Clinical trials of fibryga® in AFD

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Efficacy & Safety
Clinical trials of fibryga® in AFD

Key clinical studies supporting the use of fibryga® in AFD

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Summary of fibryga® clinical trials in AFD

In patients with AFD, key clinical studies of fibryga® are the FORMA-05 and FIBRES trials.

Design
 
 Treatment 
 Sample size
 
 Study population 


 Primary objective
 


 
 Primary endpoint results 

 


 Other efficacy measures 

 


 Safety FORMA-05 ¹ , Prospective, randomised, controlled, open-label, single-centre phase II study or guided by a ROTEM-based protocol 4g of fibrinogen concentrate2 pools of cryoprecipitate; (43 per-protocol)

 45 patients aged ≥18 years undergoing CRS for PMP
 Bleeding patients of fibryga® with active control (cryoprecipitate) in bleeding patients who developed AFD during surgery, measured as composite of intra-operative and post-operative haemostatic efficacy, assessed by IDMEAC To compare the overall haemostatic efficacy All patients receiving fibryga® (95% CI: 83.9-100.0, n = 21) or cryoprecipitate (84.6-100.0, n = 22) achieved haemostatic success. (p=0.01; post hoc analysis)
 Haemostatic efficacy
 Fibryga® was non-inferior to active control for overall haemostatic efficacy Intra-operative efficacy was excellent or good in 95.2% and 72.7% patients in the fibryga® and active control groups, respectively (IDMEAC) 
 

 Haemostatic efficacyTimely access and administration F ibryga® was delivered to the operating theatre a mean of 46 minutes earlier than active control (except for thromboembolic events which were only seen in the active control group) All AEs were treatment-emergent; none were related to study drug administration

 Both fibryga® and active control demonstrated comparable safety profiles FIBRES ² Prospective, randomised, controlled, multicentre, single-blinded phase III study , infused over ~10 minutes or infused according to local practice 4g of fibrinogen concentrate10 units of cryoprecipitate, 827 randomised patients; 735 ( fibryga®; 363 cryoprecipitate) treated and included in primary analysis and safety population 372 Patients ≥18 years with attributed to acquired hypofibrinogenaemia clinically significant CPB bleeding to active control for the treatment of bleeding related to hypofibrinogenaemia, as measured by total number of allogeneic blood products administered during first 24h after cardiac surgery
 To demonstrate non-inferiority of fibryga® The least-squares (LS) mean number of blood products transfused during the first 24 hours after surgery was 16.3 units in the fibryga® group and 17.0 units in the cryoprecipitate group. Based on these findings, (p<0.001; one-sided test) Blood products used
 fibryga® was shown to be non-inferior to active control ibryga® was non-inferior to active control for total number of red blood cells, platelets and plasma transfused within 24 hours after surgery ibryga® was non-inferior to active control for mean number of blood products transfused from surgery to post-operative day 7 (22.5 units vs 22.3, respectively; p<0.001) Individual blood products transfused within 24 hours
Blood products transfused within 7 days
 FF with reference to treatment-emergent AEs and other outcomes Deaths occurred in both treatment groups and the rates observed were not significantly different between the groups (35 deaths (9.4%) in the fibryga® group and 27 (7.4%) in the cryoprecipitate group; unadjusted HR: 1.28 [95% CI, 0.77, 2.12]; p=0.35) Fibryga® and active control showed similar safety profiles AE, adverse event; AFD, acquired fibrinogen deficiency; CI, confidence interval; CPB, cardiopulmonary bypass; CRS, cytoreductive surgery; IDMEAC, Independent Data Monitoring and Endpoint Adjudication Committee; PMP, pseudomyxoma peritonei; ROTEM, rotational thromboelastometry.
Design
 
 Treatment 
 Sample size
 
 Study population 


 Primary objective
 


 
 Primary endpoint results 

 


 Other efficacy measures 

 


 Safety FORMA-05 ¹ , Prospective, randomised, controlled, open-label, single-centre phase II study or guided by a ROTEM-based protocol 4g of fibrinogen concentrate2 pools of cryoprecipitate; (43 per-protocol)

