The US Food and Drug Administration (FDA) has approved CSL Behring's Kcentra (Prothrombin Complex Concentrate [Human]) 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 US for these uses.
“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, 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 US 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.”
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 haemostatic 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 per cent of patients treated with Kcentra versus 75.3 per cent treated with plasma) and INR reduction (to =1.3) at 30 minutes after the end of infusion (55.2 per cent of patients treated with Kcentra versus 9.9 per cent 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 per cent 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 =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 anaemia. The most serious adverse reactions were thromboembolic events including stroke, pulmonary embolism and deep vein thrombosis.
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 US Orphan designation qualifies the sponsor of the product for important tax credits, elimination of FDA license application fees and certain marketing incentives.
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.