Kcentra®, from CSL Behring, Receives FDA Approval for Use in Warfarin Reversal in Patients Undergoing Surgery

New Kcentra Label Includes Urgent Reversal of Warfarin in an Emergency Surgery Setting

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Dec 13, 2013, 05:58 ET

KING OF PRUSSIA, Pa., Dec. 13, 2013 /PRNewswire/ -- CSL Behring today announced that Kcentra^® (Prothrombin Complex Concentrate [Human]) has received U.S. Food and Drug Administration (FDA) approval for an expanded indication -- urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients needing an urgent surgery or other invasive procedure. Kcentra, approved by the FDA in April 2013 for the urgent reversal of warfarin therapy in adult patients with acute major bleeding, is the only non-activated 4-factor prothrombin complex concentrate (4F-PCC) indicated in the U.S. for these uses.

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"When patients who are taking warfarin require an urgent surgical or invasive procedure, it is critical to quickly restore their coagulation status," said Joshua N. Goldstein, M.D., Ph.D., Department of Emergency Medicine, Massachusetts General Hospital. "Kcentra is an important new option for such cases; it does not require blood-type matching or thawing, and restores clotting factors more quickly than plasma. We anticipate that emergency physicians, surgeons and other hospital clinicians will welcome the expanded indication."

Kcentra helps restore blood coagulation by replenishing the levels of clotting factors that were depleted by warfarin therapy. 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.

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.

"At CSL Behring, we are committed to improving the lives of people with serious health conditions by continuously working to address unmet medical needs with novel therapies," said Lynne Powell, Senior Vice President, North America Commercial Operations, CSL Behring. "The expanded indication for Kcentra in patients on warfarin therapy needing an urgent surgery or invasive procedure is another example of this commitment."

About the Urgent Surgery/Invasive Procedure Clinical Trial
The prospective, randomized, Phase IIIb study used as the basis for the FDA approval of the expanded indication for Kcentra included 168 evaluable patients on Vitamin K antagonist therapy, e.g., warfarin, who required urgent replacement of their Vitamin K-dependent clotting factors due to the need for an urgent surgery/invasive procedure. Kcentra was superior to plasma in achieving the endpoints of hemostatic efficacy for the time period from the start of infusion of Kcentra or plasma until the end of the urgent surgery or other invasive procedure (89.7 percent of patients treated with Kcentra versus 75.3 percent treated with plasma) and 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 secondary endpoints included plasma levels of major clotting factors (Factors II, VII, IX, X, antithrombotic proteins C and S) and safety and tolerability (including all-cause mortality). A single Kcentra infusion produced a rapid and sustained increase in plasma levels of clotting Factors II, VII, IX, and X within 30 minutes after the end of infusion with 89 percent less volume (90 mL +/-32 mL versus 819 mL +/- 231 mL) than plasma. Additionally, infusion time with Kcentra was nearly seven times faster than with plasma (21 minutes versus 141 minutes for plasma).

Kcentra had a safety profile comparable to plasma. The most common adverse reactions (frequency greater than or equal to 2.8%) observed in patients receiving Kcentra in both the Acute Major Bleeding Study and the Urgent Surgery/Invasive Procedure study were headache, nausea/vomiting, hypotension and anemia. The most serious adverse reactions were thromboembolic events including stroke, pulmonary embolism and deep vein thrombosis.

About Kcentra^®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 a blood coagulation factor replacement product 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 or the need for urgent surgery or other invasive procedure. 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 disseminated intravascular coagulation. 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, hypotension, and anemia. 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, please visit www.kcentra.com or call toll-free 1-855-4KCENTRA. For full prescribing information, please visit www.kcentra.com/prescribing-information.aspx.

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.

Media Contacts:

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

Etanjalie Ayala
Weber Shandwick
1-212-445-8225
[email protected]

[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.

SOURCE CSL Behring