Dr. K. V. Subba Reddy Institute of Pharmacy.
This comprehensive review explain that the drug profile of benralizumab, a monoclonal antibody approved by the FDA for the management of severe eosinophilic asthma and other eosinophilic conditions. Highlighting asthma as a chronic inflammatory disorder characterized by eosinophilic excess, the review classifies treatment options including corticosteroids, leukotriene modifiers, biologics, and bronchodilators. Specifically focusing on benralizumab, the review details its mechanism of action as an IL-5 receptor antagonist, leading to eosinophil depletion via apoptosis and antibody-dependent cell-mediated cytotoxicity. The pharmacokinetic properties reveal a dose-proportional profile with a half-life of 15.5 days and prevalent routes of administration by subcutaneous injection. Compared to mepolizumab, benralizumab demonstrates superior efficacy in reducing exacerbations and improving lung function, particularly in patients with elevated eosinophil counts. Despite its therapeutic advantages, potential adverse effects such as hypersensitivity reactions necessitate careful patient monitoring. This review emphasizes the significance of benralizumab as a targeted therapy in eosinophilic asthma, advocating for its role in clinical practice while recognizing the importance of ongoing assessment for optimal patient outcomes.
Asthma is a chronic respiratory condition that affects people of all ages. It is caused by inflammation and muscle stiffness in the airways, making it difficult to breathe.1 Eosinophilic asthma is characterized by elevated amounts of eosinophils, a kind of immune cell. High eosinophil levels can lead to airway irritation. Having an irritated airway can cause asthma symptoms and attacks. Eosinophilic asthma commonly begins in maturity. It might be allergic or non-allergic asthma. This means that allergens may or may not produce symptoms. It is frequently associated to chronic sinusitis and nasal polyps.2
Classification (Based on treatment)
Corticosteroids, leukotriene modifiers, biologics, and bronchodilators are some of the medications used to treat eosinophilic asthma.3
Corticosteroids
Corticosteroids can be administered orally or by inhalation.
Can have mild to severe negative effects.
Inhaled corticosteroids may be ineffective for certain patients.4
Leukotriene Modifiers:
Can lower the quantity of eosinophils in the airways.5
Biologics
A type of medicine produced by living creatures, such as bacteria, plants, or animals.
work by disrupting cells or inhibiting certain chemicals that cause inflammation.
Examples include anti-thymic stomal lymphopoietin (anti-TSLP), anti-IgE, and anti-IL-4R alpha.6
Bronchodilators
Include beta 2 agonists and anticholinergics.
Can be consumed orally, inhaled, or injected.7
Drug Description on Benralizumab
The FDA approved benralizumab (fasenra) for treating severe eosinophilic asthma in patients 6 years and older, as well as for treating EGPA vasculitis.8
Benralizumab for Eosinophilic asthma
In 2017, the FDA authorized benralizumab for individuals 12 years or older with severe eosinophilic asthma.9 On November 14, 2017, the FDA authorized Fasenra (benralizumab) to treat severe eosinophilic asthma.10 October 4, 2019 FDA authorizes fasenra pen prefilled auto injector for self-administration.11
In 2024, the FDA authorized benralizumab for patients 6 to 11 years old with severe eosinophilic asthma.12 Apr 11, 2024 Fasenra is approved for the treatment of severe asthma in children aged six to eleven.
Sep 18, 2024 Fasenra approved in the US for eosinophilic granulomatosis with polyangiitis.
Benralizumab, commercialized as Fasenra, is a monoclonal antibody directed against the alpha chain of the interleukin-5 receptor (CD125).