 45 patients aged ≥18 years undergoing CRS for PMP
 Bleeding patients of fibryga® with active control (cryoprecipitate) in bleeding patients who developed AFD during surgery, measured as composite of intra-operative and post-operative haemostatic efficacy, assessed by IDMEAC To compare the overall haemostatic efficacy All patients receiving fibryga® (95% CI: 83.9-100.0, n = 21) or cryoprecipitate (84.6-100.0, n = 22) achieved haemostatic success. (p=0.01; post hoc analysis)
 Haemostatic efficacy
 Fibryga® was non-inferior to active control for overall haemostatic efficacy Intra-operative efficacy was excellent or good in 95.2% and 72.7% patients in the fibryga® and active control groups, respectively (IDMEAC) 
 

 Haemostatic efficacyTimely access and administration F ibryga® was delivered to the operating theatre a mean of 46 minutes earlier than active control (except for thromboembolic events which were only seen in the active control group) All AEs were treatment-emergent; none were related to study drug administration

 Both fibryga® and active control demonstrated comparable safety profiles FIBRES ² Prospective, randomised, controlled, multicentre, single-blinded phase III study , infused over ~10 minutes or infused according to local practice 4g of fibrinogen concentrate10 units of cryoprecipitate, 827 randomised patients; 735 ( fibryga®; 363 cryoprecipitate) treated and included in primary analysis and safety population 372 Patients ≥18 years with attributed to acquired hypofibrinogenaemia clinically significant CPB bleeding to active control for the treatment of bleeding related to hypofibrinogenaemia, as measured by total number of allogeneic blood products administered during first 24h after cardiac surgery
 To demonstrate non-inferiority of fibryga® The least-squares (LS) mean number of blood products transfused during the first 24 hours after surgery was 16.3 units in the fibryga® group and 17.0 units in the cryoprecipitate group. Based on these findings, (p<0.001; one-sided test) Blood products used
 fibryga® was shown to be non-inferior to active control ibryga® was non-inferior to active control for total number of red blood cells, platelets and plasma transfused within 24 hours after surgery ibryga® was non-inferior to active control for mean number of blood products transfused from surgery to post-operative day 7 (22.5 units vs 22.3, respectively; p<0.001) Individual blood products transfused within 24 hours
Blood products transfused within 7 days
 FF with reference to treatment-emergent AEs and other outcomes Deaths occurred in both treatment groups and the rates observed were not significantly different between the groups (35 deaths (9.4%) in the fibryga® group and 27 (7.4%) in the cryoprecipitate group; unadjusted HR: 1.28 [95% CI, 0.77, 2.12]; p=0.35) Fibryga® and active control showed similar safety profiles AE, adverse event; AFD, acquired fibrinogen deficiency; CI, confidence interval; CPB, cardiopulmonary bypass; CRS, cytoreductive surgery; IDMEAC, Independent Data Monitoring and Endpoint Adjudication Committee; PMP, pseudomyxoma peritonei; ROTEM, rotational thromboelastometry.

FORMA-05 trial

Study design1

  • A prospective, randomised, controlled, open-label, single-centre phase II study to assess the haemostatic efficacy and safety of fibryga® versus active control (cryoprecipitate) in bleeding patients aged ≥18 years undergoing cytoreductive surgery (CRS) for pseudomyxoma peritonei (PMP)

  • This study was used as a model for surgical bleeding and provides the evidence for the fibryga® licence indication in AFD

  • Treatment with fibrinogen replacement therapy was guided by a ROTEM-based protocol

  • 45 patients were included in the full analysis set (FAS)/safety population, and 43 in the per-protocol population (primary analysis population) 

Primary objective1
To compare the overall haemostatic efficacy of fibryga® with active control (cryoprecipitate) in bleeding patients who developed AFD during surgery

Results: Overall and intra-operative haemostatic efficacy1

  • A post-hoc analysis showed that fibryga® was non-inferior to active control for overall haemostatic efficacy (p=0.01; Farrington–Manning test) (see Table below)

