What is the recommended dosage and treatment protocol for benralizumab (anti-interleukin-5 receptor alpha subunit monoclonal antibody) in patients with severe asthma or hypereosinophilic syndrome who have not responded to standard therapies, as investigated in the SHAMAL trial?

Benralizumab Dosing and Treatment Protocol for Severe Asthma and Hypereosinophilic Syndrome

For patients with severe eosinophilic asthma, benralizumab should be administered at a dose of 30 mg subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks thereafter, as demonstrated in the SHAMAL trial and other pivotal studies. 1, 2

Approved Dosing Protocol for Benralizumab

• The FDA-approved dosing regimen for benralizumab is 30 mg administered subcutaneously every 4 weeks for the first three doses, followed by once every 8 weeks maintenance dosing 1
• This dosing protocol has been consistently used across clinical trials including SIROCCO, CALIMA, and most recently SHAMAL 3, 4, 2
• The medication is available as a prefilled syringe or autoinjector containing 30 mg/mL solution for subcutaneous injection 1

Efficacy in Severe Asthma

• Benralizumab works by binding to the alpha subunit of the interleukin-5 receptor (IL-5Rα) on eosinophils, leading to antibody-dependent cell-mediated cytotoxicity (ADCC) and rapid depletion of eosinophils 1, 5
• Treatment results in reduction of blood eosinophil counts to a median absolute count of 0 cells/μL, with this effect observed as early as 4 weeks after treatment initiation 1
• The SHAMAL trial demonstrated that patients with severe eosinophilic asthma who are well-controlled on benralizumab can successfully reduce their inhaled corticosteroid (ICS) dose while maintaining asthma control 2
• In the SHAMAL trial, 92% of patients were able to reduce their ICS-formoterol dose, with 61% reducing to as-needed use only, and 96% maintained these reductions through week 48 2

Patient Selection Criteria

• Benralizumab is most effective in patients with:
  • Blood eosinophil counts ≥300 cells/μL 4, 3
  • History of frequent exacerbations (two or more in the previous year) despite high-dose ICS plus LABA therapy 4, 3
  • The greatest treatment effect is observed in patients with both high blood eosinophil counts and more frequent exacerbations 4

Application in Hypereosinophilic Syndrome

• For hypereosinophilic disorders, benralizumab has shown significant lowering of eosinophil counts in both serum and tissue 6
• A phase-2 study in hypereosinophilic syndrome demonstrated 74% of patients having sustained response at 48 weeks with no adverse events limiting treatment 6
• The same dosing regimen used for asthma (30 mg subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks) has been applied in these studies 7

Monitoring and Safety Considerations

• Monitor blood eosinophil counts to confirm treatment response, with significant reduction typically seen within 24 hours and maintained throughout treatment 1
• Common adverse events include worsening asthma (13% vs 19% for placebo), nasopharyngitis (12%), and injection site reactions (erythema in up to 35% of patients) 1, 6
• The SHAMAL trial reported similar rates of adverse events between groups reducing ICS and those maintaining ICS doses, supporting the safety of ICS reduction while on benralizumab 2
• Therapeutic drug monitoring is recommended when using benralizumab according to the European Respiratory Society 7

Important Clinical Considerations

• Benralizumab is not currently recommended as first-line therapy for eosinophilic esophagitis (EoE) according to the American Gastroenterological Association, which suggests using it only in the context of clinical trials 6
• However, case reports have shown complete resolution of dysphagia symptoms and histological evidence of deep remission in patients with both eosinophilic asthma and EoE treated with benralizumab 6
• The MESSINA phase 3 trial is evaluating benralizumab in EoE patients, which may provide further evidence for its use in this condition 6

Practical Application Based on SHAMAL Trial

• The SHAMAL trial specifically demonstrated that patients with well-controlled severe eosinophilic asthma on benralizumab can safely reduce their ICS dose 2
• 91% of patients in the reduction group had zero exacerbations during tapering, suggesting that the anti-inflammatory effects of benralizumab may reduce the need for high-dose ICS 2
• This supports a treatment approach where clinicians can consider ICS dose reduction after establishing good asthma control with benralizumab 2