The US Food and Drug Administration authorized it in November 2017 as a therapy for severe eosinophilic asthma. In August 2019, the Food and medication Administration designated it an orphan medication for the treatment of eosinophilic esophagitis. 13
Benralizumab is a monoclonal antibody. It is an injectable medicine used as an adjunct therapy to treat eosinophilic asthma, a chronic inflammatory illness that causes your airways to narrow and swell, making breathing difficult.14
Advantages Of Benralizumab Over Mepolizumab
Table 1: Advantages of benralizumab over mepolizumab15
|
Monoclonal |
Target |
Indication |
Dose |
Other information |
|
Benralizumab |
Binds to IL-5 receptor on eosinophils and basophils, leading to apoptosis |
Add-on maintenance treatment in adult patients with severe eosinophilic asthma inadequately controlled despite high-dose inhaled corticosteroids plus long-acting beta-agonists |
30mg by subcutaneous injection every 4 weeks for the first 3 doses then every 8 weeks thereafter |
Available as prefilled pen or syringe
Review benefit of treatment annually |
|
Mepolizumab |
Binds to IL-5, preventing interaction with receptor on surface of eosinophils |
Add-on treatment for severe refractory eosinophilic asthma in adults, adolescents and children aged 6 years and older |
Child 6–11 years: 40mg ≥12s and adults: 100mg Both by subcutaneous injection every 4 weeks |
Available in vials for reconstitution, or as a prefilled pen or syringe Review benefit of treatment annually |
Benralizumab was particularly beneficial in those with an eosinophil level of 150-299 cells/mcL. Benralizumab's superior efficacy in this group of patients may be attributed to IL5 receptor blockage, which typically results in near-complete eosinophil reduction. In a Bayesian network meta-analysis of eosinophilic asthma, benralizumab outperformed mepolizumab in terms of lowering exacerbations, improving FEV1, and depleting blood eosinophils.16
Pharmacology Of Benralizumab
Mechanism of action
IgG1, kappa monoclonal antibody benralizumab induces eosinophil and basophil death via antibody-dependent cell-mediated cytotoxicity. 17
Pharmacokinetics Of Benralizumab
Administration
Benralizumab's dose-proportional pharmacokinetic profile was demonstrated by subcutaneous injection. With a bioavailability of 58%, the administration of 20–200 mg showed an absorption half-life of 3.6 days. AUC of 775 mcg day/ml and Cmax of 82 mcg/ml are also recorded for benralizumab.18
Bioavailability, subQ: 59% regardless of subQ injection site
Distribution
Vd: 3.1 L (central); 2.5 L (peripheral)
Metabolism
Body: Widely by proteolytic enzymes
Excretion
Total body clearance, asthma: 0.29 L/day
Total body clearance, eosinophilic granulomatosis with polyangiitis: 0.22 L/day
Elimination Half Life
15.5 days17
Pharmacodynamics
The primary target of inflammatory respiratory disorders are eosinophils, which suffer apoptosis when IL-5 is not present. Consequently, benralizumab causes apoptosis and a notable decrease in blood via acting on the IL-5 receptor in basophils and eosinophils. However, when benralizumab binds to the FcγRIIIα receptor on natural killer cells, it causes direct antibody-dependent cell-mediated cytotoxicity. As a result of all these effects, the eosinophil count in the bone marrow, blood, sputum, submucosa, and airway mucosa decreases.18
Dosage For Benralizumab
The recommended dose of benralizumab is 30 mg every 4 weeks for the first 3 doses, followed by once every 8 weeks thereafter.19
Benralizumab is administered by subcutaneous injection.
Usual Dose for Asthma
30 mg subcutaneously once every 4 weeks for the first 3 doses, then once every 8 weeks thereafter
This drug should be injected into the upper arm, thigh, or abdomen.
For add-on maintenance therapy of patients with severe asthma with an eosinophilic phenotype20
Adverse Drug Reactions
Serious adverse effects from benralizumab include: allergic (hypersensitive) responses, which might include anaphylaxis. After receiving an injection of benralizumab, you may experience severe allergic reactions. After receiving an injection, allergic responses might occasionally occur hours or days later. If you experience any of the following signs of an allergic reaction, notify your healthcare practitioner or seek emergency assistance immediately:
swelling in your mouth, tongue, and face
breathing issues dizziness, lightheadedness, and fainting (low blood pressure)
rash hives Benralizumab's most frequent adverse effects include sore throat and headache.
Benralizumab side effects are not limited to these. 19
Contraindications
Hypersensitivity to benralizumab or any component of the product17
Indication
In addition to potentially improving breathing, benralizumab is prescribed to avoid severe asthma attacks, or exacerbations.17
Warnings And Precautions
Hypersensitivity Reactions
Anaphylaxis, angioedema, urticaria, and rash are examples of hypersensitivity reactions that have happened after FASENRA was administered. Though they might start days later, these reactions usually happen within hours after ingestion. FASENRA should be stopped in the event of a hypersensitive reaction.
Acute Asthma Symptoms or Deteriorating Disease
Acute exacerbations or symptoms of asthma should not be treated with FASENRA. FASENRA should not be used to treat status asthmaticus or acute bronchospasm. After starting FASENRA medication, patients should consult a doctor if their asthma worsens or is still uncontrolled.
Reduction of Corticosteroid Dosage
Once FASENRA medication has begun, do not stop taking systemic or inhaled corticosteroids suddenly. If necessary, moderate dose reductions of corticosteroids should be carried out under a doctor's close supervision. Reducing the dosage of corticosteroids may reveal diseases that were previously repressed by systemic corticosteroid therapy and/or cause systemic withdrawal symptoms.
