Fibryga (fibrinogen concentrate (human)) / Octapharma - LARVOL DELTA

Fibrinogen concentrate versus cryoprecipitate for bleeding in cardiac surgery patients stratified by surgery risk in the phase 3 fibres Study (ASH 2025) - P3 | "Moreover, FC was non-inferiorto cryoprecipitate in high-risk surgical patients when excluding the most extreme atypical clinical casescharacterized by catastrophic bleeding and massive transfusion. These findings reinforce the mainoutcomes from the FIBRES study and support the use of FC for management of bleeding in cardiacsurgical patients with acquired hypofibrinogenemia."

Clinical • P3 data • Surgery • Acute Kidney Injury • Anesthesia • Cardiovascular • Renal Disease • Ventricular Tachycardia

Post-Marketing Observational Study of the Safety and Efficacy of Fibrinogen Concentrate in Congenital Fibrinogen Deficiency in Patients of All Ages (ASH 2023) - P | "Results of HFC safety and efficacy will be continually monitored throughout the study. Completion is expected Q4 2027."

Clinical • Observational data • P4 data • Cardiovascular • Hematological Disorders • Pediatrics • Thrombosis

Prophylaxis and Treatment of Bleeding or Thrombosis with Fibrinogen Concentrate (Fibryga) in Patients with Congenital Hypofibrinogenemia or Dysfibrinogenemia (ASH 2023) - "The post procedural bleeding noted in one patient may have been due to inadequate fibrinogen concentration or other comorbid conditions. Further clinical studies are needed to determine the role of FIBRGYA and other HFC in the treatment of patients with CFD, especially those with CD."

Clinical • Cardiovascular • Diabetes • Hematological Disorders • Hypertension • Immunology • Metabolic Disorders • Peripheral Arterial Disease • Thrombosis • Type 2 Diabetes Mellitus

A Single Center Approach to Managing Hospitalized Patients with Quantitative Fibrinogen Deficiency That Cost-Saving and Maintains High-Quality, Evidence-Based Care (ASH 2024) - "Guidelines recommend using cryoprecipitate (CP) or fibrinogen concentrates (FC) for replacement. Of the two FC with equal efficacy, using FiB instead of RiA is more cost-saving (36%) to our institution. It highlights the need for a larger study of healthcare utilization and cost-effectiveness analysis paired with measurable outcomes of both FC."

Clinical • HEOR • Cardiovascular • Hematological Disorders • Infectious Disease • Pediatrics

Title: Real-World Utilization of Human Fibrinogen Concentrate in Managing Bleeding in Adult and Pediatric Patients: A Retrospective Study (ASH 2024) - "The existing findings provide justification for the adoption of human fibrinogen concentrate in many clinical scenarios, including both surgical and nonsurgical hemorrhage. The practical benefits and predictable effects of human fibrinogen concentrate in place of standard treatments highlight its potential to not only enhance patient outcomes but also provide for optimized clinical workflows."

Real-world • Real-world evidence • Retrospective data • Hematological Disorders • Hepatology • Mood Disorders • Pediatrics • Postpartum Hemorrhage

CS203. What's New in Perioperative Bleeding Management: Critical Discussion (Non-CME) (ASA 2025) - "Oliver Hegener (Octapharma). This interactive discussion will explore real-world experiences and evidence-based insights on the use of Fibryga (fibrinogen concentrate) in bleeding management, particularly in cardiac surgery."

Cardiovascular

Fibrinogen concentrate versus cryoprecipitate for bleeding in cardiac surgery patients stratified by surgery risk (ASA 2025) - P3 | "In this post-hoc analysis, FC was shown to be superior to cryoprecipitate with regard to number of blood components transfused in patients assessed as moderate surgical risk. This subgroup represents the large majority (greater than 85%) of patients undergoing cardiac surgery and requiring fibrinogen supplementation in the FIBRES study. These findings support the main outcomes from the FIBRES study and support the use of FC for management of bleeding in patients with acquired hypofibrinogenemia in cardiac surgery."

Clinical • Surgery • Acute Kidney Injury • Cardiovascular • Renal Disease • Ventricular Tachycardia

Evaluating the Use of Human Fibrinogen Concentrate and Cryoprecipitate in Orthotopic Liver Transplantation (ASA 2025) - "In this case series, increased dose of Fibryga was associated with increased cryoprecipitate volume transfusions intraoperatively suggesting higher utilization of cryoprecipitate and other blood products during severe intraoperative coagulopathy may necessitate Fibryga administration as off label use for acquired hypofibrogenemia. Data is limited by single institution experience and small sample size. Further research needed to fully evaluate Fibryga as an adjunct to cryoprecipitate administration in OLT."

