=598).4
84% of patients had ≥1 exacerbation in prior 12 months.4
Baseline OCS Dosages:
- 5 mg/day (32%); >5 to ≤10 mg/day (43%); >10 mg/day (25%)4
OCS taper protocol4
Baseline dosage of OCS was 5 mg/day (32%); >5 to ≤10 mg/day (43%); >10 mg/day (25%).4
OCS dosage-reduction scheme to a daily dosage of 5 mg4
Note: Dosage reductions were allowed following an exacerbation, but at a slower pace; reductions were stopped if patients experienced 2 exacerbations. An exacerbation was defined as a worsening of asthma symptoms that led to the temporary need for systemic corticosteroids, emergency department or urgent care visit because of asthma that required a systemic corticosteroid bolus, or inpatient hospitalization related to asthma.4
Study Results
Change in OCS dose4,5
Results are descriptive only.
*Sustained over at least 4 weeks without worsening of asthma.4,5
†If reason for no further reduction was AI.4,5
‡0.0 mg (range, 0.0 to 40.0).4,5
Change in exacerbations4,5
Results are descriptive only.
*Compared to 16% in the year prior to enrollment.4,5
†563 patients completed the reduction phase and entered the maintenance phase.4,5
Do not abruptly discontinue corticosteroids. Dose reductions, if appropriate, should be gradual and may be associated with withdrawal symptoms and/or unmask previously controlled conditions.
Percent of systemic corticosteroid dependency stratified by eosinophil counts6,7
Results are descriptive only.
Change measured from baseline (pre-index) in OCS-dependent patients stratified by BEC.6,7
Study Limitations
Data are observational in nature. Clinical implications cannot be determined.
Do not abruptly discontinue corticosteroids. Dose reductions, if appropriate, should be gradual and may be associated with withdrawal symptoms and/or unmask previously controlled symptoms.
Percent of systemic corticosteroid dependency8
Results are descriptive only.
Change measured from baseline (pre-index) in patients using maintenance OCS (n=204).8
In ZEPHYR 1, OCS dependence was defined during the 12-month period in 2 ways: (i) a cumulative dose of at least 450 mg prednisone equivalent of OCS over 90 consecutive days, or (ii) at least 180 days of supply of OCS.8
Study Limitations
Data are observational in nature. Clinical implications cannot be determined.
Do not abruptly discontinue corticosteroids. Dose reductions, if appropriate, should be gradual and may be associated with withdrawal symptoms and/or unmask previously controlled symptoms.
MELTEMI: 5-year safety and
efficacy data
Resources
Study Designs
ZONDA (Trial 3)2
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; FASENRA 30 mg SC Q4W; and placebo SC Q4W. A total of 220 adult patients aged 18 to 75 years with severe asthma on high-dose ICS/LABA and daily OCS (7.5 to 40 mg/day), a blood eosinophil count 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.2
In ZONDA, asthma exacerbation was defined as a worsening of asthma that led to a temporary increase in systemic corticosteroid dose for at least 3 days to treat the symptoms, an ED visit resulting from asthma that led to treatment with a systemic corticosteroid in addition to the patient’s regular maintenance medications, or inpatient hospitalization because of asthma.2
PONENTE (Phase 3b Oral Corticosteroid Reduction Trial)4,5
An open-label, single-arm, multicenter, Phase 3b OCS-reduction study designed to evaluate the efficacy and safety of tapering chronic OCS use in patients with uncontrolled severe eosinophilic asthma after initiation of FASENRA. Patients received FASENRA 30 mg SC Q4W for the first 3 doses, then Q8W thereafter. The benralizumab treatment period consisted of a 4-week induction phase with no OCS adjustments, followed by a variable, personalized OCS reduction phase, and a 24-32 week maintenance phase. A total of 598 adult (≥18 years old) patients on high-dose ICS plus LABA for ≥6 months and daily OCS (≥5 mg) for ≥3 months were included. Patients had a bEOS count of ≥150 cells/μL at baseline or ≥300 cells/μL in the previous 12 months for inclusion in the study. The primary endpoints were percentage of patients who achieved a 100% reduction in daily OCS dosage and percentage of patients who achieved a 100% dosage reduction or achieved a daily OCS dosage ≤5 mg if further reduction was not possible because of adrenal insufficiency. After the OCS reduction phase, patients spent approximately 6 months in the maintenance phase. During this time, they continued treatment with 30 mg benralizumab Q8W and either continued without OCS treatment or continued with the final dosage they had achieved in the reduction phase. Investigators could prescribe corticosteroids for exacerbations or increase daily dose in cases of decreased asthma control.4,5
In PONENTE, FASENRA was administered in addition to daily OCS (≥5 mg) plus SOC, which is defined as high-dose ICS plus LABA.4,5
ZEPHYR 18
ZEPHYR 1 was a retrospective cohort study of patients aged 12 years or older initiating FASENRA between November 2017 and November 2018 using data between 2016 and 2019 from a large US payer dataset. A pre-post design was implemented to descriptively analyze and compare asthma exacerbations between the 12-month pre-index and 12-month post-index periods. Asthma exacerbations were defined based on a combination of asthma exacerbation diagnosis codes in the inpatient, emergency, and outpatient settings along with records for systemic corticosteroid use.8
Eligible patients initiating FASENRA (n=912) were diagnosed with asthma, aged ≥12 years at index, had at least 2 records of benralizumab, and had 24 months of continuous insurance enrollment. The primary cohort (n=204) included patients who were biologic-naive and had at least 2 asthma exacerbations during the 12 months pre-index. The secondary cohort (n=103) examined persistent FASENRA users (≥6 records of FASENRA). Additional cohorts included patients who switched to FASENRA from omalizumab (n=114) or mepolizumab (n=97) with no requirement for an exacerbation history during the pre-index period.8
ZEPHYR 1 STUDY LIMITATIONS8
- The study evaluated the treatment effect of FASENRA using a pre-post study design and did not include a control arm to adjust for potential temporal changes not due to treatment8
- It is possible that some patients received their first FASENRA dose as a free dose that was not visible in the payer data8
- The exact reasons behind a patient’s switch from one medication to another cannot be ascertained from the data8
This is an observational study; clinical implications cannot be determined from this payer database study.