Overall haemostatic efficacy ratings in the FORMA-05 trial1

Two-point efficacy scale*
 Success Failure Fibryga (n=21)
n (%) [95% CI] ® 21 (100)[83.9-100.0] 0 Cryoprecipitate (n=22)
n (%) [95% CI] 22 (100)[84.6-100.0] 0 Per-protocol analysis (N=43). Patients undergoing PMP surgery with predicted intra-operative blood loss ≥2 L received fibryga® (4g) or cryoprecipitate (two pools of 5 units, containing approximately 4.0–4.6g fibrinogen), repeated as needed. Efficacy rating of excellent or good indicated success; efficacy rating of moderate or none indicated failure. CI, confidence interval; IDMEAC, Independent Data Monitoring and Endpoint Adjudication Committee. Adapted from Roy et al, 2020. ¹
Two-point efficacy scale*
 Success Failure Fibryga (n=21)
n (%) [95% CI] ® 21 (100)[83.9-100.0] 0 Cryoprecipitate (n=22)
n (%) [95% CI] 22 (100)[84.6-100.0] 0 Per-protocol analysis (N=43). Patients undergoing PMP surgery with predicted intra-operative blood loss ≥2 L received fibryga® (4g) or cryoprecipitate (two pools of 5 units, containing approximately 4.0–4.6g fibrinogen), repeated as needed. Efficacy rating of excellent or good indicated success; efficacy rating of moderate or none indicated failure. CI, confidence interval; IDMEAC, Independent Data Monitoring and Endpoint Adjudication Committee. Adapted from Roy et al, 2020. ¹

  • Intra-operative efficacy was rated by the IDMEAC as excellent or good in 95.2% and 72.7% of patients in the fibryga® and active control groups (per-protocol population), respectively (see Table below)

Intra-operative haemostatic efficacy ratings in the FORMA-05 trial1

Four-Point Efficacy Scale [%] Excellent Good Moderate None Fibryga (n=21) ® 61.9 33.3 4.8 0 Cryoprecipitate (n=22) 50.0 22.7 27.3 0 Per-protocol analysis (N = 43). IDMEAC, Independent Data Monitoring and Endpoint Adjudication Committee. Adapted from Roy et al, 2020. ¹
Four-Point Efficacy Scale [%] Excellent Good Moderate None Fibryga (n=21) ® 61.9 33.3 4.8 0 Cryoprecipitate (n=22) 50.0 22.7 27.3 0 Per-protocol analysis (N = 43). IDMEAC, Independent Data Monitoring and Endpoint Adjudication Committee. Adapted from Roy et al, 2020. ¹

Results: Timely access and administration with fibryga®1

  • Fibryga® was delivered to the operating theatre a mean of 46 minutes earlier than active control

  • As a result, the mean time between randomisation and the start of the initial infusion was 24 minutes shorter for the fibryga® group (p<0.0001)

Since the FORMA-05 trial, in our continued commitment to improving user experience, the transfer device supplied with fibryga® has transitioned from Octajet® to Nextaro®, facilitating a simplified reconstitution process.3

Combined with its room temperature storage meaning that fibryga® can be co-localised at the point of need,3 UK centres can achieve even faster time to administration than those seen in clinical trials.

Results: Fibryga® safety profile in the FORMA-05 trial1

  • Overall, both fibryga® and active control (cryoprecipitate) demonstrated comparable safety profiles, except the prevalence of thromboembolic events which were only seen in the active control group (see Figure below)

  • All AEs were treatment-emergent, and none were assessed as related to study drug administration

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Summary of AEs in the FORMA-05 trial1

