Introduction
Fasenra (benralizumab) is a humanized monoclonal antibody approved for the add-on maintenance treatment of severe eosinophilic asthma in patients aged 12 years and older. Manufactured by AstraZeneca, it represents a targeted biologic therapy that specifically addresses the underlying eosinophilic inflammation pathway in severe asthma.
Mechanism of Action
Fasenra exerts its therapeutic effect through targeted interleukin-5 (IL-5) receptor alpha-directed cytolytic monoclonal antibody activity. The drug binds specifically to the alpha subunit of the human IL-5 receptor, which is expressed on eosinophils and basophils. This binding induces antibody-dependent cell-mediated cytotoxicity (ADCC) through natural killer (NK) cells, resulting in rapid and near-complete depletion of eosinophils and basophils. Unlike other IL-5 inhibitors that merely block IL-5 signaling, benralizumab's unique mechanism directly eliminates these inflammatory cells.
Indications
Fasenra is FDA-approved for:
- Add-on maintenance treatment of severe asthma in patients 12 years and older with an eosinophilic phenotype
- Patients with a history of asthma exacerbations despite high-dose inhaled corticosteroids plus additional controller medications
The European Medicines Agency has similarly approved benralizumab for severe eosinophilic asthma in patients 12 years and older inadequately controlled with high-dose inhaled corticosteroids plus long-acting beta-agonists.
Dosage and Administration
Standard dosing: 30 mg administered subcutaneously every 4 weeks for the first 3 doses, followed by 30 mg every 8 weeks thereafter. Administration:- Administer by subcutaneous injection in the abdomen, thigh, or upper arm
- Prefilled syringe should be allowed to reach room temperature (30 minutes) before administration
- Do not shake the prefilled syringe
- Rotate injection sites
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Pediatric: Safety and effectiveness established for patients 12 years and older
- Geriatric: No overall differences in safety or effectiveness observed
- Pregnancy: Limited data available - use only if potential benefit justifies potential risk
- Lactation: No data on presence in human milk - consider developmental and health benefits versus potential risk
Pharmacokinetics
Absorption: Following subcutaneous administration, benralizumab is absorbed with median time to maximum concentration of approximately 5 days. Bioavailability is approximately 58%. Distribution: Steady-state volume of distribution is approximately 6.3 L. Benralizumab binds specifically to the IL-5 receptor alpha subunit on eosinophils and basophils. Metabolism: Benralizumab is expected to be metabolized via proteolytic enzymes throughout the body, similar to other immunoglobulin G1 monoclonal antibodies. Elimination: Elimination occurs primarily through intracellular catabolism following binding to IL-5 receptors. The terminal half-life is approximately 15.5 days. No clinically significant differences in pharmacokinetics were observed based on age, gender, race, or body weight.Contraindications
- History of hypersensitivity to benralizumab or any of its excipients
- Active helminth infections (should be treated prior to initiation)
Warnings and Precautions
Hypersensitivity reactions: Hypersensitivity reactions (including anaphylaxis, angioedema, urticaria, and rash) have been reported. Discontinue immediately if hypersensitivity reaction occurs. Acute asthma symptoms: Not for treatment of acute asthma symptoms, acute bronchospasm, or status asthmaticus. Reduction of corticosteroid therapy: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation. Reduce corticosteroids gradually under medical supervision. Parasitic (helminth) infections: Treat pre-existing parasitic infections before initiating therapy. Patients living in endemic areas or with suspected infections should be monitored during treatment. Immunogenicity: Patients may develop anti-drug antibodies, which could affect pharmacokinetics, safety, and efficacy.Drug Interactions
Live vaccines: Avoid administration of live vaccines in patients treated with Fasenra. The effect on immune responses to non-live vaccines is unknown. Corticosteroids: Caution when reducing corticosteroid dosage due to risk of adrenal insufficiency.No formal drug interaction studies have been conducted. Based on its mechanism of action, no pharmacokinetic interactions with small molecule drugs are expected.
Adverse Effects
Most common adverse reactions (≥5%):- Headache (8%)
- Pharyngitis (6%)
- Pyrexia (5%)
- Hypersensitivity reactions
- Herpes zoster infections
- Injection site reactions (pain, erythema, pruritus, swelling)
- Increased eosinophil counts (transient, following initiation)
- Fatigue
- Bronchitis
- Arthralgia
- Back pain
- Dizziness
- Allergic rhinitis
- Urinary tract infection
Monitoring Parameters
Baseline:- Absolute eosinophil count
- Asthma control assessment (ACT score, exacerbation history)
- Pulmonary function tests (FEV1)
- Corticosteroid usage
- Screening for parasitic infections in endemic areas
- Asthma symptom control and exacerbation frequency
- Pulmonary function (FEV1)
- Reduction in corticosteroid requirements
- Signs of hypersensitivity reactions
- Development of infections, particularly herpes zoster
- Injection site reactions
- Periodic eosinophil counts (may show transient increase initially)
- Continued assessment of asthma control
- Monitoring for development of anti-drug antibodies in cases of reduced response
Patient Education
Administration:- Instruct on proper subcutaneous injection technique if self-administering
- Demonstrate how to use the prefilled syringe
- Emphasize importance of rotating injection sites
- Explain the loading dose schedule (every 4 weeks x 3) followed by maintenance dosing (every 8 weeks)
- Fasenra is not a rescue medication and should not be used for acute symptoms
- Improvement in asthma control may take several weeks to months
- Do not stop controller medications unless instructed by healthcare provider
- Report any signs of allergic reaction (rash, swelling, difficulty breathing) immediately
- Inform healthcare providers about all medications being taken
- Seek immediate medical attention for asthma attacks or worsening symptoms
- Report any signs of infection, especially shingles (painful rash with blisters)
- Inform healthcare provider if pregnant, planning pregnancy, or breastfeeding
- Store refrigerated at 2°C to 8°C (36°F to 46°F)
- Keep in original carton to protect from light
- Do not freeze
- May be stored at room temperature up to 25°C (77°F) for up to 14 days
References
1. FDA Prescribing Information: Fasenra (benralizumab). 2022. 2. Bleecker ER, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-2127. 3. FitzGerald JM, et al. 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, et al. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med. 2014;2(11):891-901. 5. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention, 2022. 6. European Medicines Agency. Fasenra (benralizumab) Summary of Product Characteristics. 2022.