Analysis Finds Safety of 4-Factor Prothrombin Complex Concentrate Is Consistent With the Current Standard Treatment for Vitamin K Antagonist Reversal

CHICAGO, May 4, 2012 /PRNewswire/ -- Data presented by CSL Behring today at the 2012 Thrombosis and Hemostasis Summit of North America (THSNA) showed that the safety profile of human 4-factor prothrombin complex concentrate (PCC) is consistent with the current standard of treatment in patients receiving vitamin K antagonist therapy (i.e., warfarin) for acute bleeding or prior to emergency surgery. The results are from the first large-scale controlled clinical trials comparing a 4-factor PCC with fresh frozen plasma, the current standard of treatment in the United States.

The safety analysis involved pooled data from three open-label, multinational studies involving a total of 369 patients across multiple centers. The primary and secondary analyses showed that the proportion of subjects with one or more treatment-emergent adverse event (TEAE) was similar in the PCC and plasma groups. The secondary analysis also revealed that the incidence of fluid overload events – when excessive fluid is transfused or too rapidly transfused, which can lead to cardiac events – was higher in the plasma group than in the PCC group (13.2 percent and 4.0 percent, respectively). The most common TEAEs in PCC-treated patients were gastrointestinal disorders; respiratory, thoracic (chest cavity) and mediastinal (central chest cavity) disorders, and nervous system disorders. Thromboembolic events considered possibly related to treatment were similar between the PCC group and plasma group.

"Major bleeding events in patients receiving vitamin K antagonists such as warfarin can be life-threatening, which makes timely anticoagulation reversal imperative," said Joshua N. Goldstein, M.D., Ph.D., Department of Emergency Medicine, Massachusetts General Hospital. "This analysis showed that the safety profile of 4-factor PCC is comparable to plasma, the most commonly used intervention for warfarin reversal in the U.S. In fact, 4-factor PCC may show a lower risk of volume overload."

The study also found that the incidences of severe TEAEs, serious adverse events, and deaths were generally similar between the PCC and plasma groups in both the primary and secondary analysis groups. The proportion of subjects in the primary safety analysis with at least possibly treatment-related TEAEs, as judged by the investigator, was higher in the plasma group (19.2 percent) than in the PCC group (8.2 percent).

"We are very encouraged by the results of this analysis showing comparable safety between 4-factor PCC and plasma for urgent warfarin reversal," said Russell Basser, M.D., Senior Vice President, Global Clinical R&D, at CSL Behring. "CSL Behring has been at the forefront of providing safe and effective therapies for coagulation and we look forward to bringing treatments that address real unmet needs, such as our investigational 4-factor PCC, to patients and physicians in the United States."

About Prothrombin Complex Concentrate (PCC) (Human)

Prothrombin complex concentrates (PCC) are derived from human plasma. CSL Behring's investigational PCC contains four important pro-coagulant factors in significant quantities: Factor II (prothrombin), Factor VII, Factor IX and Factor X, as well as anticoagulant Proteins C and S.

Guidelines from the American College of Chest Physicians recommend 4-factor PCC, rather than plasma, for rapid reversal of anticoagulation in patients with vitamin K antagonist associated major bleeding. The guidelines also recommend the use of vitamin K (5 to10 mg) administered by slow intravenous (IV) infusion rather than reversal with coagulation factors alone.

About the Analysis

This descriptive analysis comprised adverse event data from three open-label, multinational studies involving a total of 369 patients across multiple centers, the majority of which were in the United States. The primary analysis is integrated data from two randomized, controlled studies, while the secondary analysis also includes data from a third uncontrolled study. Patients in the studies required urgent reversal of vitamin K antagonist due to acute major bleeding or need for an urgent procedure for which they were at risk of bleeding. Dosages of PCC and plasma were administered according to body weight and baseline International Normalized Ratio (INR) correction.  Most patients were age 65 or older and most commonly were prescribed warfarin therapy for treatment of atrial fibrillation or deep vein thrombosis.

About CSL Behring

CSL Behring is a leader in the plasma protein therapeutics industry. Committed to saving lives and improving the quality of life for people with rare and serious diseases, the company manufactures and markets a range of plasma-derived and recombinant therapies worldwide. CSL Behring therapies are indicated for the treatment of coagulation disorders including hemophilia and von Willebrand disease, primary immune deficiencies, hereditary angioedema and inherited respiratory disease. The company's products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic diseases in newborns. CSL Behring operates one of the world's largest plasma collection networks, CSL Plasma. CSL Behring is a subsidiary of CSL Limited  (ASX: CSL), a biopharmaceutical company headquartered in Melbourne, Australia. For more information, visit www.cslbehring.com.

Media Contacts:

Greg Healy
Senior Manager, Public Relations & Communications
CSL Behring
1-610-878-4841
[email protected]

Etanjalie Ayala
Weber Shandwick
212-445-8225
[email protected]

SOURCE CSL Behring