OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 05 July 2018

Abbreviations: COPD, chronic obstructive pulmonary disease; IL-5, interleukin-5.

• Reuben A. Hepatotoxicity of immunosuppressive drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2011, pp. 569-91.

  (Review of hepatotoxicity of immunosuppressive agents before the availability of benralizumab; "the biological immuno-suppressants are largely free from hepatotoxicity, with the exception of the TNF alpha antagonists”).
• Barnes PJ. Pulmonary pharmacology. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1031-65.

  (Textbook of pharmacology and therapeutics).
• https://www​.accessdata​.fda.gov/scripts/cder/daf/

  (FDA Drug Approvals website that has product labels [package inserts], letters of approval and full FDA scientific review of the new drug application for safety and efficacy).
• Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, Leiferman KM, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol 2009; 124: 1319-25. e3. [PMC free article: PMC2829669] [PubMed: 19910029]

  (Among 188 patients with hypereosinophilic syndrome seen at 11 referral centers in the US between 2001 and 2006, 55% were male, ages 6 to 85 [median=45] years, most patients responded to corticosteroids and resistant cases often responded to therapy with monoclonal antibody to IL5).
• Gleich GJ, Klion AD, Lee JJ, Weller PF. The consequences of not having eosinophils. Allergy 2013; 68: 829-35. [PMC free article: PMC3915877] [PubMed: 23742015]

  (Review data on patients treated with monoclonal antibody to IL5 for several years failed to show any identifiable, long term adverse effects of inhibition or decrease in eosinophil counts).
• Castro M, Wenzel SE, Bleecker ER, Pizzichini E, Kuna P, Busse WW, Gossage DL, et al. Benralizumab, an anti-interleukin 5 receptor α monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med 2014; 2: 879-90. [PubMed: 25306557]

  (Among 324 adults with uncontrolled eosinophilic asthma treated with benralizumab [2, 20 or 100 mg every 4-8 weeks] vs placebo, rates of exacerbation were reduced with the 100 mg dose of benralizumab compared to placebo, while adverse event rates were similar except for nasopharyngitis and injection site reactions; no mention of ALT elevations or hepatotoxicity).
• Brightling CE, Bleecker ER, Panettieri RA Jr, Bafadhel M, She D, Ward CK, Xu X, 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: 891-901. [PMC free article: PMC5082845] [PubMed: 25208464]

  (Among 101 patients with chronic obstructive lung disease and sputum eosinophilia treated with injections of benralizumab [100 mg every 4-8 weeks] or placebo for 48 weeks, rates of acute exacerbation were similar in the two groups as were rates of adverse events).
• Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, Sproule S, et al.; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β(2)-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016; 388(10056): 2115-27. [PubMed: 27609408]

  (Among 1205 patients with severe uncontrolled asthma treated with benralizumab [30 mg every 4 or 8 weeks] or placebo for 48 weeks, rates of exacerbation were lower with benralizumab compared to placebo and the reduction was most clear in those with preexisting eosinophilia; overall and serious adverse event rates were similar in all groups; no mention of ALT elevations or hepatotoxicity).
• FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, Ferguson GT, et al.; CALIMA study investigators. 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): 2128-41. [PubMed: 27609406]

  (Among 1306 patients with severe, uncontrolled eosinophilic asthma treated with benralizumab [30 mg in two dose regimens] or placebo for 48 weeks, exacerbation rates were lower with benralizumab while adverse event rates were similar).
• Nixon J, Newbold P, Mustelin T, Anderson GP, Kolbeck R. Monoclonal antibody therapy for the treatment of asthma and chronic obstructive pulmonary disease with eosinophilic inflammation. Pharmacol Ther 2017; 169: 57-77. [PubMed: 27773786]

  (Review of the role of eosinophils in asthma and chronic obstructive lung disease and clinical efficacy of monoclonal antibodies to IL5 including reslizumab and mepolizumab).
• Ferguson GT, FitzGerald JM, Bleecker ER, Laviolette M, Bernstein D, LaForce C, Mansfield L, et al.; BISE Study Investigators. Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med 2017; 5: 568-76. [PubMed: 28545978]

  (Among 211 patients with mild-to-moderate asthma treated with benralizumab [30 mg every 4 weeks] or placebo for 12 weeks, improvements in forced expiratory volume and symptoms were minimally better with benralizumab than placebo and adverse event rates were similar).
• Benralizumab (Fasenra) for severe eosinophilic asthma. Med Lett Drugs Ther 2018; 60 (1541): 33-35. [PubMed: 29485975]

  (Concise review of the mechanism of action, clinical efficacy, safety and costs of benralizumab shortly after its approval as therapy of eosinophilic asthma in the US; mentions adverse event rates were similar with benralizumab as placebo and does not mention ALT elevations or hepatotoxicity).