FDA approves first 4-factor PCC for warfarin reversal

FDA has approved prothrombin complex concentrate [human] (Kcentra, CSL Behring), the first nonactivated four-factor PCC, indicated for the urgent reversal of vitamin K antagonist anticoagulation (warfarin) in patients with acute major bleeding.

KCentra is referred to as a four-factor concentrate because it contains factors II, VII, IX, and X -- all of which are low in patients treated with warfarin or other vitamin K antagonists. In three-factor PCCs, there is little to no factor VII.

“The approval of Kcentra, a first-in-class therapy in the United States, means that healthcare professionals now have a new intervention that can efficiently raise the level of clotting factors decreased by warfarin significantly faster and with less volume than plasma,” said Lynne Powell, senior vice president, North America Commercial Operations, CSL Behring. “In an emergency situation, Kcentra is easy to access, as it does not require blood-type matching or thawing, and can be stored for up to 36 months at room temperature.”

Kcentra has clotting factors that are 25 times more concentrated than those in plasma, and it replaces only what’s needed for warfarin reversal.

Three to four million adults in the United States are treated with warfarin each year to prevent blood clots after events such as stroke, heart attack, or atrial fibrillation. Yet for patients taking warfarin, the risk of serious and potentially life-threatening bleeding is always a concern. It’s estimated that U.S. emergency departments see approximately 29,000 cases annually for warfarin-associated bleeding.

In a pivotal randomized, controlled clinical trial comparing Kcentra to plasma, results showed that Kcentra:

· Achieved effective hemostasis in 72.4% of patients versus 65.4% receiving plasma at 24 hours after the start of infusion, thereby achieving the study end point of noninferiority.

· Was superior to plasma in achieving INR reduction to ≤ 1.3 at 30 minutes after the end of the infusion (62.2% and 9.6%, respectively).

· Had a seven times faster infusion time than plasma (mean infusion time was 24 minutes, compared with almost three hours for plasma).

· Restored coagulation factors to a higher level than plasma, with 87% less volume per dose.

The randomized study design also showed, for the first time, that the safety profile of Kcentra was consistent with plasma and that the incidences of adverse reactions (ARs) within 72 hours of the end of infusion were comparable in the Kcentra and plasma groups. The most common ARs observed in patients receiving Kcentra were headache, nausea/vomiting, arthralgia, and hypotension. The most serious ARs were thromboembolic events including stroke, pulmonary embolism, and deep vein thrombosis.

CSL Behring has plans in place to introduce Kcentra to physicians and formulary decision-makers in hospital and institutional settings where they expect the product will be used, Powell said.

Patients being treated with Vitamin K antagonists therapy have underlying disease states that predispose them to thromboembolic events. Both fatal and nonfatal arterial and venous thromboembolic complications have been reported with Kcentra in clinical trials and post-marketing surveillance. Patients receiving Kcentra should be monitored for signs and symptoms of thromboembolic events.