OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Emicizumab – Hemlibra®

DRUG CLASS

Hematologic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 20 October 2018

• Zimmerman HJ. Drugs used to treat rheumatic and musculospastic disease. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 517-54.

  (Expert review of hepatotoxicity published in 1999, well before the availability of most monoclonal antibody therapies).
• 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; mentions rituximab and problems of reactivation of hepatitis B, but also states that "the biological immunosuppressants are largely free from hepatotoxicity, with the exception of the TNF alpha antagonists"; eculizumab is not specifically mentioned).
• 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: ”No clinically significant changes in laboratory parameters were observed during treatment with emicizumab” and there were no instances of clinically apparent liver injury with jaundice).
• Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, Fukazawa N, et al. Factor VIII-mimetic function of humanized bispecific antibody in hemophilia A. N Engl J Med 2016; 374: 2044-53. 27223146. [PubMed: 27223146]

  (Among 18 Japanese patients with severe hemophilia A treated with 0.3, 1.0 or 3.0 mg/kg weekly for 12 weeks, bleeding rates decreased by 90% in all groups and 71-73% of patients had no bleeding episodes and there were no treatment related serious adverse events; no mention of ALT elevations or hepatotoxicity).
• Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, Kasai R, et al. Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors. Blood Adv 2017; 1: 1891-9. 29296836. [PMC free article: PMC5728143] [PubMed: 29296836]

  (Among 14 Japanese patients with severe hemophilia A who participated in a phase 1 trial [Shima 2016] and were continued on emicizumab for up to 33 months, bleeding rates remained low and therapy was “well tolerated” with no treatment related serious adverse events or thromboembolic events; no mention of ALT elevations or hepatotoxicity).
• Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, Santagostino E, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med 2017; 377: 809-18. 28691557. [PubMed: 28691557]

  (Among 109 patients with hemophilia A and factor VIII inhibitors who were treated with weekly injections of emicizumab or placebo, bleeding events were 87% less in emicizumab treated subjects while side effects were similar except for injection site reactions [15% vs 8%] and thrombotic microangiopathy [2% vs none]; no mention of ALT elevations or hepatotoxicity).
• Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, Schmitt C, et al. Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med 2018; 379: 811-22. 30157389. [PubMed: 30157389]

  (Among 152 patients with hemophilia A without factor VIII inhibitors who were treated with weekly or biweekly injections of emicizumab or no treatment, bleeding events were 958% less with emicizumab prophylaxis while side effects were similar except for injection site reactions, and there were on instances of thrombotic microangiopathy and no ALT elevations or hepatotoxicity).
• Franchini M, Mannucci PM. Non-factor replacement therapy for haemophilia: a current update. Blood Transfus 2018; 16: 1-5. 29517971. [PMC free article: PMC6125230] [PubMed: 29517971]

  (Review of efficacy and safety of non-factor VIII replacement therapy for hemophilia including use of emicizumab in patients with and without inhibitors; no mention of ALT elevations or hepatotoxicity).
• Scott LJ, Kim ES. Emicizumab-kxwh: first global approval. Drugs 2018; 78: 269-74. 29357074. [PubMed: 29357074]

  (Review of the development, mechanism of action, pharmacology, clinical efficacy and safety of emicizumab shortly after its approval for use in hemophilia A in the US; discusses adverse events of thromboembolism but does not mention ALT elevations or hepatotoxicity).