225 228 222 214 2 12 Number of AEs 1 6 0 2 1 0 0 17 1 0 0 250 50 100 150 200 AE Mild AE Moderate AE Severe AE Probably or possibly
treatment-related AE AE leading to
withdrawal SAE Death Fibryga® (n=22) Cryoprecipitate (n=23) ¹ Safety population (N=45). A total of 225 AEs occurred in 22 patients (100%) in the fibryga® group and 228 AEs occurred in 23 patients (100%) in the cryoprecipitate group. 23 AEs in 18 patients were classed as SAEs. Of these, 6 were in the fibryga® group and 17 were in the cryoprecipitate group. No thromboembolic events were observed in the fibryga® group. In the cryoprecipitate group, 7 patients (30.4%) experienced 7 thromboembolic events (5 patients with pulmonary embolism and 2 patients with deep vein thrombosis) between post-operative days 4 and 11. There was a single death during the study. This death occurred post-operatively in a patient in the cryoprecipitate group who experienced a gastrointestinal anastomotic leak on post-operative day 10. This event was deemed unrelated to study drug administration. No other AEs led to discontinuation of a patient in the study. Adapted from Roy et al, 2020.
225 228 222 214 2 12 Number of AEs 1 6 0 2 1 0 0 17 1 0 0 250 50 100 150 200 AE Mild AE Moderate AE Severe AE Probably or possibly
treatment-related AE AE leading to
withdrawal SAE Death Fibryga® (n=22) Cryoprecipitate (n=23) ¹ Safety population (N=45). A total of 225 AEs occurred in 22 patients (100%) in the fibryga® group and 228 AEs occurred in 23 patients (100%) in the cryoprecipitate group. 23 AEs in 18 patients were classed as SAEs. Of these, 6 were in the fibryga® group and 17 were in the cryoprecipitate group. No thromboembolic events were observed in the fibryga® group. In the cryoprecipitate group, 7 patients (30.4%) experienced 7 thromboembolic events (5 patients with pulmonary embolism and 2 patients with deep vein thrombosis) between post-operative days 4 and 11. There was a single death during the study. This death occurred post-operatively in a patient in the cryoprecipitate group who experienced a gastrointestinal anastomotic leak on post-operative day 10. This event was deemed unrelated to study drug administration. No other AEs led to discontinuation of a patient in the study. Adapted from Roy et al, 2020.

FIBRES trial

Study design:2

  • A prospective, randomised, controlled, multicentre, single-blinded phase III study to assess the haemostatic efficacy of fibryga® against an active control (cryoprecipitate) in patients ≥18 years with clinically significant post-cardiopulmonary bypass (CPB) bleeding attributed to acquired hypofibrinogenaemia

  • Of the 827 randomised patients, 735 (372 fibryga®; 363 cryoprecipitate) were treated and included in the primary analysis and safety population

Primary objective2
To demonstrate non-inferiority of fibryga® to active control, for the treatment of bleeding related to hypofibrinogenaemia, as measured by the total number of allogeneic blood products (red blood cells, pooled or apheresis platelets and plasma) administered during the first 24 hours after cardiac surgery

Results: Blood products used within 24 hours and within 7 days after surgery2

  • Patients in the fibrinogen concentrate arm received 4g fibryga® infused in approximately 10 minutes. Those in the active control group received an (approximate) equivalent dose of 10 units of cryoprecipitate (the standard dosage issued by Canadian Blood Services)

In , fibryganon-inferiority to cryoprecipitate ® demonstrated FIBRES
In , fibryganon-inferiority to cryoprecipitate ® demonstrated FIBRES

  • Based on these findings, fibryga® was shown to be non-inferior to active control (p<0.001; one-sided test) for the primary endpoint (see Table below)

Total blood products transfused within 24 hours after surgery in the FIBRES trial*2

Primary analysis population N LS mean Median (IQR) Per-protocol population † N LS mean Median (IQR) Fibryga ® 372 16.3 12.0 (5.5-22.0) 364 16.4 12.0 (6.0-22.0) Cryoprecipitate 363 17.0 14.0 (7.0-23.0) 361 16.9 14.0 (7.0-22.0) ®†² *Units of allogenic blood components counted as follows: each red blood cell unit = 1 unit, each 250ml plasma unit = 1 unit, each 500-mL plasma unit = 2 units, each platelet dose = 4 units. Least-squares (LS) mean number of blood products transfused during the first 24 hours after surgery was 16.3 units in the fibryga group and 17.0 units in the active control group. Per-protocol set excluded patients who did not undergo cardiac surgery with cardiopulmonary bypass, received the incorrect treatment, received less than 80% of the planned dose, or received the first treatment more than 24 hours after cardiopulmonary bypass. IQR, interquartile range; LS, least squares. Adapted from Callum et al, 2019.
Primary analysis population N LS mean Median (IQR) Per-protocol population † N LS mean Median (IQR) Fibryga ® 372 16.3 12.0 (5.5-22.0) 364 16.4 12.0 (6.0-22.0) Cryoprecipitate 363 17.0 14.0 (7.0-23.0) 361 16.9 14.0 (7.0-22.0) ®†² *Units of allogenic blood components counted as follows: each red blood cell unit = 1 unit, each 250ml plasma unit = 1 unit, each 500-mL plasma unit = 2 units, each platelet dose = 4 units. Least-squares (LS) mean number of blood products transfused during the first 24 hours after surgery was 16.3 units in the fibryga group and 17.0 units in the active control group. Per-protocol set excluded patients who did not undergo cardiac surgery with cardiopulmonary bypass, received the incorrect treatment, received less than 80% of the planned dose, or received the first treatment more than 24 hours after cardiopulmonary bypass. IQR, interquartile range; LS, least squares. Adapted from Callum et al, 2019.

