Balfaxar (prothrombin complex concentrate, human-lans) / Octapharma - LARVOL DELTA

Prothrombin complex concentrate in managing direct oral anticoagulant (DOAC)-associated bleeding and real-world use in vitamin k antagonist (VKA)-associated bleeding: The ongoing lex-210 and lex-212 studies (ASH 2025) - P, P3 | "The LEX-212 study aims to assess the safety of Balfaxar vs. a comparator 4F-PCC(Kcentra/Beriplex, CSL Behring) for the urgent reversal of VKA-induced anticoagulation in real-worldsurgical settings, complementing evidence from clinical trials.Study Design and LEX-210 (NCT04867837) is a Phase 3, multicenter, prospective, double-blinded, group‑sequential, parallel-group, adaptive design study with a preplanned interim analysis for potential sample size modification.Approximately 260 patients aged ≥18 years with acute major bleeding while on FXaI therapy will berandomized 1:1 to receive low-dose (15 IU/kg) or high-dose (50 IU/kg) 4F-PCC, with the aim to include atleast 91 evaluable patients in each group in the full analysis set (FAS). LEX-212 isconducted in the US; the study started in Q1 2025 and has one site initiated and 14 patients enrolled sofar, with the study end expected in Q2 2032. These studies will expand the understanding of 4F-PCCs inthe context of..."

Clinical • Real-world • Real-world evidence • Cardiovascular

Safety of prothrombin complex concentrate for emergency surgery according to the oral factor xa inhibitor level (ASH 2025) - "The PCC used was almost exclusively Octaplex (Octapharma)...The study was approved by Hamilton IntegratedResearch Ethics Board. PCC at a median dose of 2000 units (interquartile range, 2000-2000) was administered to 224patients on apixaban (142; 63%), rivaroxaban (71; 32%) or edoxaban (11; 5%) for emergency surgery orinvasive procedures... The risk of thromboembolic events after 4F-PCC for management of hemostasis in patientson XaI and emergency surgery/invasive procedures appears to be similar among patients withpreoperative drug levels that are high, low or not measured. These findings support the safe use of PCCin settings where rapid anti‑Xa testing is unavailable."

Clinical • Surgery • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Myocardial Infarction • Respiratory Diseases • Venous Thromboembolism

Randomized, Active-Control Phase 3 Study of Four-Factor Prothrombin Complex Concentrate Versus Frozen Plasma in Bleeding Adult Cardiac Surgery Patients (ASH 2023) - P3 | "The LEX-211 (FARES-II) study will determine if four-factor PCC (4F-PCC, Octaplex, Octapharma) is clinically non-inferior to FP regarding hemostatic effectiveness in cardiac surgery patients requiring coagulation factor replacement...Completion is expected in Q4 2024. The results of this study will inform clinical practice for bleeding cardiac surgery patients requiring coagulation factor replacement, potentially reducing allogeneic blood product usage and improving patient outcomes."

Clinical • P3 data • Surgery • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders

Updated Protocol for the Phase 3, Randomized, Double-Blinded Lex-210 Study of Four-Factor Prothrombin Complex Concentrate in Patients with Acute Major Bleeding on Factor Xa Inhibitor Therapy (ASH 2023) - P3 | "This study aims to evaluate superior hemostatic efficacy of high-dose vs low-dose four-factor (4F) PCC (Octaplex®; Octapharma) in adults with FXaI-related major bleeding...So far, 26 sites in the US, Italy, Germany, and Spain have been initiated, with 5 patients enrolled. Study completion is anticipated in Q3 2024."

Clinical • P3 data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Immunology

Rapido: Results from a UK-Wide Audit of 2477 Patients Who Received a Reversal Agent for a Direct Oral Anticoagulant (ASH 2024) - "Although a specific reversal agent for dabigatran, idarucizumab, was approved for use in the UK in 2016, the predominant option for patients taking apixaban, edoxaban, and rivaroxaban has until recently been off-licence prothrombin complex concentrate (PCC). Importantly, the data highlight delays in identification and treatment of bleeds. Further, detailed analysis of this rich dataset is on-going, and a propensity score-matched analysis of patients with GI hemorrhage will be performed to compare outcomes in patients treated with andexanet alfa, Beriplex and Octaplex."