Anesthesia • Cardiovascular • Hematological Disorders • Hepatology • Immunology • Liver Failure • Thrombosis • Transplantation

Single Institution Experience Using Intraoperative Human Fibrinogen Concentrate Fibryga in Orthotopic Liver Transplantation - A Case Series (WTC 2025) - "In this case series, human fibrinogen concentrate Fibryga was administered intraoperatively to 16 patients undergoing OLT. High rate of biliary complications may be due to ischemic injury from intraoperative hemodynamic instability. Formal clinical trials must be performed to fully evaluate the safety and effectiveness of Fibryga administration in OLT."

Clinical • Cardiovascular • Hematological Disorders • Hepatology • Liver Failure • Thrombosis • Transplantation

FORMA-07: Safety and Efficacy of Fibryga in Congenital Fibrinogen Deficiency (clinicaltrials.gov) - P=N/A | N=7 | Terminated | Sponsor: Octapharma | N=25 ➔ 7 | Trial completion date: Oct 2027 ➔ May 2025 | Recruiting ➔ Terminated | Trial primary completion date: Oct 2027 ➔ May 2025; FORMA-07 was initiated as a requirement imposed by the U.S. FDA as part of Octapharma's regulatory obligations. After approving Fibryga for treatment of acquired fibrinogen deficiency in 2024, FDA has agreed that the study may now be discontinued.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination

SY105. Beyond the Bleed: Revolutionizing Precision in Hemorrhage Management (non-CME) (ASA 2024) - "Propel your bleeding management practice to new heights! Octapharma, Annual Meeting Supporter"

Cardiovascular • Hematological Disorders • Obstetrics

Cancelled: A Real-World, Retrospective, Observational Study of Fibrinogen Concentrate in Patients With Acute Gastrointestinal Hemorrhage and Fibrinogen Deficiency: Sub-Analysis of the FORMA-10 Study (AABB 2024) - P=N/A | "Among these patients, 17 (81.0%) received concomitant medication, with 6 (35.3%) receiving tranexamic acid. This real-world data shows that FC was successful for on-demand treatment of non‑surgical GI bleeding, with a favorable safety profile. These findings provide valuable insights to aid clinicians in making informed decisions regarding the use of FC for the management of GI bleeding."

Observational data • Real-world • Real-world evidence • Retrospective data • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders

Are all fibrinogen concentrates the same? The effects of two fibrinogen therapies in an afibrinogenemic patient and in a fibrinogen deficient plasma model. A clinical and laboratory case report. (PubMed, Front Med (Lausanne)) - "Our report offers insights into the differential effects of these concentrates, at the clot level, according to the variable constituents of each product, thereby emphasizing that the choice of fibrinogen concentrate can influence the stability of a clot in vivo. Whether this alters clinical efficacy is yet to be understood."

Journal • Hematological Disorders • Mood Disorders

PROPHYLACTIC OR POST-TRAUMATIC TREATMENT OF HYPOFIBRINOGENEMIA AND DYSFIBRINOGENEMIA WITH FIBRGYA IN EIGHT CLINICAL CASES (THSNA 2024) - "Methods/ We present eight clinical cases of patients with hypo- or dysfibrinogenemia that were effectively treated with a pooled, plasma-derived fibrinogen concentrate (FIBRYGA) either prophylactically for elective or urgent surgery, or post-traumatic injury. For the majority (86%) of our patients described here with CH and CD, FIBRYGA was well tolerated and effective in preventing post procedural or post traumatic bleeding complications. The post procedural bleeding noted in one patient may have been due to inadequate fibrinogen concentration or other comorbid conditions. Further clinical studies are needed to determine the role of FIBRGYA and other HFC in the treatment of patients with CFD."

Clinical • Cardiovascular • Diabetes • Hematological Disorders • Hypertension • Immunology • Metabolic Disorders • Pain • Peripheral Arterial Disease • Type 2 Diabetes Mellitus

Forma-10 sub-analysis: a real-world, retrospective, observational study of fibrinogen concentrate in patients with trauma-related bleeding and fibrinogen deficiency (ISICEM 2024) - "This contemporary, real -life data set indicates that fibrinogen concentrate is successfully used in the management of non -surgical trauma -related bleeding in a European healthcare setting."

Observational data • Real-world • Real-world evidence • Retrospective data • Mood Disorders

Safety and Efficacy of Fibryga in Congenital Fibrinogen Deficiency (clinicaltrials.gov) - P=N/A | N=25 | Recruiting | Sponsor: Octapharma

Trial completion date • Trial primary completion date

Comparison of coagulation parameters associated with fibrinogen concentrate and cryoprecipitate for treatment of bleeding in patients undergoing cytoreductive surgery for pseudomyxoma peritonei: Subanalysis from a randomized, controlled phase 2 study. (PubMed, Health Sci Rep) - "Patients with PE experienced a disproportionate VWF rise following cryoprecipitate administration, whereas patients developing DVT displayed a procoagulant status before and following surgery. Preoperative testing may allow these patients to be identified."

