Status: BLA approved in Oct. 2009; marketed in Europe

Organizations involved:

CSL Behring LLC – USA mark.

CSL Behring AG – Manuf.; R&D; Tech.; Europe mark.

CSL Ltd. – parent co.

Cross ref.: See the entry (#113) for recombinant transgenic rabbit-expressed C1-INH (Rhucin) for further information about C1-INH; and the following entry for another plasma-derived C1-esterase inhibitor product.

Description: Berinert P (U.S. trade name not disclosed yet) is a lyophilized (freeze-dried) formulation of complement C1 esterase inhibitor (C1-INH) derived from donated human plasma. The specific C1-esterase inhibitor activity is at least 4.0 U/mg of protein. One U of C1-esterase inhibitor corresponds to the quantity of C1-esterase inhibitor present in 1 mL of fresh, normal plasma.

Nomenclature: C1-esterase inhibitor/CSL [BIO]; Berinert P [TR in Germany, Austria, Switzerland, and several other countries]; 80295-38-1 [CAS RN]; C1INH [SY]; C1-INH [SY]; complement C1 esterase inhibitor, plasma-derived [SY]

Companies.: Berinert P is manufactured and marketed in Europe by CSL Behring AG, a subsidiary of CSL Ltd. CSL Behring currently manufactures and sells C1-INH concentrate in Germany, Austria, Switzerland, and several other countries under the trade name Berinert P.

FDA class: Biologic BLA

Approvals: 20091009; BLA

Indications: [Full text of the "Indications and USAGE” section of the product insert/labeling]:

Berinert is a plasma derived C1 Esterase Inhibitor (Human) indicated for the treatment of acute abdominal or facial attacks of hereditary angioedema (HAE) in

adult and adolescent patients.

Status: On March 6, 2008, CSL Behring submitted a BLA to FDA for approval of its C1-esterase inhibitor for the acute treatment of hereditary angioedema (HAE). The PDUFA date (theoretical approval target decision date) is Sept. 15, 2008, about a month ahead of the date set for an approval decision concerning Cinryze (see entry below). With both products having orphan designation for acute HAE, the first one to receive approval may prevent the other from entering the U.S. market (for 7 years).

On Oct. 9, 2009, FDA approved Berinert, which became the first treatment available in the U.S. for acute abdominal attacks and facial swelling associated with a rare and potentially life-threatening genetic disease called hereditary angioedema (HAE).

On April 17, 2008, CSL filed for approval in Canada for treatment of HAE.

Berinert is marketed in European countries, but has was not approved through the centralized EU/EMEA approval mechanism.

Trials: The BLA submission was based primarily on a completed Phase II/III prospective, double-blind placebo-controlled International Multi-center Prospective Angioedema C1-Inhibitor Trial (I.M.P.A.C.T.) in 124 patients, the largest HAE trial ever, that studied the efficacy of pasteurized C1-INH concentrate. The study enrolled 124 HAE patients with acute, moderate, or severe abdominal or facial attacks. C1-INH concentrate was administered at two different doses and compared to placebo. The main study endpoints were: time to onset of symptom relief from HAE attacks, proportion of subjects with worsening clinical HAE symptoms, and safety. Patients receiving C1-INH concentrate had a median time to symptom relief of 30 minutes, vs. 90 minutes for patients receiving placebo, (p=0.0025). The proportion of subjects with worsening HAE symptoms after receiving treatment was significantly lower in the C1-INH P 20 U/kg treated group (p= 0.001).

Competition: There are two other C1-esterase inhibitors, in the U.S. market. See Rhucin involving C1-esterase inhibitor produced by transgenic rabbits and the entry below for Cinryze/CetorA, another plasma-derived product.

Disease: See the Rhucin entry.