Recombinant human C1-inhibitor for treatment hereditary angioedema (HAE)

Hereditary angioedema (HAE) results from a genetic deficiency of C1-inhibitor. C1-inhibitor has been produced in glycosylated form in the milk of transgenic rabbits.

New therapies for hereditary angioedema (HAE) (click to enlarge the image).

Angioedema (AE) can be allergic or non-allergic.

There are 5 types of non-allergic angioedema (AE):

- acquired AE
- hereditary AE (HAE)
- ACE-inhibitor induced AE
- idiopathic AE, can occur with chronic urticaria
- pseudoallergic AE, e.g. reaction to NSAIDs

There are 3 types of HAE that are differentiated by C4 and C1-INH levels

- type I HAE - low C4, low C1-INH function, low C1-INH antigen level
- type II HAE - low C4, low C1-INH function, normal C1-INH antigen level
- type III HAE - all normal

Patients with an eligible attack were randomized to a single intravenous dose of recombinant human C1-inhibitor (rhC1INH) or saline.

Therapeutic failure occurred in 59% of the saline group compared with 0% of the 50 U/kg group and 10% of the 100 U/kg group. No postexposure antibody responses against rhC1INH were observed.

Administration of rhC1INH at 100 or 50 U/kg was highly effective as a treatment of acute attacks in patients with HAE. It was also safe and well tolerated.

Treatment of acute HAE attacks

- C1-INH, 20 units/kg, IV infusion
- Icatibant, 30 mg SC, bradykinin B2 receptor antagonist
- Ecallantide, 30 mg SC, kallikrein receptor antagonist

Prophylaxis of HAE attacks

- C1-INH, 1,000 units, IV infusion every 3-4 days
- attenuated androgen, e.g. danocrine 200 mg PO TID


New Directions in the Treatment of Angioedema. Medscape, 2012.

Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema. J Allergy Clin Immunol. 2010 Oct;126(4):821-827.e14.

HAE: annual drug cost alone for prophylactic C1 esterase inhibitor is $450k - nearly $5 mln for every decade of life

Optimal efficacy of C1INH therapy in HAE is achieved at doses ≥50 U/kg, target level ≥0.7 U/ml (70% of normal)

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