FASENRA STUDIES
FASENRA Pivotal Phase 3 Trials
SIROCCO and CALIMA were 2 pivotal Phase 3, randomized, double-blind, parallel-group, placebo-controlled, multicenter studies evaluating the impact of FASENRA across different populations of patients aged 12-75 years with severe eosinophilic asthma.1-3
- 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
Lung Function Results1-5
- In SIROCCO (48 weeks), significant improvement in FEV1: 398 mL with FASENRA + SOC (n=264) compared to 239 mL with placebo + SOC (n=261) (P=0.0006)*
- At Week 4, improvement in FEV1 was 290 mL with FASENRA + SOC (n=251) compared to 209 mL with placebo + SOC (n=249)
- In CALIMA (56 weeks), significant improvement in FEV1: 330 mL with FASENRA + SOC (n=238) compared to 215 mL with placebo + SOC (n=244), showing a 19% improvement from mean baseline FEV1 of 1.76 L (P=0.010)*
- At Week 4, improvement in FEV1 was 280 mL with FASENRA + SOC (n=232) compared to 152 mL with placebo + SOC (n=236)
*Pooled analysis of adult (treated with high-dose ICS/
LABA) and adolescent (treated with medium- to high-dose ICS/LABA) patients with severe asthma and baseline blood eosinophil count ≥300 cells/μL in SIROCCO and CALIMA randomized to treatment with FASENRA 30 mg SC Q8W.4
Patients with severe eosinophilic asthma with PAO
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Study design1-3,6
SIROCCO and CALIMA were randomized, double-blind, placebo-controlled, multicenter, Phase 3 pivotal studies in patients (12-75 years) with severe, uncontrolled asthma comparing FASENRA 30 mg SC Q4W for the first 3 doses, then Q8W thereafter; FASENRA 30 mg SC Q4W; and placebo SC.
A post-hoc analysis of pooled Phase 3 SIROCCO and CALIMA data was conducted in patients with severe, uncontrolled asthma who were receiving high-dose ICS/LABA and had baseline blood eosinophil counts of ≥300 cells/μL to evaluate PAO* influence on FASENRA treatment response.
- PAO+ defined as ratio (x100) of postbronchodilator FEV1 to FVC of less than 70%
- PAO- defined as ratio (x100) of postbronchodilator FEV1 to FVC of at least 70%
Inclusion Criteria1-3,6
- Baseline blood eosinophil level: ≥300 cells/μL
- 12-75 years of age with weight ≥40 kg
- Physician-diagnosed asthma requiring medium- to high-dose ICS/LABA for ≥12 months before enrollment
- ≥2 asthma exacerbations within 12 months before enrollment that required systemic corticosteroid therapy or temporary increase in usual maintenance OCS dosage
- Documented treatment with high-dose ICS/LABA† with or without OCS and additional asthma controllers for ≥3 months before enrollment
Primary Endpoint1,7
- Annual asthma exacerbation‡ rate (AER)1,7
Select Secondary Endpoints2,3
- Annual rate of exacerbations associated with ED visits or hospitalizations2,3
- Changes from baseline at EOT for prebronchodilator and postbronchodilator FEV12,3
While 2 dosing regimens were studied in SIROCCO, CALIMA, and ZONDA, the recommended dosing regimen is 30 mg of FASENRA administered every 4 weeks for the first 3 doses, then every 8 weeks thereafter.1
PAO in asthma can occur due to airway remodeling driven by continual inflammation, resulting in airflow limitation and lung function decline. While there is no standard definition, a postbronchodilator FEV1/FVC rate of <70% is the most common definition of PAO.6,8,9
*PAO may be used as an alternative term for fixed airflow obstruction. Asthma with PAO is considered its own clinical phenotype and is characterized by airflow obstruction that is persistent or incompletely reversible.9
†Fluticasone >500 µg/day or equivalent total daily dose.6
‡Exacerbation defined as worsening§ of asthma that led to 1 of the following: 1) use of systemic corticosteroids (or temporary increase in a stable background OCS dosage) for at least 3 days or a single depo-injectable dose of corticosteroids; 2) asthma-related emergency department/urgent care visit (<24 hours) that required systemic corticosteroids; or 3) asthma-related inpatient hospitalization (≥24 hours).2,3,7
§Worsening of asthma defined as any new or increased symptoms or signs that were concerning to the patient or related to an Asthma Daily Diary alert.2,3,7
Patient population in the post hoc analysis6
- Of 1493 total patients enrolled in SIROCCO and CALIMA, 63% (n=935; 308 placebo, 314 FASENRA Q4W, 313 FASENRA Q8W) were categorized as PAO+ and 37% (n=558; 193 placebo, 189 FASENRA Q4W, 176 FASENRA Q8W) as PAO-
- PAO+ patients were older, had asthma for a longer period, and were more likely to be former smokers than PAO- patients
- Baseline lung function was worse for PAO+ patients than for PAO- patients, and a greater percentage of PAO+ patients required OCS at study entry compared with PAO- patients
- The percentage reversibility ranges for PAO+ and PAO- patients overlapped substantially
Study Results
Post hoc pooled SIROCCO/
CALIMA: Annualized asthma exacerbation rate data by PAO status*6
Results are descriptive only.