Clinical • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Venous Thromboembolism

Redefining Mallory-Weiss Tears: A Case of Life-Threatening Anemia and Hypoxic Respiratory Failure (ACG 2025) - "Apixaban was reversed with balfaxar, and desmopressin was given for aspirin use...She was started on a pantoprazole for presumed upper GI bleeding...Endoscopic evaluation enabled timely diagnosis and intervention. This case demonstrates how identifying non-pulmonary contributors to hypoxia is essential, and how prompt hemostasis and hemoglobin restoration can reverse respiratory compromise."

Clinical • Acute Respiratory Distress Syndrome • Anemia • Cardiovascular • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Hematological Disorders • Hypotension • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

Hemostatic Efficacy of Prothrombin Complex Concentrate for Managing Coagulopathic Bleeding in Surgical Patients: Results from the LEX-209 and LEX-211 (FARES-II) Phase 3 Trials (AABB 2025) - P3 | "The LEX-209 and LEX-211 Phase 3 randomized controlled trials assessed the efficacy and safety of investigational PCC (Octaplex/Balfaxar) in patients undergoing urgent VKA reversal or cardiac surgery with elevated INR. Study Design/ LEX-209 (NCT02740335) was a double-blind, non-inferiority trial comparing investigational vs. control PCC (Beriplex/Kcentra) in adults (≥18 years) with INR ≥2.0 receiving VKAs prior to urgent surgery... PCC administration demonstrated rapid INR correction in VKA-associated coagulopathy vs. control PCC and significantly greater INR reduction following CPB-associated coagulopathy vs. FP."

Clinical • P3 data • Acute Kidney Injury • Cardiovascular • Hematological Disorders • Nephrology • Renal Disease

Prothrombin Complex Concentrate Reduces Transfusion Need vs Plasma in Cardiac Surgery Patients: The FARES-II Study (ASA 2025) - P3 | " The FARES-II (LEX-211; NCT05523297) phase 3, prospective, multicenter, randomized, non-inferiority, controlled trial compared PCC with FP in patients ≥18 years undergoing cardiac surgery with cardiopulmonary bypass (CPB) who developed bleeding related to coagulation factor deficiency, at 12 sites in Canada and the U.S. Patients were randomized in the operating room (OR) to PCC (Octaplex®/Balfaxar®, Octapharma; 1500 IU if ≤60 kg, 2000 IU if >60 kg) or FP (3 U if ≤60 kg, 4 U if >60 kg)... Transfusion requirements were significantly lower in cardiac surgery patients with excessive bleeding related to coagulation factor deficiency treated with PCC compared with FP."

Clinical • Surgery • Acute Kidney Injury • Cardiovascular • Nephrology • Renal Disease

Twenty Years of the Four-Factor Prothrombin Complex Concentrate Octaplex/Balfaxar (ASA 2025) - "This 4F-PCC is approved for acquired deficiency of vitamin K-dependent clotting factors, such as those induced by vitamin K antagonists (VKAs, e.g., warfarin), and for congenital deficiency of factors II and X. It has now been approved for use in 89 countries worldwide, including the United States (since 2023), and has been administered to approximately 1.5 million patients worldwide. Octaplex/Balfaxar has now been available for use in clinical settings for over 20 years and is approved for a range of uses. Ongoing prospective studies will further clarify the efficacy and safety of this 4F-PCC beyond its approved indications."

Cardiovascular • Hematological Disorders • Pediatrics • Thrombosis

Prothrombin Complex Concentrate Reduces Severe Bleeding vs Plasma in Cardiac Surgery Patients: The FARES-II Study (ASA 2025) - P3 | "Patients aged ≥18 years undergoing cardiac surgery with cardiopulmonary bypass (CPB) and who developed bleeding related to coagulation factor deficiency were randomized to PCC (Octaplex®/Balfaxar®, Octapharma; 1500 IU if ≤60 kg, 2000 IU if >60 kg) or FP (3 U if ≤60 kg, 4 U if >60 kg) in the operating room... PCC significantly reduced the incidence of severe to massive bleeding compared with FP in bleeding cardiac surgery patients requiring coagulation factor replacement."