Parasitic (Helminth) Infection
The immune system's reaction to certain helminth infections may involve eosinophils. Clinical trial participation was restricted to patients with known helminth infections. FASENRA may or may not affect a patient's ability to fight off helminth infections. Prior to starting FASENRA therapy, treat individuals who already have helminth infections. Patients should stop using FASENRA until the infection goes away if they are infected while on the medication and do not improve with anti-helminth therapy.
Use In Specific Populations
Pregnancy
Monoclonal antibodies, like benralizumab, are transferred across the placenta in the third trimester of pregnancy, the fetus may be more susceptible to adverse consequences during this time. In a cynomolgus monkey prenatal and postnatal development study, intravenous (IV) benralizumab administration during pregnancy at doses that resulted in exposures up to roughly 310 times the exposure at the maximum recommended human dose (MRHD) of 30 mg SC did not cause any fetal harm. The background risk of significant birth abnormalities and miscarriage in clinically recognized pregnancies is estimated to be between 2% and 4% and 15% and 20%, respectively, in the general population of the United States.
Lactation
The effects of local exposure in the gastrointestinal tract and maybe limited systemic exposure in the newborn remain unknown if benralizumab is incorporated into human milk. Together with the mother's clinical requirement for benralizumab and any possible negative effects of benralizumab or the underlying maternal condition on the breastfed infant, the developmental and health advantages of breastfeeding should be taken into account.
Geriatric Use
In benralizumab clinical trials, 13% (n=320) of the patients were 65 years of age or older, and 0.4% (n=9) were 75 years of age or older. Although other documented clinical experience has not found differences in responses between the elderly and younger patients, it is impossible to rule out the possibility that some older patients are more sensitive than others. Overall, no differences in safety or effectiveness were noted between these patients and younger patients.
Renal and Hepatic Impairment Considerations for Benralizumab
Renal Impairment:
Currently, there are no formal clinical studies specifically examining the impact of renal impairment on the pharmacokinetics of benralizumab. However, population pharmacokinetic analyses indicate that the clearance of benralizumab is similar in individuals with creatinine clearance values ranging from 30 to 80 mL/min compared to those with normal renal function. Data on patients with creatinine clearance below 30 mL/min are limited, but it is important to note that benralizumab is not primarily cleared through the kidneys.
Hepatic Impairment:
Similarly, no formal studies have been conducted to assess the effects of hepatic impairment on benralizumab. As IgG monoclonal antibodies are not predominantly cleared via the hepatic pathway, changes in liver function are not anticipated to significantly affect the clearance of benralizumab. Population pharmacokinetic analyses have shown that baseline hepatic function biomarkers, including ALT, AST, and bilirubin levels, do not have a clinically relevant impact on the drug's clearance.
Drug-Drug Interactions
To date, no formal studies have been performed to evaluate drug-drug interactions involving benralizumab. The drug's clearance does not involve cytochrome P450 enzymes, efflux pumps, or protein-binding mechanisms. Additionally, there is no evidence of IL-5Rα expression on hepatocytes, and eosinophil depletion does not lead to chronic systemic changes in proinflammatory cytokines. Therefore, it is not expected that benralizumab will affect the pharmacokinetics of co-administered medications. Population analyses have shown that commonly co-administered drugs do not influence the clearance of benralizumab in patients with asthma.
Overdosage
Clinical trials have administered doses of benralizumab up to 200 mg subcutaneously to patients with eosinophilic diseases without observing any dose-related toxicities. In the event of an overdose, there is no specific antidote for benralizumab. Patients should receive supportive care and appropriate monitoring as necessary.21
CONCLUSION
The comprehensive review of benralizumab highlights its significant role in managing severe eosinophilic asthma, particularly for patients inadequately controlled by standard therapies. The thesis of the text emphasizes the importance of benralizumab as a targeted biologic therapy that directly addresses the underlying eosinophilic inflammation associated with asthma. Key points discussed include the drug's FDA approvals, its mechanism of action as an IL-5 receptor antagonist, and its favorable pharmacokinetic and pharmacodynamic profiles. Additionally, the advantages of benralizumab over mepolizumab in reducing exacerbations and improving lung function were noted. While the medication presents benefits, it is also crucial to consider potential adverse effects and contraindications. The review underscores the need for ongoing patient assessment to ensure optimal therapeutic outcomes. Overall, benralizumab represents a promising advancement in the treatment arsenal for eosinophilic asthma, offering hope for improved management of this challenging condition. Future research and clinical experience will further elucidate its long-term efficacy and safety in diverse patient populations.
REFRENCES
Dr. M. Govardhan*, Shaik Rizwana, Alefiya Kotawala, A Comprehensive Review on Drug Profile of Benralizumab, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 3, 783-788. https://doi.org/10.5281/zenodo.15000067
10.5281/zenodo.15000067