Change measured from baseline in patients with PAO on FASENRA (n=313) and placebo (n=308), and in patients without PAO on FASENRA (n=176) and placebo (n=193). Patients were receiving high-dose ICS/LABA and had a baseline eosinophil count ≥300 cell/µL.6
* Based on a pooled post hoc analysis from the ITT population from SIROCCO and CALIMA in patients with severe eosinophilic asthma on high-dose ICS/LABA. Persistent airflow obstruction was defined as a ratio (x100) of post-bronchodilator FEV1/FVC <70% and non-persistent airflow obstruction defined as ≥70% at baseline.6
† Estimates calculated via a negative binomial model, with adjustment for study code, treatment, baseline value, region, OCS use at time of randomization, visit, and visit x treatment.6
Post hoc pooled SIROCCO/
CALIMA: Annual asthma exacerbation rate associated with ED visits or hospitalizations by PAO status*6
Results are descriptive only.
Data are from a pooled post hoc analysis of patients (aged 12-75 years) with high-dosage ICS/LABA and baseline blood eosinophil counts ≥300 cells/μL from the SIROCCO and CALIMA studies.*6
* Based on a pooled post hoc analysis from the ITT population from SIROCCO and CALIMA in patients with severe eosinophilic asthma on high-dose ICS/
LABA with baseline bEOS ≥300 cells/μL. Persistent airflow obstruction was defined as a ratio (x100) of post-bronchodilator FEV1/FVC <70% and non-persistent airflow obstruction defined as ≥70% at baseline.6
† Estimates were calculated via a negative binomial model, with adjustment for study code, treatment, baseline value, region, OCS use at time of randomization, visit, and visit x treatment.6
Post hoc pooled SIROCCO/
CALIMA: Lung function change by PAO status*6
Results are descriptive only.
Data are from a pooled post hoc analysis of patients (aged 12-75 years) with high-dosage ICS/LABA and baseline blood eosinophil counts ≥300 cells/μL from the SIROCCO and CALIMA studies.*6
* Based on a pooled post hoc analysis from the ITT population from SIROCCO and CALIMA in patients with severe eosinophilic asthma on high-dose ICS/LABA with baseline bEOS ≥300 cells/μL. Persistent airflow obstruction was defined as a ratio (x100) of post-bronchodilator FEV1/FVC <70% and non-persistent airflow obstruction defined as ≥70% at baseline.6
† Estimates were calculated via a negative binomial model, with adjustment for study code, treatment, baseline value, region, OCS use at time of randomization, visit, and visit x treatment.6
Post Hoc Analysis Limitations
Pooled analyses were not part of the general testing strategy, therefore all comparator results of FASENRA vs placebo are descriptive only. Classification of PAO was based on single test at randomization; however, the use of maximal bronchodilation procedure may help mitigate the influence of individual variability.6
Oral corticosteroid utilization data
Review resultsResources
Pivotal Study 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
AAER, annualized asthma exacerbation rate; bEOS, blood eosinophil; ED, emergency department; EOT, end of treatment; FAO, fixed airflow obstruction; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroid; ITT, intent-to-treat; LABA, long-acting beta-agonist; OCS, oral corticosteroid; PAO, persistent airflow obstruction; Q4W, every 4 weeks; Q8W, every 8 weeks; 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. 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. 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. 5. Data on File, REF-19697, AZPLP. 6. Chipps BE, Hirsch I, Trudo F, Alacqua M, Zangrilli JG. Benralizumab efficacy for patients with fixed airflow obstruction and severe, uncontrolled eosinophilic asthma. Ann Allergy Asthma Immunol. 2020;124(1):79-86. 7. 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. 8. 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. 9. 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.
