What is HAE?
Between 8,000 and 10,000 people in the U.S. are affected by the most common form of HAE which is caused by an autosomal dominant mutation that decreases C1 inhibitor levels.
Plasma kallikrein plays a major role in the kallikrein-kinin cascade producing bradykinin. Bradykinin is a vasodilator, which increases vascular permeability, activates inflammation and produces pain.
Ecallantide (DX-88, Kalbitor)
Ecallantide (DX-88, Kalbitor) is a subcutaneous kallikrein inhibitor which was approved for treatment of hereditary angioedema (HAE) in patients 16 years of age and older on December 2, 2009.
New therapies for hereditary angioedema (HAE) (click to enlarge the image).
The drug is to be launched in the first quarter of 2010 and see an ex-U.S. partnership in the first half of next year. Kalbitor is the only approved treatment for life-threatening laryngeal attacks.
The drug's short half-life is the main reason for its suitability as a treatment for acute attacks only and not as a preventive therapy.
Kalbitor has a half-life of about two hours, while Cinryze has a half-life of about 56 hours and Berinert has about 22 hours.
FDA Approves Two New Drugs: BioBuzz. TheStreet.com.
The labelling of the drug includes a black-box warning for possible allergic reactions which usually occur within 10 minutes of the injection. This means that the injections will typically be administered in a supervised setting (doctor's office) rather than by the patient at home.
As a condition of the FDA approval, Dyax is required to set up a risk management program to warn patients that Kalbitor can cause severe allergic reactions.
Other treatments of HAE
Cinryze is only approved as a preventive therapy.
Berinert was approved by the FDA in October 2009 for only acute abdominal and facial attacks of the disease. HAE patients can self-administer Berinert C1-INH by IV infusion - FDA, 2012.
Virtually No Relapses After Ecallantide for Acute HAE attacks, despite short half-life. Medscape, 2011.