(188) Twenty Years of 4-Factor Prothrombin Complex Concentrate: Review and Advances of Octaplex/Balfaxar

Introduction: Octaplex®/Balfaxar® (Octapharma AG, Switzerland) is an intravenously administered four-factor freeze-dried human prothrombin complex concentrate (4F-PCC) available since 2003 and approved in 87 countries, including the USA. 4F-PCC is used for the treatment and perioperative prophylaxis of bleeding in congenital or acquired vitamin K-dependent coagulation factor deficiency, and is being investigated for direct oral anticoagulant (DOAC)-associated bleeds and coagulation factor deficiency during cardiac surgery. We review the efficacy and safety of Octapharma’s 4F-PCC and recent advances in clinical research.

Methods: We reviewed all studies of Octaplex®/Balfaxar®, including literature searches of “octaplex” using PubMed, Google Scholar and Clinicaltrials.gov to capture studies reporting clinical safety and efficacy.

Results: The Octapharma clinical trial program for Octaplex®/Balfaxar® included 7 studies: 5 completed (n=444) and 2 ongoing in DOAC reversal and cardiac surgery. Five published studies of urgent reversal of vitamin K antagonists (VKA) for bleeding or perioperative prophylaxis are reported. In a head-to-head Phase III randomized double-blind study (n=208), Octaplex®/Balfaxar® was non-inferior to control 4F-PCC (Kcentra®, CSL Behring) in achieving hemostatic efficacy with similar INR correction and safety profiles. Additionally, other studies of 4F-PCC in patients treated for urgent reversal of VKA, showed effective hemostasis and rapid correction of INR. Proportions of TEEs were low and not significantly different between groups. In a study of 20 patients, excellent hemostatic efficacy was achieved for 85% after a single infusion and in another study (n=56), the timely correction of INR to target levels was achieved for 91% of patients. A randomized, phase II investigator-led study (FARES) evaluated Octaplex® and FFP in patients undergoing cardiac surgery with cardiopulmonary bypass. The Octaplex® group (n=54) required significantly reduced additional hemostatic therapy compared with the FFP group (n=47) and used fewer allogeneic blood products.

Conclusions: Multiple clinical studies have shown that Octaplex®/Balfaxar® is an effective hemostatic agent for various indications including VKA reversal, with a favorable safety profile. Ongoing studies are expanding the role of 4F-PCC.