FASENRA STUDIES
Severe Eosinophilic Asthma (SEA)
FASENRA Pivotal Phase 3 Trials
In the 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 In the 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
In the ZONDA trial (28 weeks), a 75% median reduction in 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).1,4
See study designs below.
Patients with severe eosinophilic asthma with PAO
Exacerbation and real-world clinical data
Resources
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
ZONDA (Trial 3)4
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.4
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.4
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. 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.
