Recombinant human C1 esterase inhibitor for the treatment of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE)

Abstract

The lack of C1 inhibitor function that results in excessive production of bradykinin causing the angioedema seen in hereditary angioedema (HAE) is well established. Several drugs have been developed to treat and prevent attacks in patients suffering from HAE due to C1 inhibitor deficiency (C1-INH-HAE). Plasma-derived C1INH has been used to replace the deficiency of C1 inhibitor (C1INH) and has been approved for both treatment of attacks and for prophylactic therapy to prevent attacks. Plasma kallikrein inhibitor (ecallantide) and bradykinin receptor antagonist (icatibant) are both effective for treatment of acute attacks, but their short half-life limits the use for prophylaxis. Androgens, in particular danazol, are effective for long-term prophylaxis, but adverse event profile can limit its use. Recombinant C1 inhibitor derived from transgenic rabbits has recently been approved for use in treatment of C1-INH-HAE attacks and is effective and appears safe with minimal adverse event profile.

Keywords:

• C1 inhibitor
• C1-esterase inhibitor
• hereditary angioedema
• recombinant
• recombinant C1 inhibitor
• treatment

Financial & competing interests disclosure

Craig performs research for Biocryst, CSL Behring, Dyax, Shire and Pharming. He speaks for CSL Behring, Shire and Dyax. He consults for CSL Behring and Biocryst. He has received educational grants from CSL Behring, Dyax and Shire. 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Recombinant C1 esterase inhibitor is indicated for acute attacks in adult and adolescent patients with hereditary angioedema.

• Production from transgenic rabbits increases the reliability of production and eliminates the chance of blood-borne infections making it a competitive option for pdCINH.

• The benefit for long- and short-term prophylaxis has not been established yet.

• Most common adverse reactions were headache, nausea and diarrhea. Only serious adverse reaction was an anaphylactic reaction during the Phase I study in a subject who failed to admit that he was allergic to rabbits. Otherwise, adverse events are unlikely. The main adverse events are associated with the need to inject intravenously.

• Reassuring immunosafety profile of rhC1INH has been established.

• It is contraindicated in patients allergic to rabbits and in patients with history of anaphylaxis to C1 esterase inhibitor preparations.

• Dosing by weight should allow the use of rhC1-INH in children; however, this will be off label use.

Notes