CSL Behring today announced that the Centers for Medicare and Medicaid Services (CMS) has approved a new technology add-on payment (NTAP) for Kcentra™ (Prothrombin Complex Concentrate [Human]) for use in the inpatient hospital setting for the urgent reversal of warfarin therapy in adult patients with acute major bleeding. Kcentra, the first non-activated 4-factor prothrombin complex concentrate (4F-PCC), was approved by the U.S. Food and Drug Administration (FDA) in April 2013 for this use.
"The CMS NTAP approval recognizes that Kcentra is a significant clinical advancement for reversing the effects of warfarin in patients who experience acute major bleeding,” said Lynne Powell, Senior Vice President, North America Commercial Operations, CSL Behring. “This approval will help facilitate adoption of Kcentra among healthcare professionals who treat Medicare patients on warfarin therapy by providing broader access to Kcentra."
About the New Technology Add-On Payment Policy
The CMS NTAP policy was implemented in 2001 to support timely access to innovative therapies for Medicare beneficiaries in the inpatient hospital setting that are not adequately paid for under the Medicare Severity Diagnosis-Related Groups (MS-DRGs). To be eligible for an NTAP, the new product must provide a substantial clinical improvement over existing therapies. Beginning October 1, 2013, CMS will reimburse hospitals an additional amount, up to $1,587.50, for cases involving Kcentra that exceed the MS-DRG payment amount. This add-on payment for Kcentra will continue for at least two years.
For more information on the CMS NTAP approval for Kcentra, please visit https://s3.amazonaws.com/public-inspection.federalregister.gov/2013-18956.pdf.
Prevalence of Warfarin Therapy
Each year, approximately three to four million people in the U.S. are treated with the oral anticoagulant 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. However, because of the deficiency in blood clotting factors induced by warfarin treatment, patients may experience severe bleeding. It is estimated that emergency departments in the U.S. see approximately 29,000 cases annually for warfarin-associated bleeding.3
About the Kcentra Pivotal Clinical Trial
The randomized, controlled Phase IIIb study used as the basis for the FDA approval of Kcentra was the first prospective analysis to compare a 4-factor PCC and vitamin K with plasma and vitamin K for urgent warfarin reversal in patients with acute major bleeding. Kcentra achieved the endpoints of hemostatic efficacy with respect to the adequacy of stopping a major bleed assessed over 24 hours from the start of infusion (72.4 percent of patients receiving Kcentra versus 65.4 percent receiving plasma) and INR reduction (≤1.3) at 30 minutes post treatment (62.2 percent of patients receiving Kcentra versus 9.6 percent receiving plasma).
The secondary endpoints included plasma levels of major clotting factors (Factors II, VII, IX, X, proteins C and S); time to INR correction; 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 post-treatment (p values<0.0001) with 87 percent less volume (105 mL +/-37 mL versus 865 mL +/- 269 mL) than plasma. Additionally, infusion time with Kcentra was seven times faster than with plasma (24 minutes versus nearly 3 hours for plasma).
The most common adverse reactions (frequency ≥2.8%) 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.
About Kcentra™
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
Warning: 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 (DIC), cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within the prior three months. Kcentra might not be suitable in patients with thromboembolic events in the prior three months.
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.
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 (≥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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Media Contact:
Greg Healy
Senior Manager, Public Relations & Communications
CSL Behring
1-610-878-4841
greg.healy@cslbehring.com
- 1. Zareh M, Davis A, Henderson S. Reversal of Warfarin-Induced Hemorrhage in the Emergency Department. West J Emerg Med. 2011 November; 12(4): 386–392.
- 2. Rossi’s Principles of Transfusion Medicine, 4th edn. Chapter 24: Bleeding from Acquired Coagulation Defects and antithrombotic therapy – Thomas J. Raife, Jeffrey S. Rose, & Steven R. Lentz. ISBN: 978-1-4051-7588-3
- 3. Wysowski D, Nourjah P, Swartz L. Bleeding complications with warfarin use: A prevalent adverse effect resulting in regulatory action. Arch Intern Med. 2007; 167 (13) : 1414-1419