Conestat alfa: an orphan drug for the treatment of hereditary angioedema

ABSTRACT

Introduction: Hereditary angioedema due to C1 inhibitor (C1-INH) deficiency (C1-INH-HAE) is a rare disorder, characterized by episodes of cutaneous and/or mucosal edema with unpredictable location and clinical severity. It belongs to the bradykinin-mediated angioedemas requiring specific treatment. Excessive bradykinin release, the culprit behind the onset of symptoms, can be prevented by the supplementation of deficient proteins or by the inhibition of kallikrein, as well as by blocking the effects of bradykinin on its receptor with the administration of a bradykinin B2 receptor antagonist.

Areas covered: Human plasma-derived C1-INH has been used for decades to replenish the deficient protein and lately, recombinant human C1-INH (rhC1-INH), conestat alfa (Ruconest) has become available for this purpose. Three randomized, double-blind, placebo-controlled trials, one open label, and three open-label extension studies have demonstrated the safety and efficacy of rhC1-INH administered for the management of edematous episodes occurring in adolescent patients, or adult patients with C1-INH-HAE regardless of the location of edema and with repeated dosing. Moreover, a pilot study has shown rhC1-INH promising also for the prophylaxis of edematous attacks.

Expert opinion: The introduction of rhC1-INH has expanded the therapeutic options available for the management of C1-INH-HAE, and advanced the individualized therapy for patients with this disease.

KEYWORDS:

• Hereditary angioedema
• C1-inhibitor deficiency
• recombinant human C1-inhibitor
• conestat alfa
• treatment
• orphan drug

Acknowledgement

The author wishes to thank the patients for participating in the clinical studies, and thereby contributing to the efforts to make the new therapeutic agents available in routine clinical practice. Further, the invaluable comments of Aurag Relan MD (Pharming Group NV) and the assistance of Nora Veszeli PhD student (3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary) in compiling the list of literature references is hereby acknowledged with sincere thanks.

Declaration of interest

H Farkas has received consultancy/speaker fees and honoraria from Shire Human Genetic Therapies Inc, Swedish Orphan Biovitrum, CSL Behring and Biocryst Pharmaceuticals Inc. She has 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.