Benralizumab

Introduction Overview

Generic Name

benralizumab

Brand Name

Fasenra

Dosage Form

injection for subcutaneous use

Drug Class

Interleukin inhibitors

Pharmacokinetics

Absorption:
Benralizumab is administered via subcutaneous injection, which allows for gradual absorption into systemic circulation. Following subcutaneous administration, peak serum concentrations are typically reached within 2 to 8 days, indicating a relatively slow but sustained absorption phase. The bioavailability of benralizumab is approximately 58%, consistent with other monoclonal antibodies administered subcutaneously. Factors such as injection site and local blood flow may influence absorption kinetics.

Distribution:
Benralizumab exhibits a limited volume of distribution reflective of its antibody nature, primarily remaining in the vascular and extracellular fluid compartments. The estimated volume of distribution at steady state ranges from 4 to 6 liters, indicating minimal tissue penetration outside plasma and interstitial fluids. Benralizumab does not cross the blood-brain barrier significantly. Binding is highly specific to the IL-5 receptor alpha on eosinophils, with negligible non-specific binding to other tissues.

Metabolism:
As a monoclonal antibody, benralizumab is metabolized via proteolytic degradation to small peptides and amino acids through ubiquitous lysosomal catabolic pathways in the reticuloendothelial system and target-mediated internalization. It does not undergo hepatic metabolism via cytochrome P450 enzymes. Metabolic clearance is influenced by target binding and immune complex formation, leading to internalization and catabolism.

Elimination:
Benralizumab clearance is characterized by a dual pathway involving both target-mediated drug disposition and non-specific clearance mechanisms. The serum elimination half-life is approximately 15 to 20 days, consistent with IgG1 subclass antibodies. Clearance may be affected by the abundance of IL-5 receptor-positive eosinophils and the patient’s immune status. Benralizumab is not excreted renally or hepatically as intact molecule but after proteolytic catabolism.

Dosage Forms

Available Dosage Forms:
Fasenra is supplied as a solution for subcutaneous injection in the following forms:
- Single-dose prefilled syringe:
- 10 mg/0.5 mL
- 30 mg/mL
- Single-dose autoinjector (Fasenra Pen):
- 30 mg/mL

Dosages for Adults and Adolescents:
- For severe eosinophilic asthma in adults and adolescents aged 12 years and older: 30 mg subcutaneously once every 4 weeks for the initial 3 doses, followed by once every 8 weeks thereafter.
- For eosinophilic granulomatosis with polyangiitis (EGPA) in adults: 30 mg subcutaneously every 4 weeks.

Dosages for Pediatric Populations:
- For children aged 6 through 11 years with eosinophilic asthma:
- Weighing less than 35 kg: 10 mg subcutaneously once every 4 weeks for the first 3 doses, then every 8 weeks.
- Weighing 35 kg or more: 30 mg subcutaneously once every 4 weeks for the first 3 doses, then every 8 weeks.
- Fasenra is not approved for children under 6 years for eosinophilic asthma.

Specific Patient Populations:
- The dosing regimen may be individualized based on body weight in pediatric patients.
- Patients should be monitored for eosinophil levels to guide therapy duration.
- Administration sites should be rotated between the front of the thigh and lower abdomen; caregivers may administer injections in the upper arm.
- Not intended for acute asthma attacks; fast-acting inhalers remain the rescue treatment.

Mechanism Of Action

Benralizumab, marketed as Fasenra, is a humanized monoclonal antibody that selectively targets the alpha subunit of the interleukin-5 receptor (IL-5Rα) expressed on eosinophils and basophils. IL-5 is the primary cytokine responsible for the differentiation, survival, recruitment, and activation of eosinophils, which are key inflammatory cells implicated in eosinophilic asthma and eosinophilic granulomatosis with polyangiitis (EGPA). By binding with high affinity to IL-5Rα, benralizumab effectively prevents IL-5 from engaging its receptor, thereby disrupting eosinophil maturation and function.

Beyond simple receptor blockade, benralizumab possesses an afucosylated Fc region which enhances its interaction with Fc gamma receptor IIIa (FcγRIIIa) on natural killer (NK) cells. This modification significantly increases antibody-dependent cell-mediated cytotoxicity (ADCC). Consequently, benralizumab promotes the rapid depletion of eosinophils and basophils by inducing NK cell-mediated apoptosis, both in the bloodstream and peripheral tissues. This dual mechanism leads to near-complete eradication of eosinophils that are centrally involved in airway inflammation and tissue damage.

Clinically, the depletion of eosinophils results in reduced airway hyperresponsiveness, mucus production, and inflammation, which translates into fewer asthma exacerbations and improved pulmonary function. Fasenra’s rapid and sustained eosinophil depletion has been demonstrated in clinical trials, with significant reductions evident within 24 hours post-dose. Compared with other anti-IL-5 therapies, such as mepolizumab and reslizumab which neutralize IL-5 cytokine, benralizumab’s IL-5Rα targeting and enhanced ADCC offer a distinctive and potent means to eliminate eosinophils effectively.

