Becker's Hospital Review

bEOS = blood eosinophils; FEV 1 = forced expiratory volume in 1 second; HD-ICS = high-dose inhaled corticosteroid; LABA = long-acting ß 2 -agonists; Q4W = every 4 weeks; Q8W = every 8 weeks; SC = subcutaneous. FASENRA is a registered trademark of the AstraZeneca group of companies. ©2023 AstraZeneca. All rights reserved. US-79385 8/23 PLEASE SEE BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION ON ADJACENT PAGES. You are encouraged to report the negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088. 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%) include headache and pharyngitis. 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. USE IN SPECIFIC POPULATIONS A pregnancy exposure registry monitors pregnancy outcomes in women exposed to FASENRA during pregnancy. To enroll call 1-877-311-8972 or visit www.mothertobaby.org/fasenra. 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. INDICATION FASENRA is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. • FASENRA is not indicated for treatment of other eosinophilic conditions • FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus STUDY DESIGNS SIROCCO (Trial 1) 1,2 SIROCCO (48-week) was a randomized, double-blind, parallel-group, placebo-controlled, multicenter study 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 patients aged 12 to 75 years old with severe asthma uncontrolled on HD-ICS and 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 bEOS counts (≥300 cells/μL and <300 cells/μL). The primary endpoint was annual exacerbation rate ratio vs placebo in patients with bEOS counts of ≥300 cells/μL on HD-ICS/LABA. Exacerbations were 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. Key secondary endpoints were prebronchodilator FEV1 and total asthma symptom score at Week 48 in the same population. ZEPHYR 2 3,4 ZEPHYR 2 was a retrospective cohort study utilizing claims data between 2016-2020 from a large US payer dataset, examining effectiveness of FASENRA in patients with asthma. 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. 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. 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 naïve and focused on patients with ≥2 records of FASENRA. Subgroups included a persistent cohort (≥6 records of FASENRA, n=708) and a OCS-dependent cohort (patients with a cumulative dose of ≥450mg prednisone equivalent OCS over 90 consecutive days or ≥180-day supply of OCS during the 12-month pre-index period, n=1065). Additional cohorts included patients who switched to FASENRA from omalizumab (n=205) or mepolizumab (n=144), and a cohort stratified by blood eosinophil level (n=429). 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 payer data The exact reasons behind a patient's switch from one medication to another cannot be ascertained from the data This is an observational study; clinical implications cannot be determined from this payer database study References: 1. FASENRA® (benralizumab) [package insert]; Wilmington, DE: AstraZeneca Pharmaceuticals LP; February 2021; 2. Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting ß 2 -agonists (SIROCCO): a randomised, multicentre, placebo-controlled Phase 3 trial. Lancet. 2016;388:2115-2127; 3. Maselli DJ, et al. Poster Presentation at American College of Allergy, Asthma, and Immunology Meeting 2021; November 4-8, 2021 4. Carstens D, Maselli D, Yang D, et al. Reduction in asthma exacerbations from ZEPHYR 2 – largest RWE study on benralizumab [poster]. Presented at: American Academy of Allergy, Asthma & Immunology (AAAAI) Meeting; February 25-28, 2022; Phoenix, AZ. FASENRA® (benralizumab) Subcutaneous Injection 30 mg

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