Hereditary Angioedema (HAE)


Kalbitor® is a plasma kallikrein inhibitor indicated for treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years of age and older.1

Mechanism of Action and Use of Kalbitor

HAE occurs when a mutation in the gene that codes for C1-esterase inhibitor (C1-INH) protein results in deficient or absent C1-INH activity and low levels of C4. The consequence is unregulated activation of the complement and intrinsic (contact system) cascades. In addition, C1-INH is a major inhibitor of the kallikrein-kinin system, which plays an important role in the initiation of both inflammatory and coagulation pathways. Kallikrein mediates a critical step in inflammation by converting kininogen to bradykinin. Kalbitor selectively and reversibly inhibits plasma kallikrein by blocking its binding site, thereby halting the unregulated conversion of kininogen to bradykinin and relieving symptoms during an acute attack of HAE.1

Kalbitor is a clear, colorless liquid that is administered subcutaneously in 3 injected doses, each containing 1 mL (10 mg) of Kalbitor, for a total dose of 30 mg. Kalbitor should be administered only by a professional, and appropriate medical support should be available to manage anaphylaxis and HAE. If an attack persists, an additional dose of 30 mg may be administered within a 24-hour period.1 

Get full prescribing information for Kalbitor at MPR

Kalbitor in Clinical Trials

The safety and efficacy of Kalbitor were demonstrated in 2 randomized, double-blind, placebo-controlled trials (EDEMA4 and EDEMA3). Patients were allowed to participate in both trials, for a total of 143 unique patients. Patients having HAE attacks at any location with at least 1 moderate or severe symptom were treated with the subcutaneous administration of 30 mg of Kalbitor or placebo. Results were scored with the Mean Symptom Complex Severity (MSCS) score and the Treatment Outcome Score (TOS). EDEMA3 differed from EDEMA 4 mainly in the order of the prespecified efficacy endpoints. In EDEMA4, the primary endpoint was the change from baseline in the MSCS score at 4 hours, and a key secondary endpoint was the TOS at 4 hours. The mean decrease in the MSCS score (on a scale of 0 to 3) at 4 hours was -0.8 with Kalbitor vs -0.4 with placebo (P=0.01). The TOS is a categorical scale and was also significantly improved at 4 hours in the patients who received Kalbitor vs those who received placebo. EDEMA 3, which mirrored the statistically significant findings of EDEMA4, demonstrated that 14% of patients in the Kalbitor group required additional intervention for unresolved symptoms vs 36% in the placebo group.1

Safety and Efficacy of Kalbitor

The most common adverse reactions were headache, nausea, diarrhea, pyrexia, injection site reactions, and nasopharyngitis. Anaphylaxis has been reported after the administration of Kalbitor; therefore, it is essential that this drug be administered only by a healthcare professional.1

Immunogenic responses to Kalbitor have been documented, and rates of seroconversion are proportional to the duration of exposure. Seroconversion occurs in approximately 20% of patients with the production of anti-ecallantide antibodies, although the presence of neutralizing antibodies is not associated with decreased efficacy. It appears that the most important implication of seroconversion is an increased risk for the development of hypersensitivity reactions. The long-term effects of antibodies to Kalbitor are not known.

According to the pharmacovigilance database, Kalbitor is not associated with a risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. No data are available regarding the presence of ecallantide in human breast milk and its potential effects on breastfed infants. Also, no data are available for the use of Kalbitor in children younger than 12 years.1

Reference

1. KALBITOR® (ecallantide) label. Prescribing information. Takeda. Revised December 2020.

Reviewed by Hasan Avcu, MD, on 6/27/2022.

READ MORE ON HAE