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
- 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)1,4
Adverse Reactions
Most common adverse reactions (incidence greater than or equal to 5%) include headache and pharyngitis.*1 See full Important Safety Information below.
*Pharyngitis was defined as follows: pharyngitis, pharyngitis bacterial, viral pharyngitis, and pharyngitis streptococcal.1
MELTEMI: 5-Year Safety and Efficacy Data
MELTEMI was an open-label, Phase 3 safety extension study that enrolled patients who were previously enrolled in 1 of the 3 Phase 3 randomized, double-blind, placebo-controlled predecessor studies—SIROCCO, CALIMA, or ZONDA—and enrolled in BORA for ≥16 weeks and <40 weeks and then transitioned to MELTEMI (N=447). Patients were aged 18-75 years with severe eosinophilic asthma and were being treated with ICS/LABA therapy ± OCS and/or other asthma controllers.5
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Study design5
MELTEMI is a Phase 3, open-label, safety extension study in adults with severe eosinophilic asthma who completed one of three Phase 3, randomized, double-blind, placebo-controlled predecessor trials (SIROCCO, CALIMA, ZONDA), enrolled in the BORA extension trial, and transitioned to the MELTEMI open-label extension (N=447).5
Inclusion criteria5:
- Adults (aged 18-75 years) with uncontrolled severe eosinophilic asthma
- Completed one of the three Phase 3, randomized, double-blind, placebo-controlled predecessor studies
- Enrolled in the double-blind BORA extension study
Primary endpoint5:
Safety and tolerability measured by rates of AEs and SAEs
*Eligible patients transitioned from the predecessor study into BORA at the EOT visit of the predecessor study.5
†Includes patients who discontinued treatment in MELTEMI but attended all study visits.5
‡447 patients enrolled in MELTEMI; 1 patient did not receive treatment with study drug and was not included in the full analysis set.5
Study Limitations
There was no control arm, and there was potential selection bias. Patients who did not experience benefits with their asthma treatment may have been more likely to discontinue the study vs those who did experience benefits and, similarly, patients who experienced certain serious adverse events in predecessor studies were not eligible to enter MELTEMI, both of which could contribute to selection bias.5
Patient characteristics5
Patient characteristics (FASENRA, N=446)5
- ≥3 years mean on-treatment duration in each group5
- 157 (35.2%) patients received
treatment with FASENRA (Q4W or Q8W) for ≥4 years5 - ~16% of patients initiating FASENRA at baseline were on treatment for ≥5 years5
Anti-drug antibody prevalence was consistent with previous studies of FASENRA.5
5-year safety data across predecessor and extension studies5
- AEs and serious adverse events did not increase over time5
- Serious infection, hypersensitivity, immunogenicity, and malignancy rates were low and similar across all groups5
Predecessor Studies
(SIROCCO, CALIMA, ZONDA)5
Extension Studies*
(BORA, MELTEMI)5
| Parameter | ||||
|---|---|---|---|---|
| FASENRA Q8W (n=159) [Exp=146]† |
Placebo (n=137) [Exp=124]† |
FASENRA Q8W (n=159) [Exp=444]† |
PBO to FASENRA Q8W (n=67) [Exp=207]† |
|
| Any AE, n (ER) | 115 (78.7) | 111 (89.4) | 136 (30.7) | 59 (28.5) |
| Nasopharyngitis | 26 (17.8) | 27 (21.7) | 53 (11.9) | 25 (12.1) |
| Asthma | 15 (10.3) | 33 (26.6) | 33 (7.4) | 9 (4.3) |
| Bronchitis | 14 (9.6) | 24 (19.3) | 19 (4.3) | 13 (6.3) |
| Headache | 12 (8.2) | 9 (7.2) | 22 (5.0) | 8 (3.9) |
Predecessor Studies
(SIROCCO, CALIMA, ZONDA)5
| Parameter | FASENRA Q8W (n=159) [Exp=146]† |
Placebo (n=137) [Exp=124]† |
|---|---|---|
| Any AE, n (ER) | 115 (78.7) | 111 (89.4) |
| Nasopharyngitis | 26 (17.8) | 27 (21.7) |
| Asthma | 15 (10.3) | 33 (26.6) |
| Bronchitis | 14 (9.6) | 24 (19.3) |
| Headache | 12 (8.2) | 9 (7.2) |
Extension Studies*
(BORA, MELTEMI)5
| Parameter | FASENRA Q8W (n=159) [Exp=444]† |
PBO to FASENRA Q8W (n=67) [Exp=207]† |
|---|---|---|
| Any AE, n (ER) | 136 (30.7) | 59 (28.5) |
| Nasopharyngitis | 53 (11.9) | 25 (12.1) |
| Asthma | 33 (7.4) | 9 (4.3) |
| Bronchitis | 19 (4.3) | 13 (6.3) |
| Headache | 22 (5.0) | 8 (3.9) |
There were no new safety signals and no deaths in the on-treatment window.5
*Extension studies include time on treatment in the double-blind BORA extension as well as the open-label MELTEMI extension.5
†Total exposure in years across patients in
treatment group and study period.5
Proportion of patients with zero exacerbations5
Results are descriptive only.
