Human plasma-derived C1 esterase inhibitor for on-demand or prophylaxis treatment of patients with hereditary angioedema: intravenous and subcutaneous formulations

ABSTRACT

Introduction: Hereditary angioedema with C1 inhibitor (C1-INH) deficiency (C1-INH-HAE) is a rare disease in which patients have debilitating, unpredictable swelling attacks. Treatment approaches include prophylaxis therapies to prevent future attacks and on-demand therapies that reduce the duration and severity of an attack.

Areas covered: This review summarizes the characteristics and efficacy and safety profiles of two formulations of human plasma-derived C1-INH concentrates, intravenous BERINERT® for on-demand treatment of attacks and subcutaneous HAEGARDA® for routine prophylaxis of attacks.

Expert opinion: Intravenous C1-INH concentrates have long been used in the treatment of patients with C1-INH-HAE, and the recent approval of the subcutaneous formulation is a major advancement in prophylaxis therapy. Subcutaneous administration provides more stable and sustained trough C1-INH levels compared with intravenous administration. Pharmacokinetic modeling revealed a close relationship between trough functional C1-INH activity levels and the patient’s risk of experiencing an angioedema attack. The approved dose of subcutaneous C1-INH (60 IU/kg) provides clinically relevant and protective plasma levels of C1-INH throughout the dosing interval. The pharmacokinetic profile of the intravenous formulation consists of a rapid increase and high peak plasma levels of C1-INH, making intravenous administration well suited for the on-demand treatment of acute attacks.

KEYWORDS:

• C1 esterase inhibitor
• hereditary angioedema

Declaration of interest

JA Bernstein is a consultant, speaker, and principal investigator for CSL Behring, Shire, and Pharming and a consultant and principal investigator for Biocryst. Medical writing assistance was provided by Scott Newcomer, MS, CMPP™ of Davenport Scientific Services. Funding for medical writing support provided by an educational grant from CSL Behring. Employees of CSL Behring were not involved in the conception or writing of the manuscript, but reviewed a draft of the manuscript before submission. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. A reviewer on this manuscript has disclosed receiving travel grants from CSL Behring, Shire and Pharming and has participated in clinicaltrials/registries for BioCryst, CSL Behring, Pharming and Shire.

Additional information

Funding

Medical writing support funded by CSL Behring.