What are the differences and similarities between Riastap (fibrinogen concentrate) and Fibryga (fibrinogen concentrate) in treating congenital fibrinogen deficiency?

Differences and Similarities Between RiaSTAP and Fibryga for Congenital Fibrinogen Deficiency

Both RiaSTAP and Fibryga are effective fibrinogen concentrates for treating congenital fibrinogen deficiency, but Fibryga has a higher factor XIII content (0.2 IU per mg fibrinogen) which may provide superior clot firmness properties. 1, 2

Similarities

• Both are human fibrinogen concentrates derived from pooled plasma and undergo virus inactivation/elimination processes 1
• Both are reconstituted to a concentration of 20 g/L when prepared according to manufacturers' guidelines 1
• Both products are licensed for use in congenital hypofibrinogenemia in the UK 1
• Both increase plasma fibrinogen levels by approximately 0.2-0.3 g/L for every gram of concentrate administered 1
• Both demonstrate comparable pharmacokinetic profiles with similar half-life and maximum concentration parameters 3
• Both products have demonstrated efficacy in on-demand treatment of bleeding episodes and surgical prophylaxis in patients with congenital fibrinogen deficiency 4, 5
• Neither product requires cross-matching before administration 1

Key Differences

• Factor XIII content: Fibryga contains a higher concentration of factor XIII (0.2 IU factor XIII per mg fibrinogen) compared to RiaSTAP 1, 2
• Clot firmness: In-vitro studies have shown increased maximum clot firmness with Fibryga compared to RiaSTAP, likely due to the higher factor XIII content 1
• Pharmacokinetics: Fibryga demonstrates a larger area under the curve (AUCnorm) and slower clearance compared to RiaSTAP, suggesting potentially longer-lasting effect in circulation 3
• Licensing: While RiaSTAP was initially the only globally available fibrinogen concentrate licensed for congenital hypofibrinogenemia, Fibryga is now also licensed for management of uncontrolled severe hemorrhage in patients with acquired hypofibrinogenemia during surgery 1

Clinical Efficacy

• Both products have demonstrated high success rates in treating bleeding episodes in patients with congenital fibrinogen deficiency 4, 5
• In clinical studies, Fibryga showed treatment success rates of 95.7-100% for on-demand treatment of bleeding episodes as assessed by investigators and independent committees 4, 5
• Fibryga has demonstrated efficacy in pediatric patients with congenital fibrinogen deficiency, with 100% treatment success for bleeding episodes and surgical prophylaxis 6
• Both products significantly increase maximum clot firmness (MCF) as measured by thromboelastometry, with mean increases of 5.8-6.5 mm after administration 4, 5

Safety Profile

• Both products have favorable safety profiles with low risk of thrombotic events 4, 5, 3
• Neither product has been associated with development of neutralizing antibodies in clinical studies 5
• Both undergo rigorous pathogen safety measures including solvent detergent treatment and nanofiltration 7
• Fibryga has demonstrated stability for at least three years when stored at room temperature 7

Practical Considerations

• For treatment of bleeding episodes in congenital fibrinogen deficiency, a typical dose is around 60-70 mg/kg 4, 5
• For surgical prophylaxis, higher doses may be required (median dose around 85-95 mg/kg per surgery) 4, 5
• The higher factor XIII content in Fibryga may provide additional benefit in improving clot firmness, which could be advantageous in severe bleeding situations 1, 2

Pitfalls and Caveats

• Despite theoretical concerns about thrombotic risk with fibrinogen administration, clinical studies have shown low incidence of thrombotic events with both products 4, 5, 3
• Laboratory methods to measure fibrinogen concentration may have methodological issues, particularly in the presence of artificial colloids, which can affect dosing decisions 2
• Single-dose administration is often sufficient for treating bleeding episodes (91.3% of cases in one study of Fibryga) 4