FDA Approves Complex for Urgent Reversal of Excess Bleeding in Surgery

The FDA has approved prothrombin complex concentrate, human-Ians (Balfaxar; Octapharma USA) for the urgent reversal of acquired coagulation factor deficiency in adults who need an urgent surgery or invasive procedure and are currently taking a vitamin K antagonist (warfarin), according to a press release.¹

The approval was based on the results of the LEX-209 (NCT02740335) study, a phase 3, randomized, double-blind, multicenter trial that compared the safety and efficacy of prothrombin complex concentrate, human-lans against 4F-PCC (Kcentra; CSL Behring) in 208 patients. The primary endpoint of LEX-209 was hemostatic efficacy—or effective blood stoppage, primary investigator Ravi Sarode, MD, noted in the press release.

“[Prothrombin complex concentrate, human-lans] was non-inferior to the comparator in patients on a vitamin K antagonist undergoing urgent surgery with significant bleeding risk,” Sarode said.

According to the trial results, at least 94.6% of patients who were given the novel complex achieved hemostasis compared to 93.5% of patients who received the control (4F-PCC). Further, prothrombin complex concentrate, human-lans demonstrated a similar safety profile that is consistent with previous studies, according to Sarode.

Prothrombin complex concentrate, human-lans even performed so well at the prespecified interim analysis that investigators stopped the study, Sarode said in the press release.

“The primary objective was met at the prespecified interim analysis and the study was stopped due to statistically significant efficacy results indicating that [prothrombin complex concentrate, human-lans] was non-inferior to [4F-PCC],” Sarode said in the press release.

Warfarin is a common vitamin K antagonist that is prescribed to more than 2.4 million people in the United States. Warfarin is used to prevent blood clots and is usually administered to patients who have had a heart attack, heart valve surgery, stroke, deep vein thrombosis/pulmonary embolism, or have irregular heartbeat.

However, warfarin can lead to deficiency of vitamin K-dependent coagulation factors (Factor II (prothrombin), Factor VII, Factor IX and Factor X, and antithrombotic Proteins C and S), which can cause excess bleeding. This can be especially dangerous for patients who have an immediate need for surgery or invasive procedure. Prothrombin complex concentrate, human-lans works by replacing these deficient blood coagulation factors.^1,2

Prothrombin complex concentrate, human-lans takes the form of a lyophilized powder that is combined with sterile water and injected via reconstitution transfer device (nextaro; sfm medical devices); this device, which was used in the preference study, contains vial housing that allows for vial precentering at mounting and 2 integrated filters that offer protection against contaminants.¹

“The FDA approval of Balfaxar establishes a new therapy for medical providers when their patients need a 4F-PCC product,” said Flemming Nielsen, president of Octapharma USA, in the press release.

References

1. Octapharma's prothrombin complex concentrate, Balfaxar®, receives FDA approval for warfarin reversal in urgent surgery & invasive procedures. Yankee Public Relations. July 26, 2023. Accessed on July 26, 2023. https://www.eurekalert.org/news-releases/996739
2. Vitamin K Deficiency. Cornell University. Accessed July 26, 2023. https://www.vet.cornell.edu/animal-health-diagnostic-center/testing/protocols/vitamin-k-deficiency#:~:text=Overview,of%20normal%20fibrin%20clot%20formation.