ZEPHYR 27,10
ZEPHYR 2 was a retrospective cohort study of patients 12 years or older initiating FASENRA between November 2017 and June 2019 using data between 2016 and 2020 from a large US payer dataset. A pre-post design was implemented to descriptively analyze and compare asthma exacerbations, OCS use, and other outcomes between the 12-month pre-index and 12-month post-index periods. An additional cohort examined asthma exacerbations 12-18 or 24 months post-index. Asthma exacerbations were defined based on a combination of asthma exacerbation diagnosis codes in the inpatient, emergency, and outpatient settings along with records for systemic corticosteroid use.7,10
Eligible patients initiating FASENRA (N=8473) were diagnosed with asthma, aged ≥12 years at index, had 24 months of continuous insurance enrollment, and had ≥2 asthma exacerbations in the pre-index period. The primary cohort (n=1292) was biologically naive and focused on patients with ≥2 records of FASENRA. Subgroups included patients who switched to FASENRA from omalizumab (n=205) or mepolizumab (n=144), and a cohort stratified by blood eosinophil level (n=429). The long-term follow-up cohort included patients with ≥18 months of follow-up data who had ≥9 records of FASENRA (n=419) and patients with ≥24 months of follow-up data who had ≥11 records of FASENRA (n=156).7,10
ZEPHYR 2 STUDY LIMITATIONS7,10
- The study evaluated the treatment effect of FASENRA using a pre-post study design and did not include a control arm to adjust for potential temporal changes not due to treatment7,10
- It is possible that some patients received their first FASENRA dose as a free dose that was not visible in the payer data7,10
- The exact reasons behind a patient’s switch from one medication to another cannot be ascertained from the data7,10
This is an observational study; clinical implications cannot be determined from this payer database study.
AI, adrenal insufficiency; BEC, blood eosinophil count; bEOS, blood eosinophil; ED, emergency department; EOT, end of treatment; HD-ICS, high-dose inhaled corticosteroid; HRU, healthcare resource utilization; ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; OCS, oral corticosteroid; PAO, persistent airflow obstruction; Q1W, every week; Q2W, every 2 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks; RWE, real-world evidence; SC, subcutaneous; SOC, standard of care.
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
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.
References:
1. FASENRA® (benralizumab) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; September 2026. 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. Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376(25)(suppl):2448-2458. 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 [published correction appears in Lancet Respir Med. 2021;9(12):e114]. 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. 6. Maselli DJ, Carstens D, Yang D, et al. Benralizumab is effective in reducing asthma exacerbations: results from the ZEPHYR 2 Study. Presented at: American College of Allergy, Asthma & Immunology Annual Scientific Meeting; November 4–8, 2021; New Orleans, LA. 7. 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. 8. Chung Y, Katial R, Mu F, et al. Real-world effectiveness of benralizumab: results from the ZEPHYR 1 study. Ann Allergy Asthma Immunol. 2022;128(6):669-676.e6. 9. Adrish M. Reduction in asthma exacerbations following initiation of benralizumab among Medicare beneficiaries: results from the ZEPHYR-5 study. Presented at: American Academy of Allergy, Asthma & Immunology (AAAAI)/World Allergy Organization (WAO) 2025; February 28–March 3, 2025; San Diego, CA. 10. Chung Y, Maselli DJ, Mu F, et al. Impact of benralizumab on asthma exacerbation-related medical healthcare resource utilization and medical costs: results from the ZEPHYR 2 study. J Med Econ. 2023;26(1):954-962.
