Benralizumab
Introduction to Benralizumab
Benralizumab (trade name: Fasenra) is a humanized monoclonal antibody that targets the interleukin-5 receptor alpha (IL-5Rα) expressed on eosinophils. Approved by the FDA in 2017, benralizumab is used as an add-on maintenance treatment for severe eosinophilic asthma in patients aged 12 years and older.
As a biologic therapy, benralizumab represents an important advancement in the management of severe asthma, offering a unique mechanism of action that rapidly and nearly completely depletes eosinophils, a key cell type involved in the pathogenesis of eosinophilic asthma.
Mechanism of Action
Benralizumab works through a distinct mechanism compared to other anti-IL-5 therapies:
- Selective binding to IL-5Rα on eosinophils and basophils
- Recruitment of natural killer (NK) cells via its afucosylated Fc domain
- Induction of antibody-dependent cell-mediated cytotoxicity (ADCC) of eosinophils and basophils
- Rapid and nearly complete depletion of eosinophils in blood and tissues
- Inhibition of eosinophil maturation in bone marrow
This unique mechanism results in a more profound and sustained reduction in eosinophils compared to other IL-5 targeted therapies, potentially offering advantages in terms of efficacy and dosing frequency.
Indications
Benralizumab is indicated as an add-on maintenance treatment for patients aged 12 years and older with severe eosinophilic asthma. Key criteria for considering benralizumab therapy include:
- Confirmed diagnosis of severe asthma
- Blood eosinophil count ≥ 300 cells/μL
- Inadequate asthma control despite high-dose inhaled corticosteroids and an additional controller medication
- History of frequent exacerbations requiring systemic corticosteroids
It's important to note that benralizumab is not approved for the treatment of other eosinophilic conditions or for acute bronchospasm or status asthmaticus.
Dosage and Administration
Benralizumab is administered as a subcutaneous injection. The recommended dosage regimen is:
- 30 mg every 4 weeks for the first 3 doses
- Then 30 mg every 8 weeks thereafter
Key points about administration:
- Administered by a healthcare professional
- Injection sites include upper arm, thigh, or abdomen
- No weight-based dosing adjustment required
- Available as a single-dose prefilled syringe or autoinjector
The extended dosing interval (every 8 weeks) after the initial loading doses is a unique feature of benralizumab, potentially improving treatment adherence and reducing the burden on patients and healthcare systems.
Efficacy
Clinical trials have demonstrated the efficacy of benralizumab in patients with severe eosinophilic asthma. Key findings include:
- Significant reduction in annual asthma exacerbation rate (up to 51% reduction compared to placebo)
- Improvement in lung function (FEV1)
- Reduction in oral corticosteroid use in steroid-dependent patients
- Improvement in asthma symptoms and quality of life scores
- Rapid and sustained reduction in blood eosinophil counts (within 24 hours of first dose)
Notable efficacy features of benralizumab include:
- Rapid onset of action, with improvements observed as early as 4 weeks after initiation
- Sustained efficacy over long-term treatment (up to 2 years in extension studies)
- Potential for improved outcomes in patients with higher baseline blood eosinophil counts (≥ 300 cells/μL)
Safety Profile
Benralizumab has demonstrated a favorable safety profile in clinical trials and post-marketing surveillance. Key safety considerations include:
- Common side effects:
- Headache
- Pharyngitis
- Injection site reactions
- Hypersensitivity reactions
- Serious adverse events (rare):
- Anaphylaxis
- Opportunistic infections (theoretical risk due to eosinophil depletion)
Additional safety considerations:
- Low immunogenicity rates (anti-drug antibodies reported in about 13% of patients, but generally not affecting efficacy or safety)
- No rebound eosinophilia observed upon treatment discontinuation
- No increased risk of malignancy or cardiovascular events observed in long-term studies
Patients should be counseled about the potential for hypersensitivity reactions and the importance of reporting any new or worsening symptoms promptly.
Pediatric Considerations
Benralizumab is approved for use in patients aged 12 years and older, making it an important treatment option for adolescents with severe eosinophilic asthma. Key pediatric considerations include:
- Efficacy and safety in adolescents (12-17 years) consistent with adult population
- No dose adjustment required based on age or body weight
- Potential for improved adherence due to less frequent dosing schedule (every 8 weeks)
- Limited data available for long-term safety and efficacy in pediatric populations
- Ongoing studies evaluating use in younger children (6-11 years)
Pediatricians should consider benralizumab for adolescents with severe eosinophilic asthma who meet the following criteria:
- Inadequate control with high-dose inhaled corticosteroids and additional controller medications
- Blood eosinophil count ≥ 300 cells/μL
- History of frequent exacerbations or dependence on oral corticosteroids
When initiating benralizumab in adolescents, close monitoring and patient education are essential to ensure optimal outcomes and adherence to the treatment regimen.
