General Information

Cinryze is a C1 inhibitor derived from human plasma. C1 inhibitor is a normal constituent of human blood and is one of the serine proteinase inhibitors (serpins). The primary function of C1 inhibitor is to regulate the activation of the complement and intrinsic coagulation (contact system) pathway. C1 inhibitor also regulates the fibrinolytic system. HAE patients have low levels of endogenous or functional C1 inhibitor.

Cinryze is specifically indicated for routine prophylaxis against angioedema attacks in adolescent and adult patients with Hereditary Angioedema (HAE).

Cinryze is supplied as a powder to be reconstituted with 5 mL sterile water for intravenous injection. The recommended initial dose of the drug is 1 mL/min for 10 minutes. If this is well tolerated, a dose of 1,000 units Cinryze can be administered every 3 or 4 days for routine prophylaxis.

Clinical Results

FDA Approval
The FDA approval of Cinryze was based on the results a clinical trial. This randomized, double blind, placebo controlled multi-center cross-over study enrolled 24 subjects with HAE. The subjects were randomized to one of two treatment groups: either Cinryze prophylaxis for 12 weeks followed by 12 weeks of placebo prophylaxis; or randomized to placebo prophylaxis for 12 weeks followed by 12 weeks of Cinryze prophylaxis. The subjects were given blinded injections of Cinryze or placebo every 3 to 4 days, approximately 2 times per week. Twenty-two subjects crossed over into period 2 and were included in the efficacy analysis. Efficacy was based on the number of attacks during the 12 week period while receiving Cinryze as compared to the number of attacks during the placebo treatment period. The subjects in the Cinryze treatment arm had a mean of 6.1 HAE attacks compared to a mean of 12.7 attacks in the placebo group. In addition, subjects in the Cinryze arm had a 66% reduction in days of swelling (p<0.0001), and decreases in the average severity of attacks (p=0.0006) and the average duration of attacks (p=0.0023).

Side Effects

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

• Viral upper respiratory tract infection
• Sinusitis
• Rash
• Headache
• Respiratory tract infections

Mechanism of Action

Cinryze is a C1 inhibitor derived from human plasma. C1 inhibitor is a normal constituent of human blood and is one of the serine proteinase inhibitors (serpins). The primary function of C1 inhibitor is to regulate the activation of the complement and intrinsic coagulation (contact system) pathway. C1 inhibitor also regulates the fibrinolytic system. Regulation of these systems is performed through the formation of complexes between the proteinase and the inhibitor, resulting in inactivation of both and consumption of the C1 inhibitor. HAE patients have low levels of endogenous or functional C1 inhibitor.

Literature References

Bork K, Staubach P, Hardt J Treatment of skin swellings with C1-inhibitor concentrate in patients with hereditary angio-oedema. Allergy 2008 Jun;63(6):751-7

Farkas H, Jakab L, Temesszentandrási G, Visy B, Harmat G, Füst G, Széplaki G, Fekete B, Karádi I, Varga L Hereditary angioedema: a decade of human C1-inhibitor concentrate therapy. The Journal of allergy and clinical immunology 2007 Oct;120(4):941-7

Bork K, Barnstedt SE Treatment of 193 episodes of laryngeal edema with C1 inhibitor concentrate in patients with hereditary angioedema. Archives Internal Medicine 2001 Mar 12;161(5):714-8

Kunschak M, Engl W, Maritsch F, Rosen FS, Eder G, Zerlauth G, Schwarz HP A randomized, controlled trial to study the efficacy and safety of C1 inhibitor concentrate in treating hereditary angioedema. Transfusion 1998 Jun;38(6):540-9

Additional Information

For additional information regarding Cinryze or hereditary angioedema, please visit the Cinryze web page.