Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients
Lissitchkov T, Madan B, Khayat CD, Zozulya N, Ross C, Karimi M, Kavakli K, De Angulo GR, Almomen A, Subramanian K, D’Souza F, Viswabandya A, Hoorfar H, Schwartz BA, Solomon C, Knaub S, Peyvandi F. J Thromb Haemost. 2020;18:815-824.
Introduction:
• Human fibrinogen concentrates (HFC) are recognized as the preferred choice for fibrinogen replacement in the treatment of bleeding in patients with congenital fibrinogen deficiency (CFD)*
• HFC offers multiple advantages over fresh frozen plasma (FFP) and cryoprecipitate: faster preparation and administration (no thawing, no blood matching, low infusion volume), standardized dosing, no risk of volume overload, greater purity, reduced risk of pathogen transmission—plus an excellent safety profile
• Fibryga® is a plasma-derived, double virus-inactivated/eliminated HFC indicated for the treatment of acute bleeding episodes in adults and children with CFD, including afibrinogenemia and hypofibrinogenemia. Fibryga is not indicated for dysfibrinogenemia
Methods:
• FORMA-02 was a prospective, multicenter, open-label, uncontrolled Phase 3 efficacy and safety study conducted in 25 evaluable patients with afibrinogenemia across 12 centers in the US, Europe, Asia and the Middle East from October 2014 through February 2018
• Hemostatic efficacy of fibryga for treatment of bleeding episodes (BEs) or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a 4-point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined
• Dosing was individually calculated for each patient based on baseline fibrinogen activity levels
• After each infusion, patients were monitored for ≥3 days for minor bleeding or minor surgery or ≥7 days for major bleeding or major surgery. Patients treated on-demand for bleeding were monitored for a 30-day safety follow-up
*Fibryga is not currently indicated for perioperative prophylaxis.
Indications and Usage
Fibryga® is a human fibrinogen concentrate indicated for the treatment of acute bleeding episodes in adults and children with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. Fibryga is not indicated for dysfibrinogenemia.
Warnings and Precautions
Monitor patients for early signs of hypersensitivity or allergic reactions. If necessary, discontinue administration and institute appropriate treatment. Thrombotic events have been reported in patients receiving Fibryga. Treatment with human fibrinogen concentrate has been associated with thrombosis at target plasma fibrinogen levels that were below 150 mg/dL. The thrombotic risks may be greater when the target fibrinogen plasma level is 150 mg/dL. Weigh the benefits of administration versus the risks of thrombosis.
Fibryga is made from pooled human plasma. Products made from human plasma may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
Please see accompanying full Prescribing Information.
Fibryga Achieved 98.9% Success for On-demand Treatment of Bleeding (Assessed by IDMEAC)
Rapid Increases in Fibrinogen Levels Achieved in All Patients
Maximum Plasma Fibrinogen Increases Were Reached at 1 or 3 Hours Postinfusion
• Hemoglobin levels remained stable following fibryga administration for the majority of patients
INFUSION,
event
Clot Strength Increased in Every Patient Within 1 Hour of Infusion
The change in MCF from baseline showed a statistically significant increase after treatment, and was in agreement with the investigators and IDMEAC efficacy rating
Indications and Usage
Fibryga® is a human fibrinogen concentrate indicated for the treatment of acute bleeding episodes in adults and children with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. Fibryga is not indicated for dysfibrinogenemia.
Contraindications
Fibryga is contraindicated in individuals who have manifested severe immediate hypersensitivity reactions, including anaphylaxis, to Fibryga or its components.
The most serious adverse reactions that may be observed with Fibryga are thromboembolic episodes and anaphylactic type reactions. The most common adverse reactions observed in more than one subject in clinical studies with Fibryga (> 5% of subjects) were nausea, vomiting, pyrexia (fever) and thrombocytosis.
Please see accompanying full Prescribing Information.
Fibryga Demonstrated a Favorable Safety Profile
• In total, 91 adverse events (AEs) occurred in 19 patients
– 43 AEs were treatment-emergent – 3 AEs in three patients were considered possibly related to treatment, including one moderate case of thrombosis
There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of
Important Safety Information
Warnings and Precautions
Monitor patients for early signs of hypersensitivity or allergic reactions. If necessary, discontinue administration and institute appropriate treatment. Thrombotic events have been reported in patients receiving Fibryga®. Treatment with human fibrinogen concentrate has been associated with thrombosis at target plasma fibrinogen levels that were below 150 mg/dL. The thrombotic risks may be greater when the target fibrinogen plasma level is 150 mg/dL. Weigh the benefits of administration versus the risks of thrombosis.
Please see accompanying full Prescribing Information.
Fibrinogen (Human)
Summary
Fibryga was highly efficacious for on-demand treatment of bleeding in patients with CFD
• 99% treatment success for on-demand treatment
• Increase in clot strength and fibrinogen levels within 1 hour of infusion
• Favorable safety profiles, with no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antibodies
FORMA-02 IS THE LARGEST PROSPECTIVE INTERVENTIONAL STUDY IN CFD TO DATE, and the first Phase III study in this disease setting to use objective 4-point criteria to assess hemostatic efficacy.
Important Safety Information
Contraindications
Fibryga® is contraindicated in individuals who have manifested severe immediate hypersensitivity reactions, including anaphylaxis, to Fibryga or its components.
The most serious adverse reactions that may be observed with Fibryga are thromboembolic episodes and anaphylactic type reactions. The most common adverse reactions observed in more than one subject in clinical studies with Fibryga (> 5% of subjects) were nausea, vomiting, pyrexia (fever) and thrombocytosis.
Warnings and Precautions
Monitor patients for early signs of hypersensitivity or allergic reactions. If necessary, discontinue administration and institute appropriate treatment. Thrombotic events have been reported in patients receiving Fibryga®. Treatment with human fibrinogen concentrate has been associated with thrombosis at target plasma fibrinogen levels that were below 150 mg/dL. The thrombotic risks may be greater when the target fibrinogen plasma level is 150 mg/dL. Weigh the benefits of administration versus the risks of thrombosis.
Fibryga is made from pooled human plasma. Products made from human plasma may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
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For all inquiries relating to drug safety, or to report adverse events, please contact our local Drug Safety Officer: Tel: 201-604-1137 | Cell: 201-772-4546 | Fax: 201-604-1141 or contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see accompanying full Prescribing Information.