FASENRA STUDIES
FASENRA Pivotal Phase 3 Trials
- SIROCCO trial (48 weeks): 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)1,2
- CALIMA trial (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
Real-World Data
The ZEPHYR Program included several large RWE claims database studies of retrospective, observational, pre-post cohort design to evaluate the impact of FASENRA on clinical and economic outcomes in patients aged ≥12 years with severe eosinophilic asthma, including the impact of asthma exacerbations and related HRU, OCS use, and medical costs.4-7
These are observational studies; therefore, clinical implications cannot be determined from these claims database studies. Data are descriptive only.4-6
Collapse all -
Study design5,8
A pre-post design was used to analyze and compare asthma exacerbations 12 months before and after FASENRA treatment initiation.5,8
The objectives of the study5,8:
- Evaluate the change in asthma exacerbations following initiation of FASENRA among older patients5,8
- Examine the relationship between FASENRA adherence, asthma exacerbations, and costs among patients with a diagnosis of severe eosinophilic asthma newly initiating FASENRA5,8
Study Limitations
The study evaluated FASENRA’s treatment effect using a pre-post study design and did not include a control arm to adjust for potential temporal changes not due to treatment. It is possible that some patients received their first FASENRA dose as a free dose that was not visible in the claims data. This is an observational study; therefore, clinical implications cannot be determined.5
Patient flow5
A pre-post design was used to analyze and compare asthma exacerbations 12 months before and after FASENRA treatment initiation.5
7706 adult patients evaluated in ZEPHYR 5 study.
- 4611 patients on Medicare (MA and MFFS) were included to evaluate the change in asthma exacerbations following initiation of FASENRA among older patients
- In this cohort:
- The mean (SD) age was 69.3 (±10.9) years
- The majority of patients were women (n=3185; 69.1%)
Study Results5
Change in annual asthma exacerbation rate in Medicare patients5
Results are descriptive only.
Change in AAER measured from baseline (pre-index) in Medicare patients (N=4611).5
Percentage of Medicare patients who experienced 0, 1, 2, 3, and 4+ asthma exacerbations5
Results are descriptive only.
N=4611.
Respiratory medication utilization in Medicare patients receiving FASENRA5
Results are descriptive only.
N=4611.
Exacerbation-related healthcare utilization and costs in Medicare patients*5
Costs are presented among all patients in the sample, regardless of them experiencing an exacerbation. For patients with baseline hospital-based exacerbations, the mean inpatient cost was $10,673 ± $9,955.
Results are descriptive only.
N=4611.
*Exacerbation-related service utilization and costs were based on an asthma exacerbation. The following contributed to healthcare costs: physician office/clinic visit, emergency department, inpatient hospital costs, and outpatient costs.5
Impact of treatment adherence on asthma exacerbations8
Results are descriptive only.
Change in number of exacerbations measured from baseline (pre-index) in patients studied (N=7706).8
A total of 7706 patients with severe asthma were included in the analysis. 78.7% (n=6067) were classified as adherent to FASENRA and 21.3% (n=1639) were classified as non-adherent.8
Study design6,7
A pre-post design was used to analyze and compare asthma exacerbations 12 months before and after FASENRA treatment initiation.6,7
The objectives of the study6,7:
- To descriptively characterize patients who are treated with FASENRA, including those with up to 24 months of follow-up data available6,7
- To understand the long-term real-world impact of FASENRA treatment on asthma exacerbations, asthma exacerbation-related medical cost and HRU, and asthma medication use6,7
Primary Cohort:
The primary cohort (n=1292) was biologic-naive and focused on patients with ≥2 records of FASENRA.6
Study Limitations
The study evaluated FASENRA’s treatment effect using a pre-post study design and did not include a control arm to adjust for potential temporal changes not due to treatment. It is possible that some patients received their first FASENRA dose as a free dose that was not visible in the claims data. Data are observational in nature. Clinical implications cannot be determined. The exact reasons behind a patient’s transition from one medication to another cannot be ascertained from the data. The efficacy and safety of FASENRA have not been evaluated in head-to-head trials vs omalizumab or mepolizumab.6,7
Blood eosinophil level cohort7
*The record for FASENRA occurring the day before the index day is included in the count of FASENRA records.7
†All patients included in the final sample had at least 1 encounter record every 12 months in the pre- and post-index periods.7
Switch cohort7
*The record for FASENRA occurring the day before the index day is included in the count of FASENRA records.7
†All patients included in the final sample had at least 1 encounter record every 12 months in the pre- and post-index periods.7
Long-term follow-up cohort7
*The record for FASENRA occurring the day before the index day is included in the count of FASENRA records.7
†All patients included in the final sample had at least 1 medical and pharmacy claim in the 12 months in the pre- and post-index periods.7
Study Results
Impact of FASENRA on asthma exacerbation rate: cohort stratified by blood eosinophil level7
Results are descriptive only.
Change in AAER measured from baseline (pre-index) in patients studied (N=429).7
Asthma exacerbation rate over an 18-month and 24-month period7
Results are descriptive only.
*Change from pre-index period.7
Asthma exacerbation rate in biologic-experienced patients who transitioned to FASENRA7
Results are descriptive only.
