Cinryze™ as the first approved C1 inhibitor in the USA for the treatment of hereditary angioedema: approval, efficacy and safety

Abstract

Hereditary angioedema (HAE) is a clinical disorder characterized by a deficiency of C1 esterase inhibitor (C1-INH). HAE has traditionally been divided into two subtypes. Unique among the inherited deficiencies of the complement system, HAE Types I and II are inherited as an autosomal dominant disorder. The generation of an HAE attack is caused by the depletion and/or consumption of C1-inhibitor manifested as subcutaneous or submucosal edema of the upper airway, face, extremities, or gastrointestinal tract. Attacks can be severe and potentially life-threatening, particularly with laryngeal involvement. Despite the availability of C1-INH for the treatment of HAE since the 1980s in Europe and other countries, HAE treatment in the United States was limited to androgen therapy. The human plasma-derived C1 esterase inhibitor (Cinryze™), distributed by Lev Pharmaceuticals, was approved in October 2008 for the prevention of HAE attacks based on the results of a phase III clinical trial. This review aims to describe the history of C1-INH replacement in HAE as well as the pharmacology, efficacy and safety of C1-INH, concentrating on Cinryze as the first approved chronic replacement treatment for the prophylaxis of HAE attacks.

Opinions of Turkish Hereditary Angioedema Patients Regarding the Use of C1 Inhibitor Concentrate in the Treatment of Acute Attacks

“…This finding can explain high satisfaction levels in patient responses. The safety and tolerability studies find that C1-inh concentrate was well tolerated (15,16). The adverse events rate was lower than 5% and the most frequent adverse events including respiratory infections, headache, sinusitis, and rash were characterized as mild (17).…”

Therapy of hereditary angioedema: is it time to focus on a different strategic approach? psychosocial issues and stress management

“…Human plasmaderived concentrate (pd C1-INH Cinryze) was approved in 2008. 16 It is a nano filtered, lyophilized intravenous preparation free of viral and other potential pathogens. Another C1-INH concentrate (Berinert ) is a pasteurized, nano filtered, and lyophilized concentrate derived fro m human plasma for intravenous injection, that received its approval in 2009 for the management of angioedema attacks of the face and abdomen in adult and adolescent patients.…”

Therapeutic complement inhibition in complement-mediated hemolytic anemias: Past, present and future

“…HAE is characterized by uncontrolled bradykinin generation leading to increased vascular permeability, eventually associated with catastrophic episodes of subcutaneous and submucosal edema which may have fatal outcome; the natural history of HAE has been changed by the availability of different C1-INH analogs [165]. The first C1-INH approved for clinical use (second complement inhibitor in general, after eculizumab) is named Cinryze ® (ViroPharma/Baxter), which is a human plasma-derived protein prepared by nanofiltration [166]. More recently, other three formulations of C1-INH became available in the clinic; the first two, like Cinryze, are obtained from human plasma (their names are Berinert and Cetor [165]), whereas the last one is a recombinant C1-INH which has been made available by Salix Pharmaceuticals.…”