Clinical • Surgery • Acute Kidney Injury • Cardiovascular • Nephrology • Renal Disease

Biochemical analysis of anticoagulant compounds in four-factor prothrombin complex concentrates (ISTH 2025) - "Aims To characterize pro- and anticoagulant content of three 4F-PCCs, Prothromplex (PKT; Takeda), Kcentra (KCT; CSL Behring), and Octaplex (OTX; Octapharma), and explore the effect of 4F-PCC heparin content on thrombin generation in vitro. Following heparin removal, PKT resulted in the highest increase in peak thrombin in normal plasma; in anticoagulated plasma, similar thrombin levels were observed for all 4F-PCCs. Table or Figure Upload"

Superiority of four-factor prothrombin complex concentrate vs. frozen plasma for bleeding management in adult cardiac surgery patients with coagulopathy: results from a phase 3, randomised, active-control study (Euroanaesthesia 2025) - P3 | "This trial compared the efficacy and safety of PCC (Octaplex/BALFAXAR, Octapharma) with FP in cardiac surgery.Materials and LEX-211 (FARES-II; NCT05523297) was conducted at 12 sites in Canada and the U.S. Patients (pts) aged ≥18 years undergoing cardiac surgery with CPB with coagulopathic bleeding, international normalised ratio (INR) ≥1.5, and requiring coagulation factor replacement, were randomised 1:1 to receive PCC (1500 IU if ≤60 kg; 2000 IU if >60 kg) or FP (3 U if ≤60 kg; 4 U if >60 kg)...Severe to massive bleeding within 24 h after the start of surgery was lower in PCC pts vs. FP pts (17.4% vs. 37.7%; p<0.0001). Thirty-day treatment-emergent thromboembolic events and mortality occurred in 8.5% and 3.3% of PCC pts and 7.2% and 3.9% of FP pts, respectively.Conclusion(s): Results from the phase 3, randomised, active-control LEX-211 study support the use of PCC over FP for bleeding management in cardiac surgery."

Clinical • Head-to-Head • P3 data • Surgery • Cardiovascular • Hematological Disorders

LEX-210: Study of OCTAPLEX in Patients With Acute Major Bleeding on DOAC Therapy With Factor Xa Inhibitor (clinicaltrials.gov) - P3 | N=260 | Recruiting | Sponsor: Octapharma | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date

Twenty years of the four-factor prothrombin complex concentrate Octaplex/Balfaxar: A narrative review. (PubMed, Transfus Apher Sci) - "4F-PCC is approved for acquired deficiency of vitamin K-dependent clotting factors, such as those induced by vitamin K antagonists (VKAs, e.g., warfarin), and for congenital deficiency of factors II and X. Five published trials in 444 adult patients demonstrated the efficacy of 4F-PCC in VKA reversal, reducing the international normalized ratio (INR) with only two potentially treatment-related thrombotic events reported. Recent guidelines support 4 F-PCC use for direct oral anticoagulant-associated bleeding, cardiac surgery and trauma/emergencies. Ongoing studies will further clarify the efficacy and safety of 4 F-PCC beyond its approved indications."

Journal • Review • Cardiovascular • Critical care • Hematological Disorders • Thrombosis

Post Marketing Observational Study on Safety of BALFAXAR vs. KCENTRA for Reversal of Vitamin K Antagonist Induced Anticoagulation in Adults Undergoing Urgent Surgery or Invasive Procedure (clinicaltrials.gov) - P=N/A | N=3574 | Recruiting | Sponsor: Octapharma | Not yet recruiting ➔ Recruiting | Initiation date: Jun 2024 ➔ Jan 2025

Enrollment open • Trial initiation date

EFFICACY AND SAFETY OF HIGH-DOSE FOUR-FACTOR PROTHROMBIN COMPLEX CONCENTRATE: LEX-209 SUBANALYSIS (SCCM 2025) - P3 | "Introduction: The LEX-209 Phase 3 randomized controlled trial of investigational four-factor prothrombin complex concentrate (4F-PCC; Octaplex®/Balfaxar®, Octapharma) demonstrated hemostatic non-inferiority to the FDA-approved control 4F-PCC (Beriplex®/Kcentra®, CSL Behring) in rapid vitamin K antagonist (VKA) reversal before urgent surgery (p< 0.001). Investigational 4F-PCC, administered at the maximum permitted dose, appeared to be safe and effective for rapid VKA reversal in urgent surgery patients with significant bleeding risk. These findings further support the use of high-dose 4F-PCC for surgical patients needing rapid VKA reversal."

