NEW ORLEANS, Dec. 9, 2013 /PRNewswire/ -- Data presented today by CSL Behring at the 55th Annual Meeting of the American Society of Hematology (ASH) showed Kcentra® (Prothrombin Complex Concentrate [Human]) was superior to plasma, the current standard of care in the U.S., in adult patients taking vitamin K antagonist therapy (VKA; e.g., warfarin) who required warfarin reversal prior to an urgent surgery or invasive procedure. Kcentra, the first non-activated 4-factor prothrombin complex concentrate (4F-PCC), was approved by the FDA in April 2013 for the urgent reversal of warfarin therapy in adult patients with acute major bleeding. Kcentra is not indicated for urgent reversal of VKA anticoagulation in patients without acute major bleeding and is not indicated for use in patients on VKA therapy requiring an urgent surgery or invasive procedure as evaluated in this study.
The Phase IIIb study showed that Kcentra was superior to plasma in achieving effective hemostasis (89.7 percent of patients on Kcentra versus 75.3 percent of patients treated with plasma) and early International Normalized Ratio (INR) reduction to less than or equal to 1.3 at 30 minutes after the end of infusion (55.2 percent of patients treated with Kcentra versus 9.9 percent of patients treated with plasma).
"The data demonstrated a strong benefit for Kcentra over plasma for patients on VKAs requiring an urgent surgery or invasive procedure," said Majed Refaai, M.D., Associate Professor, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center. "These data suggest that Kcentra may offer a valuable advance to help physicians and other healthcare professionals rapidly restore coagulation factors and help prevent excessive bleeding in patients on warfarin who require an urgent surgery or intervention, a population highly susceptible to serious and life-threatening bleeds."
The study also found that Kcentra was well-tolerated and that the incidences of adverse events, serious adverse events, thromboembolic events, and deaths were similar between the Kcentra and plasma groups. Additionally, there were no treatment-related fluid overload events in patients receiving Kcentra; fluid overload events occurred significantly more frequently in the plasma group than in the Kcentra group.
Warfarin is used each year by approximately three to four million people in the U.S. to prevent blood clots from forming following a stroke, heart attack, heart valve surgery, deep vein thrombosis/pulmonary embolism, or certain types of irregular heartbeat, such as atrial fibrillation.1,2 Due to the deficiency in blood clotting factors induced by warfarin treatment, patients are at increased risk of bleeding, especially if undergoing an urgent surgery or invasive procedure.
"The results of this study demonstrate the efficacy and safety profiles of Kcentra in helping physicians treat their patients on warfarin therapy when faced with an urgent bleeding threat," said Russell Basser, M.D., Senior Vice President, Global Clinical R&D, CSL Behring. "As a global leader in coagulation therapies, CSL Behring has a long history of developing innovative treatments that address the unmet needs of people with hereditary and acquired bleeding disorders. We are proud to be at the forefront of clinical research that may offer a step forward in treating patients on warfarin therapy who need to undergo an urgent surgery or invasive procedure."
About the Urgent Surgery/Invasive Procedures Clinical Trial
The prospective, randomized, Phase IIIb study included 168 evaluable patients on Vitamin K antagonist therapy who required urgent replacement of their Vitamin K-dependent clotting factors prior to undergoing an urgent surgery or invasive procedure. The doses of Kcentra (25 units/kg, 35 units/kg, or 50 units/kg) based on nominal Factor IX content and plasma (10 mL/kg, 12 mL/kg, or 15 mL/kg) were calculated according to the patient's baseline INR (2-<4, 4-6, >6, respectively) and body weight.
The primary endpoints included hemostatic efficacy for the time period from the start of infusion of Kcentra or plasma until the end of the urgent surgery/invasive procedure and the proportion of patients that achieved INR of less than or equal to 1.3 at 30 minutes after the end of infusion of Kcentra or plasma.
Kcentra contains four vitamin K-dependent factors: Factor II (prothrombin), Factor VII, Factor IX and Factor X, as well as antithrombotic Proteins C and S. In more than 25 countries, CSL Behring markets Kcentra as Beriplex® or Confidex®.
In December 2012, the FDA granted Orphan Drug Designation for Kcentra for the treatment of patients needing urgent reversal of Vitamin K antagonist therapy due to major bleeding and/or surgical procedures. The FDA's Orphan Drug Designation program provides orphan status to unique drugs and biologics defined as those intended for the safe and effective treatment or prevention of rare diseases that affect fewer than 200,000 people in the U.S. Orphan designation qualifies the sponsor of the product for important tax credits, elimination of FDA license application fees and certain marketing incentives.
Important Safety Information
Kcentra®, Prothrombin Complex Concentrate (Human), is indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA -- e.g., warfarin) therapy in adult patients with acute major bleeding. Kcentra is not indicated for urgent reversal of VKA anticoagulation in patients without acute major bleeding. Kcentra is for intravenous use only.
WARNING: ARTERIAL AND VENOUS THROMBOEMBOLIC COMPLICATIONS
Patients being treated with Vitamin K antagonist therapy have underlying disease states that predispose them to thromboembolic events. Potential benefits of reversing VKA should be weighed against the risk of thromboembolic events, especially in patients with history of such events. Resumption of anticoagulation therapy should be carefully considered once the risk of thromboembolic events outweighs the risk of acute bleeding. Both fatal and nonfatal arterial and venous thromboembolic complications have been reported in clinical trials and postmarketing surveillance. Monitor patients receiving Kcentra, and inform them of signs and symptoms of thromboembolic events. Kcentra was not studied in subjects who had a thromboembolic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within the prior 3 months. Kcentra might not be suitable for patients with thromboembolic events in the prior 3 months.
Kcentra is contraindicated in patients with known anaphylactic or severe systemic reactions to Kcentra or any of its components (including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and human albumin). Kcentra is also contraindicated in patients with DIC. Because Kcentra contains heparin, it is contraindicated in patients with heparin-induced thrombocytopenia (HIT).
Hypersensitivity reactions to Kcentra may occur. If patient experiences severe allergic or anaphylactic type reactions, discontinue administration and institute appropriate treatment.
In clinical trials, the most frequent (greater than or equal to 2.8%) adverse reactions observed in subjects receiving Kcentra were headache, nausea/vomiting, arthralgia, and hypotension. The most serious adverse reactions were thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis.
Kcentra is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.
The safety and efficacy of Kcentra in pediatric use have not been studied, and Kcentra should be used in women who are pregnant or nursing only if clearly needed.
For more information about Kcentra, including full prescribing information, please visit www.kcentra.com/prescribing-information.aspx or call toll-free 1-855-4KCENTRA (1-855-452-3687).
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 used around the world to treat coagulation disorders including hemophilia and von Willebrand disease, primary immune deficiencies, hereditary angioedema and inherited respiratory disease, and neurological disorders in certain markets. The company's products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic diseases in the newborn. 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.
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1 Zareh M, Davis A, Henderson S. Reversal of warfarin-induced hemorrhage in the emergency department. West J Emerg Med. 2011;12(4):386-392.
2 Raife TJ, Rose JS, Lentz SR. Bleeding from acquired coagulation defects and antithrombotic therapy. In: Simon TL, Snyder EL, Stowell CP, Strauss RG, Solheim BG, Petrides M, eds. Rossi's Principles of Transfusion Medicine. 4th ed. Hoboken, NJ: Wiley Blackwell; 2009; chapter 24.
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