From the FDA Drug Label
The kallikrein-kinin system is a complex proteolytic cascade involved in the initiation of both inflammatory and coagulation pathways One critical aspect of this pathway is the conversion of High Molecular Weight (HMW) kininogen to bradykinin by the protease plasma kallikrein. KALBITOR is a potent (Ki = 25 pM), selective, reversible inhibitor of plasma kallikrein. By directly inhibiting plasma kallikrein, KALBITOR reduces the conversion of HMW kininogen to bradykinin and thereby treats symptoms of the disease during acute episodic attacks of HAE.
Kallikrein is a protease that plays a critical role in the kallikrein-kinin system, which is involved in the initiation of both inflammatory and coagulation pathways.
- The drug KALBITOR (ecallantide) is a potent, selective, and reversible inhibitor of plasma kallikrein.
- By inhibiting plasma kallikrein, KALBITOR reduces the conversion of HMW kininogen to bradykinin, thereby treating symptoms of Hereditary Angioedema (HAE) during acute episodic attacks 1.
From the Research
Kallikrein inhibitors, such as ecallantide, are the most effective treatment for acute attacks of hereditary angioedema, with a significant reduction in symptom severity and improvement in quality of life 2.
Kallikrein Overview
Kallikrein is a group of serine proteases that play important roles in various physiological processes, particularly in the kallikrein-kinin system that regulates blood pressure, inflammation, and pain responses. There are two main types: plasma kallikrein, which circulates in the blood, and tissue kallikrein, found in organs like the kidneys, pancreas, and salivary glands.
Kallikrein Inhibitors
Kallikrein inhibitors, such as ecallantide, are used therapeutically to treat hereditary angioedema attacks. Ecallantide is a novel, specific, and potent inhibitor of plasma kallikrein that has been approved for the treatment of acute attacks of hereditary angioedema in patients aged 16 years and older 3. The recommended dose is 30 mg given as three separate subcutaneous injections 2.
Clinical Evidence
Clinical trials have demonstrated the efficacy and safety of ecallantide in treating acute HAE episodes. For example, a phase III clinical trial found that ecallantide significantly improved symptom severity and quality of life in patients with acute HAE attacks compared to placebo 4. Another study found that ecallantide was well tolerated and effective in reducing symptom severity in patients with HAE 5.
Treatment Considerations
When developing individualized HAE management plans, patient-specific and drug-specific factors should be considered. Optimization of HAE therapy will require further integration of new therapies into the current treatment paradigm 6.
Key Points
- Kallikrein inhibitors, such as ecallantide, are effective in treating acute attacks of hereditary angioedema.
- Ecallantide is a novel, specific, and potent inhibitor of plasma kallikrein.
- The recommended dose of ecallantide is 30 mg given as three separate subcutaneous injections.
- Clinical trials have demonstrated the efficacy and safety of ecallantide in treating acute HAE episodes.