FDA approves Kcentra for urgent warfarin reversal in patients with acute major bleeding

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On 30 April, the FDA approved CSL Behring’s Kcentra (Prothrombin complex concentrate [human]), the first non-activated 4-factor prothrombin complex concentrate for the urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (eg. warfarin) therapy in adult patients with acute major bleeding.

The pivotal clinical trial, supporting the approval, showed that Kcentra met all efficacy and safety endpoints, including the endpoints of haemostatic efficacy and International Normalised Ratio (INR) reduction compared with plasma, the most widely used agent for warfarin reversal in the United States.

“Kcentra has been shown to restore the decreased vitamin K-dependent clotting factors significantly faster than plasma in patients on warfarin,” said Ravi Sarode, professor of Pathology and Director of Transfusion Medicine and Hemostasis Reference Laboratory at the University of Texas Southwestern Medical Center, and coordinating investigator for the Kcentra trial.


“FDA approval of Kcentra is an important advancement in warfarin reversal, as it provides medical professionals with a new tool that can efficiently stop major bleeding in patients for whom plasma may not be optimal,” said Lynne Powell, senior vice president, North America Commercial Operations, CSL Behring. “Kcentra is CSL Behring’s fifth FDA product approval since 2009. This record of success further underscores our commitment to innovation and bringing therapies to market that effectively treat and manage serious medical conditions.”


About the pivotal clinical trial of Kcentra


The randomised, controlled phase IIIb study of Kcentra enrolled 212 evaluable patients and was the first prospective analysis to compare a 4-factor prothrombin complex concentrate and vitamin K with plasma and vitamin K for urgent warfarin reversal in patients with acute major bleeding. Kcentraachieved the endpoints of haemostatic efficacy with respect to the adequacy of stopping a major bleed assessed at 24 hours from the start of infusion (72.4% of patients receiving Kcentravs. 65.4% receiving plasma) and INR reduction (≤1.3) at 30 minutes post treatment (62.2% of patients receivingKcentra vs. 9.6% 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 singleKcentrainfusion produced a rapid and sustained increase in plasma levelsof clotting factors II, VII, IX, and X within 30 minutes post-treatment (p values<0.0001) with 87% 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 three hours for plasma).


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.