Efficacy analysis includes patients with bEOS ≥300 cells/μL receiving HD-ICS at baseline. Of the patients receiving FASENRA Q8W, 59% had zero exacerbations across the extension study period (n=110; over 304 total follow-up years).5
Exacerbation rates in patients with baseline bEOS ≥300 cells/μL + HD-ICS5
Results are descriptive only.
In patients with baseline bEOS ≥300 cells/μL + HD-ICS per GINA guidelines (>500 μg fluticasone propionate equivalents daily).5
*Due to the open-label extension design in MELTEMI, there were differences in time on treatment with FASENRA. Study duration varied based on discontinuations and timing of commercial availability in various local markets.5
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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
BORA (Phase 3 Safety Extension Trial)6
A randomized, double-blind, parallel-group, Phase 3 extension study that enrolled patients who completed SIROCCO or CALIMA (n=1576). Patients enrolled in the previous studies were aged 12 to 75 years and had physician-diagnosed asthma requiring treatment with medium-dose or high-dose ICS/LABA for at least 12 months with or without additional controllers prior to enrollment. Patients originally randomized to FASENRA continued FASENRA 30 mg SC Q8W or FASENRA SC Q4W. Patients previously receiving placebo were rerandomized 1:1 to FASENRA 30 mg SC Q4W for the first 3 doses, then Q8W thereafter or FASENRA 30 mg SC Q4W except for adolescent patients in the EU who were randomized to FASENRA 30 mg SC Q8W. Patients were to be maintained on their same dose of ICS/LABA. End of treatment was at Week 56 for adults and Week 108 for adolescents. The primary objective was assessment of safety and tolerability. Secondary objectives included assessments of asthma exacerbations, prebronchodilator forced expiratory volume in 1 second (FEV1), and impact of treatment on blood eosinophil levels.6
MELTEMI (Phase 3 Safety Extension Trial)5
An open-label, Phase 3 extension study that enrolled patients who were previously enrolled in a predecessor clinical trial—SIROCCO, CALIMA, or ZONDA—and enrolled in BORA for ≥16 weeks and <40 weeks and then transitioned to MELTEMI. In predecessor studies, patients received placebo or FASENRA 30 mg SC, either Q4W or Q8W (first 3 doses Q4W); in BORA, patients receiving placebo were randomized to FASENRA Q4W or Q8W and continued on the same treatment in MELTEMI until FASENRA was commercially available in their local market. In MELTEMI, patients received either FASENRA 30 mg SC Q4W or FASENRA 30 mg SC Q8W. Patients enrolled in MELTEMI were aged 18 years or older, had a diagnosis of severe asthma, and were being treated with ICS/LABA therapy ± OCS and/or other asthma controllers. The primary endpoint was safety and tolerability measured by rates of AEs and SAEs. In MELTEMI, patients could continue in the study until FASENRA was commercially available in their local market or for 130 weeks in countries in which a marketing application was not submitted. As FASENRA became approved in various markets, patient numbers declined.5
Study limitations: There was no control arm, and there was potential selection bias. Patients who did not experience benefits with their asthma treatment may have been more likely to discontinue the study vs those who did experience benefits and, similarly, patients who experienced certain serious adverse events in predecessor studies were not eligible to enter MELTEMI, both of which could contribute to selection bias.5
AE, adverse event; bEOS, blood eosinophil; ED, emergency department; EOT, end of treatment; ER, event rate per 100 patient-years; EU, European Union; Exp, exposure; FEV1, forced expiratory volume in 1 second; GINA, Global Initiative for Asthma; HD-ICS, high-dose inhaled corticosteroid; ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; OCS, oral corticosteroid; PAO, persistent airflow obstruction; PBO, placebo; Q4W, every 4 weeks; Q8W, every 8 weeks; SAE, serious adverse event; 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. 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. 5. Korn S, Bourdin A, Chupp G, et al. Integrated safety and efficacy among patients receiving benralizumab for up to 5 years. J Allergy Clin Immunol Pract. 2021;9(12):4381-4392.e4. 6. Busse WW, Bleecker ER, FitzGerald JM, et al; BORA study investigators. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir Med. 2019;7(1):46-59.
