General Information

Haegarda is a plasma-derived concentrate of C1 Esterase Inhibitor (Human). HAE patients have absence or low levels of endogenous or functional C1-INH.

Haegarda is specifically indicated for routine prophylaxis to prevent Hereditary Angioedema (HAE) attacks in adolescent and adult patients. The FDA expanded the label in September of 2020 to include the use of Haegarda in patients six years of age and older.

Haegarda is supplied as a freeze-dried powder for reconstitution for subcutaneous administration. Administer 60 International Units per kg body weight twice weekly (every 3 or 4 days). Reconstitute Haegarda prior to use using Sterile Water for Injection, USP. Use a silicone-free syringe for reconstitution and administration.  Administer at room temperature within 8 hours after reconstitution.

Mechanism of Action

C1-INH is a normal constituent of human plasma and belongs to the group of serine protease inhibitors (serpins) that includes antithrombin III, alpha1-protease inhibitor, alpha2-antiplasmin, and heparin cofactor II. As with the other inhibitors in this group, C1-INH has an important inhibiting potential on several of the major human cascade systems, including the complement, fibrinolytic and coagulation systems. Regulation of these systems is performed through the formation of complexes between the protease and the inhibitor, resulting in inactivation of both and consumption of the C1-INH. 

C1-INH, which is usually activated during the inflammatory process, inactivates its substrate by covalently binding to the reactive site. C1-INH is the only known inhibitor for the C1r and C1s subcomponents of complement component 1 (C1), coagulation factor XIIa, and plasma kallikrein. Additionally, C1-INH is the main inhibitor for coagulation factor XIa of the intrinsic coagulation cascade.

HAE patients have absence or low levels of endogenous or functional C1-INH. Although the events that cause attacks of angioedema in HAE patients are not well defined, it has been postulated that increased vascular permeability and the clinical manifestation of HAE attacks may be primarily mediated through contact system activation. Suppression of contact system activation by C1-INH through the inactivation of plasma kallikrein and factor XIIa is thought to modulate this vascular permeability by preventing the generation of bradykinin. Administration of HAEGARDA replaces the missing or malfunctioning C1-INH protein in patients with HAE. 

Side Effects

Adverse effects associated with the use of Haegarda may include, but are not limited to, the following:

• injection site reaction
• hypersensitivity
• nasopharyngitis
• dizziness

Clinical Trial Results

The FDA approval was based on the Phase III COMPACT (Clinical Studies for Optimal Management in Preventing Angioedema with low-volume subcutaneous C1-inhibitor replacement Therapy) trial, which showed that at the approved dose of 60 IU/kg, Haegarda reduced the median number of HAE attacks by 95 percent relative to placebo. Use of rescue medication was reduced by greater than 99 percent versus placebo.