Journal • P2 data • Surgery • Cardiovascular • Hematological Disorders • Pulmonary Embolism • Respiratory Diseases • Thrombosis • Venous Thromboembolism

Differences in coagulation-relevant parameters: Comparing cryoprecipitate and a human fibrinogen concentrate. (PubMed, PLoS One) - "The tested HFC is a more reliable fibrinogen and FXIII source for accurate dosing compared with cryoprecipitate. Cryoprecipitate appears considerably less predictable for bleeding management due to wide variation in pro- and anticoagulation factors, the presence of PMPs, and the potential to elevate VWF and FVIII to prothrombotic levels."

Journal

Management of Dysfibrinogenemia in a Pediatric Patient Undergoing Scoliosis Repair: Case Report (ISTH 2023) - "She received replacement prior to surgery with Human Fibrinogen concentrate, (Fibryga®), with goal fibrinogen activity >150 during the immediate post-operative period...She was started on thromboprophylaxis with enoxaparin 48 hours after surgery, until date of discharge... A 16-year-old female with idiopathic scoliosis was diagnosed with dysfibrinogenemia, after pre-operative testing revealed prolonged PT (19.9 seconds), elevated INR (1.7) and prolonged aPTT (36.6 seconds). Her bleeding score was 3, and her history significant for heavy menstruation and having raccoon eye as a child, after mild scalp trauma. No notable prior thrombotic events or contributory family history."

Clinical • Pediatrics

Real-World Experience with a Human Fibrinogen Concentrate: Clinical Data From Adult and Pediatric Patients Requiring Fibrinogen For Bleeding Control and Prevention. (PubMed, J Clin Pharmacol) - "Fibrinogen concentrate demonstrated favorable effectiveness and safety across age groups. This study contributes to evidence supporting fibrinogen concentrate for bleeding control/prevention in real-world clinical practice, particularly for patients with acquired fibrinogen deficiency."

Clinical data • Journal • Real-world • Real-world evidence • Cardiovascular • Hematological Disorders • Pediatrics • Postpartum Hemorrhage

Comparison of Fibrinogen Concentrate and Cryoprecipitate in Pediatric Cardiac Surgery Patients (clinicaltrials.gov) - P4 | N=30 | Completed | Sponsor: University of Virginia | Recruiting ➔ Completed | Trial completion date: Dec 2023 ➔ May 2023 | Trial primary completion date: Aug 2023 ➔ Mar 2023

Surgery • Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • Pediatrics

Procoagulation status and coagulation factor levels in patients experiencing thromboembolic events in a randomised, controlled Phase 2 study of fibrinogen concentrate and cryoprecipitate for treatment of bleeding in patients undergoing major cytoreductive surgery (Euroanaesthesia 2023) - "Patients received cryoprecipitate (N=23) or HFC (N=21). No patients in the HFC group developed TEEs. In the cryoprecipitate group, 2 patients experienced deep vein thrombosis (DVT) and 5 patients experienced pulmonary embolism (PE)."

Clinical • P2 data • Surgery • Cardiovascular • Hematological Disorders • Pulmonary Embolism • Respiratory Diseases • Venous Thromboembolism

Potential for prolongation of fibrinogen concentrates post-reconstitution. (PubMed, Transfus Apher Sci) - "Fibryga® can be stored at 2-8 °C post-reconstitution for up to one week with no loss in functional fibrinogen activity based on Clauss fibrinogen assay. Further studies with other fibrinogen concentrate formulations and clinical in vivo studies may be warranted."

Journal

Efficacy and safety of fibrinogen concentrate for perioperative prophylaxis of bleeding in adult, adolescent, and pediatric patients with congenital fibrinogen deficiency: FORMA-02 and FORMA-04 clinical trials. (PubMed, Transfusion) - "In adults/adolescents and pediatric patients with fibrinogen deficiency, HFC treatment for hemostatic management during/after minor and major surgery was successful, with efficacy comparable across the different age groups."

Journal • Hematological Disorders • Pediatrics

Analysis of fibrinogen concentrate pharmacokinetics and dosing for bleeds and surgery in adults, adolescents, and children with congenital afibrinogenaemia and hypofibrinogenaemia. (PubMed, Haemophilia) - "As expected, HFC PK differed between adults/adolescents and children. However, with the higher doses given to children, HFC showed similar efficacy across age groups. Dose adaptation based on age groups appears recommendable."

Journal • PK/PD data • Hematological Disorders