Change measured from baseline (pre-index) in patients who transitioned from omalizumab to FASENRA (n=205) and patients who transitioned from mepolizumab to FASENRA (n=144).7
Study design4
A pre-post design was used to analyze and compare asthma exacerbations 12 months before and after FASENRA treatment initiation.4
The objectives of the study4:
- To descriptively characterize the population of patients treated with FASENRA in terms of patient demographics, comorbidities, and other asthma medications4
- To understand the benefit of FASENRA on asthma exacerbations4
Study Limitations
The study evaluated FASENRA’s treatment effect using a pre-post study design and did not include a control arm to adjust for potential temporal changes not due to treatment. It is possible that some patients received their first FASENRA dose as a free dose that was not visible in the claims data. Data are observational in nature. Clinical implications cannot be determined. The exact reasons behind a patient’s transition from one medication to another cannot be ascertained from the data. The efficacy and safety of FASENRA have not been evaluated in head-to-head trials vs omalizumab or mepolizumab.4
Patient flow4
A pre-post design was used to analyze and compare asthma exacerbations 12 months before and after FASENRA treatment initiation.4
*The record for FASENRA occurring the day before the index day is included in the count of FASENRA records.4
†Biologics included omalizumab, mepolizumab, reslizumab, and dupilumab.4
Study Results
Real-world asthma exacerbation rate data4,9
Results are descriptive only.
Change in AAER measured from baseline (pre-index) in the primary cohort (N=204) and the persistent group (N=103).4,9
Asthma exacerbation rate in biologic-experienced patients who transitioned to FASENRA4,9
Results are descriptive only.
Change in exacerbation rate compared to baseline (pre-index) in patients who transitioned from omalizumab (n=114) or mepolizumab (n=97) to FASENRA.4,9
Patients with severe eosinophilic asthma with PAO
Explore detailsResources
Learn moreStudy Designs
SIROCCO AND CALIMA (Trials 1 and 2)1-3
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 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 blood eosinophil counts (≥300 cells/μL and <300 cells/μL). The primary endpoint was annual exacerbation rate ratio vs placebo in patients with blood eosinophil counts of ≥300 cells/μL on high-dose ICS/LABA. Key secondary endpoints were prebronchodilator FEV1 and total asthma symptom score at Week 48 (SIROCCO) and Week 56 (CALIMA) in the same population.1-3
In SIROCCO (48 weeks) and CALIMA (56 weeks), asthma exacerbation was 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.1-3
ZEPHYR 55,8
ZEPHYR 5 was a retrospective, observational study of patients with severe eosinophilic asthma receiving FASENRA. The study used data from MFFS administrative claims database and MORE closed claims database (commercial, Medicare Advantage, Managed Medicaid claims). A pre-post design was implemented to descriptively analyze the adherence, asthma exacerbations, and costs among patients diagnosed with severe eosinophilic asthma. Eligible patients (N=7706) were enrolled in a health plan 12 months preceding and following index date, asthma diagnosis, and presence of ≥2 asthma exacerbations during baseline. Patients were classified as adherent vs non-adherent based on number of treatment claims during follow-up (≥6 vs <6 FASENRA claims). Asthma exacerbations were defined as an asthma-related hospitalization, outpatient asthma visit with filled prescription of OCS within 7 days, or treatment with mechanical ventilation. Data from 2017-2023 were used for the analyses.5,8
A subset of the above data (MFFS and Medicare Advantage claims) was utilized to evaluate the change in asthma exacerbations following initiation of FASENRA among Medicare patients. A pre-post design was implemented to evaluate asthma exacerbations between the 12-month pre-index (baseline) and 12-month post-index (follow-up) periods. Eligible patients (n=4611) were enrolled with MFFS or MA benefits 12 months preceding and following index date, had an asthma diagnosis, and presence of ≥2 asthma exacerbations during baseline. Asthma exacerbations were defined the same as presented above for the full-data analysis. Data from 2017-2023 were used for the analyses.5,8
ZEPHYR 5 STUDY LIMITATIONS5,8
- 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 treatment5,8
- It is possible that some patients received their first FASENRA dose as a free dose that was not visible in the payer data5,8
This is an observational study; clinical implications cannot be determined from this payer database study.
ZEPHYR 26,7
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.6,7
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).6,7
ZEPHYR 2 STUDY LIMITATIONS6,7
- 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 treatment6,7
- It is possible that some patients received their first FASENRA dose as a free dose that was not visible in the payer data6,7
- The exact reasons behind a patient’s switch from one medication to another cannot be ascertained from the data6,7
This is an observational study; clinical implications cannot be determined from this payer database study.
ZEPHYR 14
ZEPHYR 1 was a retrospective cohort study of patients 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.4
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.4
ZEPHYR 1 STUDY LIMITATIONS4
- 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 treatment4
- It is possible that some patients received their first FASENRA dose as a free dose that was not visible in the payer data4
- The exact reasons behind a patient’s switch from one medication to another cannot be ascertained from the data4
This is an observational study; clinical implications cannot be determined from this payer database study.
AAER, annual asthma exacerbation rate; FEV1, forced expiratory volume in 1 second; HRU, healthcare resource utilization; ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; LAMA, long-acting muscarinic agonist; MA, Medicare Advantage; MFFS, Medicare fee-for-service; OCS, oral corticosteroid; PAO, persistent airflow obstruction; Q4W, every 4 weeks; Q8W, every 8 weeks; RWE, real-world evidence; SABA, short-acting beta-agonist; SC, subcutaneous; SD, standard deviation; 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. 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. 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. 5. 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. 6. 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. 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. Adrish M, DeMartino JK, Carstens D, et al. Benralizumab adherence reduces exacerbations and exacerbation-related medical costs among patients with severe asthma: results from the ZEPHYR-5 study. Presented at: ATS 2025 International Conference, May 18–21, 2025; San Francisco, CA. 9. Carstens DD, Young J, Cook EE, et al. Real-world effectiveness of benralizumab on asthma exacerbations: results from the ZEPHYR 1 study. Presentation at: ATS 2021; Virtual May 14-19, 2021.