Clinical • Hematological Disorders

Evaluation of Balfaxar for anticoagulation reversal in a community hospital (ASHP 2024) - No abstract available

Clinical

Impact of pharmacistled bedside preparation of 4factor PCC Balfaxar in the emergency department (ASHP 2024) - No abstract available

Protocol for a phase 3, randomised, active-control study of four-factor prothrombin complex concentrate versus frozen plasma in bleeding adult cardiac surgery patients requiring coagulation factor replacement: the LEX-211 (FARES-II) trial. (PubMed, BMJ Open) - P3 | "The primary objective is to determine whether 4F-PCC (Octaplex/Balfaxar, Octapharma) is clinically non-inferior to FP for haemostatic effectiveness...The results will advance our understanding of coagulation management in bleeding surgical patients, potentially reducing the need for allogeneic blood products and improving outcomes in surgical patients. NCT05523297."

Clinical protocol • Journal • P3 data • Surgery • Cardiovascular • Hematological Disorders

FARES-2: Active-control Randomised Trial Comparing 4-factor Prothrombin Complex Concentrate With Frozen Plasma in Cardiac Surgery (clinicaltrials.gov) - P3 | N=419 | Completed | Sponsor: Octapharma | Recruiting ➔ Completed

Surgery • Trial completion • Cardiovascular

PROTHROMBIN COMPLEX CONCENTRATE USAGE IN UNIVERSITY COLLEGE LONDON HOSPITALS, A RETROSPECTIVE AUDIT (EHA 2024) - "Aims: -Assessment of the use of PCC Prothrombin Complex Concentrate (Octaplex®) at UCLH, including theindications for use and profile of patients requiring it. Our findings demonstrate 100% compliance with the NICE guidance. We did not identify any inappropriate use or waste of PCC. We demonstrate high rates of thrombosis following use of PCC and therefore clinicians need to consider a riskbenefit approach in patient at risk of thrombosis."

Retrospective data • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Hypertension • Oncology • Pulmonary Embolism • Renal Disease • Respiratory Diseases

Prothrombin complex concentrate for prophylaxis in a patient with Factor II deficiency, a case report (ISTH 2024) - "We initiated prothrombin complex concentrate (Octaplex®, Octapharma AG) at a dose of 20 IU/kg every 3 days, aiming at a minimum FII of 10%4. The patient showed an improvement of the PBQ score to 5 points within the first month of treatment and currently has no increased bleeding. Conclusion(s) : This case underscores the complexities associated with FII deficiency and emphasizes the utility of PCC-based prophylaxis, which should be a tailored intervention based on symptom severity and burden, aiming not only for symtomatic control, but specialy for restoring quality of life."

Case report • Clinical • Hematological Disorders • Osteoarthritis • Pediatrics

A PHASE 3, RANDOMIZED, ACTIVE-CONTROL STUDY OF FOUR-FACTOR PROTHROMBIN COMPLEX CONCENTRATE VERSUS FROZEN PLASMA IN BLEEDING ADULT CARDIAC SURGERY PATIENTS (THSNA 2024) - P3 | "Objective: The LEX-211 (FARES-II) study will determine if four-factor PCC (4F-PCC, Octaplex, Octapharma) is clinically non-inferior to FP regarding hemostatic efficacy in patients undergoing cardiac surgery with coagulation factor deficiency... The study findings have the potential to improve clinical approaches to bleeding management in cardiac surgery patients. Optimizing the management of bleeding related to coagulation factor deficiency may reduce the need for allogeneic blood products and has the potential to improve outcomes in surgical patients."

Clinical • P3 data • Surgery • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Transplantation

An investigational four-factor prothrombin complex concentrate for vitamin k antagonist reversal: hemostatic efficacy and safety demonstrated with and without concurrent vitamin k therapy (ISICEM 2024) - "LEX -209 was a Phase 3 non -inferiority randomized control trial of an investigational 4F -PCC (Octaplex®, Octapharma), which demonstrated hemostatic non -inferiority to the FDA-approved control 4F -PCC (Kcentra®, CSL Behring) in rapid vitamin K antagonist (VKA) reversal before urgent surgery (P<0.001). Investigational 4F -PCC was hemostatically non -inferior to control 4F -PCC for rapid VKA reversal in patients requiring urgent surgery with significant bleeding risk, regardless of concomitant vitamin K therapy. These findings support consideration of investigational 4F -PCC as a therapeutic option for surgical patients requiring rapid VKA reversal."

Clinical • Hematological Disorders

Balfaxar: Another four-factor PCC for warfarin reversal. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal