FASENRA STUDIES
MANDARA Pivotal Phase 3 Trial
In the MANDARA pivotal trial (52 weeks), FASENRA demonstrated noninferiority to mepolizumab for the primary endpoint of remission and the components of remission. 59% remission at Weeks 36 and 48 (n=41) with FASENRA and 57% with mepolizumab (n=40).1,2
- MANDARA was a 52-week, randomized, double-blind, active-controlled, head-to-head noninferiority trial comparing the efficacy and safety of FASENRA to mepolizumab in adult patients with relapsing or refractory EGPA1-4
- At the end of the double-blind period, 128 patients entered the open-label extension (OLE) for at least 1 year. Patients either continued on FASENRA or switched from mepolizumab to FASENRA1-4
Key OLE Limitations: The OLE period only included FASENRA treatment arms. Treatment with mepolizumab was not assessed during the OLE period. The impact of remission and steroid reduction compared to FASENRA at 2 years remains unknown.4
Clinical Data in MANDARA Noninferiority Trial
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MANDARA is the pivotal 52-week, Phase 3, randomized, double-blind, multicenter, active-controlled, head-to-head noninferiority trial comparing the efficacy and safety of FASENRA to mepolizumab in adult patients with relapsing or refractory EGPA. 140 patients were randomized 1:1 to receive FASENRA (one 30-mg SC injection + 3 matching placebo injections; Q4W) or mepolizumab (three 100-mg SC injections + 1 matching placebo SC injection; Q4W).1-4
Following completion of the double-blind period, 128 patients entered the open-label extension of at least 1 year in duration. Patients either continued on FASENRA or switched from mepolizumab to FASENRA. Efficacy and safety of FASENRA and the mepolizumab to FASENRA switch arms were examined during the combined double-blind period and the first year of the ongoing open-label extension of the MANDARA trial.1-4
Study Design2,4
Select endpoints1-4
- Proportion of patients achieving remission (BVAS=0 and OCS dose ≤4 mg/day) at Weeks 36 and 48 (primary endpoint), Week 52, and Week 104
- Sustained remission (defined as remission at Week 24 maintained until Week 104)
- Relapses
- Complete withdrawal of OCS use
- Blood eosinophil count
- Adverse events
Primary endpoint (double-blind primary analysis)1,2
FASENRA demonstrated noninferiority to mepolizumab for the primary endpoint of remission and the components of remission.1,2
Primary endpoint results1,2:
59% remission with FASENRA (n = 41)
and 57% remission with mepolizumab (n =
40)
at Weeks 36 and 48
Remission was defined as BVAS=0 and OCS ≤4 mg/day at Weeks 36 and 48.1,2
Results in patients who completed the double-blind study then entered the OLE.* The OLE was conducted to assess the safety and tolerability of FASENRA in EGPA.2 All patients received FASENRA in the open-label extension phase of the study.4
*Out of those patients who completed the noninferiority, double-blind MANDARA study, 128 patients opted to enter the OLE and continued to receive (n=66) or started FASENRA (n=62) at Week 52. Remission rates were analyzed for patients who were in both arms of the study.4
OLE period analysis data4
Proportion of patients in remission by time point*
Results are descriptive only.
*Remission defined as BVAS=0 and OCS ≤4 mg/day; OLE analysis set.4
OLE period analysis data4
Note: Error bars represent IQR.
Results are descriptive only.
Secondary endpoint and post hoc data (primary analysis)2
- In the MANDARA study, relapse was observed in 30% of patients on FASENRA and 30% of patients on mepolizumab2
Relapses in all patients in both treatment groups combined during the double-blind period5
A total of 42 patients had a relapse; one patient could have several events.
OLE period analysis data4
- During the open-label extension period, 77.3% of patients who continued on FASENRA (n/N=51/66), and 67.7% of patients who started on FASENRA (n/N=42/62) had no relapses4
Results are descriptive only.
Relapse was defined as the presence of one of the following: active vasculitis (BVAS of >0); active asthma symptoms, signs, or both with a corresponding worsening score on the ACQ-6; active nasal disease, sinus disease, or both with a corresponding worsening reflected by responses to at least one of the questions on the Sino-nasal Symptoms Questionnaire and an increase in the total daily dose of oral glucocorticoid therapy to >4 mg of prednisolone per day; an increase in the dose of or the addition of immunosuppressive therapy; or hospitalization related to worsening of EGPA.2
Secondary endpoint (double-blind primary analysis)1-3
0-mg daily OCS dose during Weeks 48 through 52: 41% of patients on FASENRA (n=29/70) vs 26% on mepolizumab (n=18/70).1-3
The OCS dose was tapered at the discretion of the investigator.4
Results are descriptive only.
These results were not statistically significant as there was no prespecified multiple testing procedure.4
Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. Decrease corticosteroids gradually, if appropriate.
Safety data
(MANDARA study)
Resources
Pivotal Study Design
MANDARA Trial1-4
MANDARA (52 weeks) is a Phase 3, multicenter, double-blind, randomized, active-controlled, head-to-head, noninferiority trial evaluating the efficacy and safety of FASENRA 30 mg SC compared to mepolizumab 300 mg SC every 4 weeks. A total of 140 patients aged 18 years and older with an EGPA diagnosis and a history of relapsing or refractory disease who were receiving standard care underwent randomization in a 1:1 ratio to receive FASENRA or mepolizumab.1-4
The primary endpoint was remission (BVAS=0 and OCS ≤4 mg per day) at Weeks 36 and 48. Secondary endpoints included total accrued duration of remission, remission within the first 24 weeks and maintenance of remission to Week 52, the time from randomization to first relapse, major relapse, the frequency of relapse during the double-blind period, and the average daily oral glucocorticoid dose during Weeks 48 through 52.1-3
ACQ-6, Asthma Control Questionnaire-6; BVAS, Birmingham Vasculitis Activity Score; EGPA, eosinophilic granulomatosis with polyangiitis; IQR, interquartile range; OCS, oral corticosteroid; OLE, open-label extension; Q4W, every 4 weeks; SC, subcutaneous.
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. Wechsler ME, Nair P, Terrier B, et al. Benralizumab versus mepolizumab for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2024;390(10):911-921. 3. Wechsler ME, Nair P, Terrier B, et al. Benralizumab versus mepolizumab for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2024;390(10)(suppl):1-46. 4. Merkel PA, Nair PK, Khalidi N, et al. Two-year efficacy and safety of anti-interleukin-5/receptor therapy for eosinophilic granulomatosis with polyangiitis. Ann Rheum Dis. 2025;84(11):1888-1899. 5. Merkel PA, Jayne DRW, Specks U, et al. Characteristics of relapses in patients with eosinophilic granulomatosis with polyangiitis. Poster presented at: American College of Rheumatology (ACR) Convergence 2024; November 14–19, 2024; Washington, DC. Poster 1605.
