CSL Behring today announced that The Lancet has published results from a Phase III clinical study showing Kcentra® (Prothrombin Complex Concentrate [Human]) to be superior to plasma for the 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 invasive procedure. Kcentra is the first and only non-activated 4-factor prothrombin complex concentrate (4F-PCC) approved by the U.S. Food and Drug Administration (FDA) for this use and for the urgent reversal of warfarin therapy in adult patients with acute major bleeding.
Each year, approximately three to four million people in the U.S. use warfarin 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 a 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 the Phase III study published in The Lancet show that Kcentra is more effective than plasma for INR [international normalized ratio] reduction and periprocedural hemostasis in adults who are taking warfarin and require an urgent procedure," said lead study author Joshua N. Goldstein, M.D., Ph.D., attending physician in the Department of Emergency Medicine at Massachusetts General Hospital.
Results of the multicenter, open-label, phase IIIb randomized trial showed that in 168 evaluable patients, 90 percent of patients treated with Kcentra achieved effective hemostasis, compared to 75 percent of patients treated with plasma. Additionally, INR reduction to ≤1.3 at 30 minutes after the end of infusion was achieved in 55 percent of patients treated with Kcentra versus 10 percent of patients treated with plasma. Incidences of adverse events, serious adverse events, thromboembolic events, and deaths were similar between the Kcentra and plasma groups. In post-hoc analysis, the median time from start of infusion to start of urgent surgical procedure was shorter in the Kcentra group (3.6 hours [IQR 1.9–10.8]) than in the plasma group (8.5 hours [IQR 2.8–18.7]); (p=0.0098).
"CSL Behring has long been at the forefront of developing innovative protein therapies to help healthcare professionals treat patients with serious medical conditions," said Bill Campbell, Senior Vice President, North America Commercial Operations, CSL Behring. "Kcentra further underscores our commitment by providing physicians with a treatment option to prevent and manage the risks of excessive bleeding in patients on warfarin who need to undergo an urgent surgery or invasive procedure."
Kcentra was first approved for use in the U.S. in April 2013 and received a new technology add-on payment (NTAP) designation from the Centers for Medicare and Medicaid Services through September 2015. To be eligible for an NTAP, the product must be new and inadequately paid for under existing MS-DRGs, and must provide a significant clinical improvement over existing therapies.
In more than 25 countries, CSL Behring markets Kcentra as Beriplex® or Confidex®. In December 2012, the FDA granted Orphan Drug Designation to 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 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 three months. Kcentra might not be suitable for patients with thromboembolic events in the prior three 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 (≥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 disease of the newborn.
CSL Behring operates one of the world’s largest plasma collection networks, CSL Plasma. CSL Behring is a global biopharmaceutical company and a member of the CSL Group of companies. The parent company, CSL Limited (ASX:CSL), is headquartered in Melbourne, Australia. For more information, visit www.cslbehring.com.