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

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

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 • Gastrointestinal Disorder • Hematological Disorders • Venous Thromboembolism

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

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 | N=200 ➔ 260 | Trial completion date: Feb 2024 ➔ Dec 2024 | Trial primary completion date: Jan 2024 ➔ Dec 2024

Enrollment change • Trial completion date • Trial primary completion date

Twenty Years of 4-Factor Prothrombin Complex Concentrate: Review and Advances of Octaplex/Balfaxar (SCCM 2024) - "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. 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."

Review • Cardiovascular

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 • Gastrointestinal Disorder • Hematological Disorders • Immunology

Study of OCTAPLEX in Patients With Acute Major Bleeding on DOAC Therapy With Factor Xa Inhibitor (clinicaltrials.gov) - P3 | N=200 | Recruiting | Sponsor: Octapharma

Trial completion date • Trial primary completion date

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 • Transplantation

An innovative and accurate next-generation sequencing-based microsatellite instability detection method for colorectal and endometrial tumors. (PubMed, Lab Invest) - "This new NGS-based MSI detection method outperforms previously published methods (i.e. Idylla, OncoMate MSI Dx, and Foundation One® CDx). Although highly efficient, Octaplex CaBio-MSID requires validation in a larger independent series of different tumor types."

Biomarker • IO biomarker • Journal • Next-generation sequencing • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI

Twenty Years of Four-Factor Prothrombin Complex Concentrate: a Literature Review of Prospective Clinical Trials of Octaplex/Balfaxar (ASA 2023) - "Additionally, in a recent randomized, double-blind, phase III study, octaplex® was found to be non-inferior to the FDA-approved control 4F-PCC (Kcentra®, CSL Behring), achieving similar hemostatic efficacy, INR correction, and safety profile. Evidence from the octaplex® clinical development program over 20 years of use indicates that octaplex® is efficacious for multiple indications with a favorable safety profile. The clinical utility of octaplex® is also expanding with ongoing investigation in acute major bleeding in patients on DOAC therapy and in patients undergoing cardiac surgery."

Clinical • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Pediatrics

Hemostatic efficacy and safety of four-factor prothrombin complex concentrates for vitamin K antagonist reversal before urgent surgery: a double-blind, randomized, non-inferiority trial (ASA 2023) - "Introduction: The Phase 3 LEX-209 study tested for the non-inferiority of an investigational four-factor prothrombin complex concentrate (4F-PCC; Octaplex®, Octapharma) compared with the FDA-approved control 4F-PCC (Kcentra®, CSL Behring) for rapid reversal of vitamin K antagonist (VKA) anticoagulation before urgent surgery. The investigational 4F-PCC was non-inferior to the control 4F-PCC with regards to hemostatic efficacy for VKA reversal in patients who underwent urgent surgery with significant bleeding risk."

Clinical • Head-to-Head • Surgery • Cardiovascular • Gastrointestinal Disorder

Effect of PCC on Thrombin Generation among Patients on Factor Xa Inhibitors with Major Bleeding or Needing Urgent Surgery (GAUGE): Design and Rationale. (PubMed, TH Open) - "Clinicians have variable national and regional access to specific FXaI reversal agents such as andexanet alfa...Objective  GAUGE is a prospective observational study designed to measure the effects of four-factor PCC administration (Octaplex) on TGA parameters among patients with FXaI-associated bleeding or needing urgent surgery...Conclusion  Development of a viable and universally accessible FXaI bleed management strategy is crucial. GAUGE will provide in vivo data on the effects of PCC among patients with FXaI-associated bleeding."

Journal • Surgery • Cardiovascular

Octapharma's Prothrombin Complex Concentrate, Balfaxar, Receives FDA Approval For Warfarin Reversal in Urgent Surgery & Invasive Procedures (PRNewswire) - "Octapharma USA today announced that Balfaxar® (prothrombin complex concentrate, human-lans; marketed in Europe and Canada as octaplex®) has received U.S. Food and Drug Administration (FDA) approval for the urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with need for urgent surgery or invasive procedures....The FDA approval is supported by the clinical trial LEX-209 (ClinicalTrials.gov Identifier: NCT02740335)..."

sBLA • Genetic Disorders • Hematological Disorders • Hemophilia

Using heparin-calibrated assays to assess anti-factor Xa activity of factor Xa inhibitors (FXaI): a literature correlation analysis (ISTH 2023) - P3 | "LEX-210 (NCT04867837, Octapharma) will evaluate the hemostatic efficacy of a four-factor PCC (Octaplex®) in patients with acute major bleeding on FXaI and one of the main inclusion criteria is that patients must have a baseline anti-factor Xa (anti-Xa) activity equivalent to ≥100 ng/mL of FXaI. 8/57 screened articles contained relevant data. Correlation curves against FXaI-calibrated anti-Xa assays were obtained for heparin-calibrated assays, for different combinations of device/reagent/calibrator. The correlation curves and corresponding conversion table for a commonly used device (STA-R coagulation analyzer) and FXaI (apixaban) are shown (Figure 1/Table 1)."