Subcutaneous C1 Esterase Inhibitor (Human) Approved for Prevention of Hereditary Angioedema Attacks

The approval of a C1 Esterase Inhibitor (Human) by the US Food and Drug Administration (FDA) for the prevention of attacks of hereditary angioedema could be a boon to several adolescent and adult patients affected by the rare disease. Hereditary angioedema is a rare genetic disorder in which the patient suffers from attacks of swelling of the tissues just below the skin and mucous membranes in several parts of the body including the face, abdomen and limbs. The number of attacks, the severity of the attacks and the sites affected vary from person to person. The attacks can occur spontaneously, or can be triggered by conditions like stress, surgery or infection.

Swelling around abdominal organs can result in pain, vomiting and diarrhea. Swelling of the face causes temporary disfigurement. If the tissues of the throat (larynx) are involved, breathing can get affected. The condition can therefore be life-threatening.

The affected individuals lack the functional form of a protein called C1-esterase inhibitor (C1-INH). C1-INH controls inflammation mediated by chemicals which constitute the ‘complement system’. In the absence of the protein, the inflammatory process goes unchecked, resulting in seepage of fluid from the blood vessels into the surrounding tissues and swelling of various tissues. The disease may be inherited from parents or may occur due to a new genetic mutation in the baby.

There are three types of hereditary angioedema, types 1, 2 and 3. Type 1 occurs due to deficient C1-INH. In type 2 hereditary angioedema, the C1-INH is present but dysfunctional C1-INH. The C1-INH in type 3 disease is normal, and the exact cause of the condition is not known.

Attacks of hereditary angioedema are treated with special drugs like recombinant human C1-INH, ecallantide and icatibant which arrest the inflammatory process. Drugs like danazole have been used for the prevention of hereditary angioedema. An intravenous C1-esterase inhibitor is also available but may be more inconvenient to use as compared to a subcutaneous preparation.

The recent approval of the subcutaneous C1 Esterase Inhibitor (Human) for the prevention of hereditary angioedema attacks comes following its successful use in the Phase III COMPACT trial. In this trial, the treatment was tested in patients with type 1 or type 2 hereditary angioedema between the ages of 12 and 72 years. Out of the 90 patients included in the study, some received the injection twice a week in doses of 40 IU/kg or 60 IU/kg for 16 weeks, while others received a placebo. The study concluded that:

• Patients in the group that received the medication experienced a considerable reduction in the number of attacks of hereditary angioedema as compared to those who received only placebo.
• The subcutaneous injections restored the level of C1-INH to more than 40%
• Adverse effects included allergic reactions, nasal and throat swelling and dizziness

The medication should not be used in patients who had previously suffered from serious allergic reactions with a C1-INH preparation or its inactive ingredients. In addition, it cannot be used to treat the attacks.

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References:

1. FDA approves first subcutaneous C1 Esterase Inhibitor to treat rare genetic disease - (https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm564332.htm)
2. Longhurst H et al. Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor. N Engl J Med 2017; 376:1131-1140 DOI: 10.1056/NEJMoa1613627

Source-Medindia