Research evidence including pivotal phase III trials supports the clinical efficacy of benralizumab in reducing severe asthma exacerbations, decreasing oral corticosteroid use, and improving quality of life in patients with eosinophilic asthma. Furthermore, recent FDA approval for EGPA highlights benralizumab’s mechanism as a beneficial therapeutic strategy in systemic eosinophilic diseases, offering a targeted approach to immunomodulation.

Pharmacological Actions

Selective binding to interleukin-5 receptor alpha (IL-5Rα) on eosinophils and basophils.
Induction of antibody-dependent cell-mediated cytotoxicity (ADCC) via enhanced NK cell recruitment.
Rapid depletion of circulating and tissue eosinophils, reducing inflammatory cell burden.
Inhibition of IL-5 mediated eosinophil maturation, recruitment, and survival.
Reduction of airway inflammation associated with eosinophilic asthma.
Amelioration of eosinophil-driven tissue damage in eosinophilic granulomatosis with polyangiitis.
Long half-life supporting extended dosing intervals for sustained eosinophil suppression.
Does not interfere with other immune cells, maintaining general immune competence.
Provides a steroid-sparing effect by reducing the need for systemic corticosteroids.
Facilitates improved lung function and reduced asthma exacerbation rates in clinical studies.
Targeted immunomodulation without broad immunosuppression.
Well-tolerated with a favorable safety profile in controlled trials.
Depletes eosinophils without affecting neutrophils or other leukocytes.
Afucosylation of Fc region enhances NK cell-mediated cytotoxicity effect.
Does not cross-react with other interleukin receptors, minimizing off-target effects.

Therapeutic Or Clinical Uses

Add-on maintenance treatment for severe eosinophilic asthma in adults and adolescents aged 12 years and older.
Treatment of severe eosinophilic asthma in children aged 6 through 11 years with specific weight-based dosing.
Management of eosinophilic granulomatosis with polyangiitis (EGPA) in adults as an adjunct therapy.
Reduction of asthma exacerbations in patients not adequately controlled by standard therapies.
Steroid-sparing agent to decrease the use of oral corticosteroids in severe eosinophilic asthma.
Improvement of lung function and respiratory symptoms in eosinophilic asthma patients.
Targeted depletion of eosinophils to control airway and tissue inflammation.
Adjunctive therapy to standard inhaled corticosteroids and bronchodilators.
Potential treatment option in relapsing or refractory EGPA cases.
Clinical benefit in reducing healthcare utilization for severe asthma exacerbations.
Treatment in patients with an eosinophil count of at least 150 cells/μL generally considered for therapy.
Option for patients who have failed or are intolerant to other biologic asthma therapies.
Use in patients requiring frequent oral corticosteroid bursts to control eosinophilic inflammation.
Treatment that can be administered conveniently with infrequent subcutaneous injections.
Therapeutic utility supported by FDA approvals and robust clinical trial data.

Side Or Adverse Effects

Headache, a commonly reported side effect experienced shortly after administration.
Sore throat (pharyngitis), possibly related to immune modulation.
Injection site reactions including redness, swelling, itching, or pain.
Allergic hypersensitivity reactions ranging from mild rash to severe anaphylaxis.
Potential for transient flu-like symptoms including malaise and fever.
Rare cases of angioedema involving swelling of face, mouth, and tongue.
Possible dizziness or syncope related to hypersensitivity or vasovagal response.
Hives (urticaria) indicative of allergic responses.
Respiratory symptoms including shortness of breath due to immune reactions.
Risk of parasitic infections may theoretically increase due to eosinophil depletion.
No significant evidence of immunosuppression-related infections in current data.
Potential exacerbation of pre-existing helminth infections if untreated prior to therapy.
Delayed onset hypersensitivity reactions reported hours to days post-injection.
Headache and sore throat are the most commonly documented adverse events in clinical trials.
Injection device-related adverse events such as device failure or incorrect administration.

Precautions

Ensure patient allergy status to benralizumab or any formulation components before initiation.
Screen for parasitic (helminth) infections and treat infections prior to therapy initiation.
Do not abruptly discontinue corticosteroid therapy without consulting healthcare provider.
Monitor eosinophil counts to assess treatment effectiveness and disease control.
Educate patients that Fasenra is not a rescue medication for acute asthma attacks.
Patients should seek immediate medical attention if symptoms of hypersensitivity develop.
Use caution in pregnant or breastfeeding women; discuss risks and benefits thoroughly.
Avoid injections at sites with skin lesions, bruising, or scarring to reduce injection complications.
Maintain proper injection site rotation to minimize local skin reactions.
Ensure caregiver or healthcare provider training if self-administration is planned, especially for pediatric patients.
Consider evaluation of immunization status prior to therapy; live vaccines should be avoided.
Monitor for potential delayed allergic reactions after injection, even if initial tolerance is apparent.
Regular follow-up is essential to assess disease status and adverse effects.
Inform patients about the importance of continuing other asthma medications unless directed otherwise.
Use caution in patients with cardiovascular or other systemic illnesses; monitor closely.

Warnings

Risk of serious hypersensitivity reactions including anaphylaxis; immediate medical attention required if symptoms occur.
Fasenra is not indicated for children under 6 years for asthma or under 18 years for EGPA.
Not a rescue medication—patients must use standard fast-acting inhalers for acute asthma exacerbations.
Potential immunogenicity leading to anti-drug antibodies may reduce drug efficacy or cause reactions.
Patients with parasitic infections may experience exacerbations; treat prior to initiation.
Do not shake the Fasenra injection pen to preserve biologic integrity.
Discard the Fasenra Pen if it has been frozen, damaged, or beyond expiration date.
Use caution in patients with history of severe hypersensitivity to monoclonal antibodies.
Potential for injection site infections or reactions necessitates aseptic injection techniques.
Avoid use in patients with active untreated helminth infections.
Patients should be observed for a sufficient period after injection for signs of allergic reaction.
Potential delayed immune reactions may occur hours to days post-dose.
Fasenra use during pregnancy should be considered only if potential benefit justifies potential risk.
Breastfeeding women should discuss treatment with healthcare provider due to unknown excretion in milk.
Patients should not share injection devices to prevent transmission of infections.

Contraindication

Known hypersensitivity to benralizumab or any excipients in the formulation.
History of anaphylactic or severe allergic reaction to prior Fasenra administration.
Do not use as monotherapy for acute bronchospasm or status asthmaticus requiring emergency treatment.
Children under 6 years of age for eosinophilic asthma due to lack of safety and efficacy data.
Adolescents and children under 18 years for eosinophilic granulomatosis with polyangiitis (EGPA).
Patients with active untreated parasitic (helminth) infections until infection resolution.
Use in patients with known immunodeficiency disorders is not recommended without close monitoring.
Concomitant use with other biologics targeting IL-5 pathway has not been established and should be avoided.
Contraindicated in patients with serious hypersensitivity reactions to monoclonal antibody therapies with similar structures.
Patients with severe, uncontrolled asthma exacerbations requiring intensive care should not initiate therapy without stabilization.
Known severe hypersensitivity to any monoclonal antibodies or protein-based therapies.
Use is not indicated for non-eosinophilic asthma phenotypes.
Avoid use if injection device or medication shows signs of tampering or compromise.
Contraindicated if patient is unable to self-administer or lacks caregiver support without healthcare professional assistance.
Contraindications may expand with emerging safety data; clinicians should review updated prescribing information.

Drug Interactions

No significant drug interactions have been established with commonly used asthma medications.
Benralizumab does not undergo cytochrome P450 metabolism, reducing potential for metabolic drug interactions.
Concomitant use of immunosuppressants or other biologics should be carefully monitored for additive immunosuppression.
No evidence of interaction with oral or inhaled corticosteroids, although corticosteroids should not be discontinued abruptly.
No known interactions with antihistamines, bronchodilators, or leukotriene receptor antagonists.
Interactions with herbal supplements, vitamins, and over-the-counter medications have not been reported but should be disclosed to healthcare providers.
Vaccination responses may be affected; avoid live vaccines during treatment and consult immunization guidelines.
Concomitant use with other IL-5 pathway inhibitors lacks clinical data and is generally not recommended.
Drug interaction reports do not identify significant effects on warfarin or anticoagulants.
No pharmacokinetic interactions expected based on monoclonal antibody characteristics.
Potential immunomodulation may theoretically alter response to infectious disease agents or vaccines.
Inform healthcare providers about all medications to facilitate assessment of possible interactions.
No dose adjustment recommended when co-administered with other asthma treatment regimens.
Monitoring advised if new systemic therapies are started during benralizumab treatment.
Comprehensive interaction studies remain limited due to the biologic nature of benralizumab.

Preparations Of The Drug

Fasenra 10 mg/0.5 mL solution in single-dose prefilled syringe for subcutaneous injection.
Fasenra 30 mg/mL solution in single-dose prefilled syringe for subcutaneous injection.
Fasenra 30 mg/mL solution in single-dose autoinjector device (Fasenra Pen) for subcutaneous use.
Prefilled syringes and autoinjector pens designed for single administration and ease of patient or caregiver use.
Specific excipients include L-histidine, L-histidine hydrochloride monohydrate, polysorbate 20, α,α-trehalose dihydrate, and Water for Injection.
Storage requires refrigeration at 2°C to 8°C (36°F to 46°F) in original carton until use, with allowance for up to 14 days at room temperature (20°C to 25°C).
Each dose is provided in a sterile, single-use format to prevent contamination and dosing errors.
Provision for patient or caregiver administration training is recommended before home use.
Packaging includes tamper-evident seals and detailed instructions for correct injection technique.
Disposal of used injection devices should be performed in puncture-resistant sharps containers.
Fasenra preparations are free from preservatives and must not be shaken to preserve protein integrity.
No biosimilar products currently approved that match Fasenra formulations; AstraZeneca holds proprietary rights.
Labels indicate lot number, expiration date, and storage requirements to ensure quality and efficacy.
Preparation and administration should be performed under aseptic conditions to maintain sterility.
Patient information leaflets accompany each preparation to provide guidance on use, precautions, and side effects.