  • Fibryga® was also non-inferior to active control for the total number of red blood cells, platelets and plasma transfused within 24 hours after surgery

Individual blood products transfused within 24 hours after surgery in the FIBRES trial2

12 10 8 6 4 2 0 RBC transfusions Platelet transfusions Plasma transfusions 3.3 3.3 9.1 9.7 3.9 4.1 LS mean transfusions within
24 hours after surgery Fibryga® (n=372) Cryoprecipitate (n=363) N=735. The LS mean number of blood products transfused from surgery start to post-operative day 7 was 22.5 units in the fibryga® group (n=372) and 22.3 units in the active control group (n=363), respectively; fibryga® was non-inferior to active control for this endpoint (p<0.001). LS, least squares; RBC, red blood cell. Adapted from Callum et al, 2019. ²
12 10 8 6 4 2 0 RBC transfusions Platelet transfusions Plasma transfusions 3.3 3.3 9.1 9.7 3.9 4.1 LS mean transfusions within
24 hours after surgery Fibryga® (n=372) Cryoprecipitate (n=363) N=735. The LS mean number of blood products transfused from surgery start to post-operative day 7 was 22.5 units in the fibryga® group (n=372) and 22.3 units in the active control group (n=363), respectively; fibryga® was non-inferior to active control for this endpoint (p<0.001). LS, least squares; RBC, red blood cell. Adapted from Callum et al, 2019. ²

Results: Fibryga® safety profile in the FIBRES trial2

  • Both fibryga® and active control (cryoprecipitate) showed similar safety profiles with reference to treatment-emergent AEs and other measured outcomes at 28-day follow-up (i.e., duration of intubation, intensive care unit stay, and hospital stay)

Summary of AEs in the FIBRES trial2

AE 623 673 264 224 SAE Thromboembolic events Death Acute kidney injury Hepatobiliary disorders 0 800 100 200 300 400 500 600 700 48 48 27 35 39 27 37 32 Fibryga® (n=372) Cryoprecipitate (n=363) ⁴ N=735. There were 623 AEs in 248 patients in the fibryga® group and 673 AEs in 264 patients in the control group. A total of 27 thromboembolic events occurred in 26/372 (7.0%) patients in the fibryga® group and 39 occurred in 35/363 (9.6%) patients in the active control group. There were 35 deaths (9.4%) in the fibryga® group and 27 (7.4%) in the cryoprecipitate group (unadjusted hazard ratio, 1.28 [95% CI: 0.77–2.12]; p=0.35). The non-significant difference in mortality may have been related to a higher number of patients in a critical state in the fibryga® group versus active control group (16.9% vs 10.5%, respectively).AE, adverse event; SAE, serious adverse event.
Adapted from Callum et al, 2019. ²
AE 623 673 264 224 SAE Thromboembolic events Death Acute kidney injury Hepatobiliary disorders 0 800 100 200 300 400 500 600 700 48 48 27 35 39 27 37 32 Fibryga® (n=372) Cryoprecipitate (n=363) ⁴ N=735. There were 623 AEs in 248 patients in the fibryga® group and 673 AEs in 264 patients in the control group. A total of 27 thromboembolic events occurred in 26/372 (7.0%) patients in the fibryga® group and 39 occurred in 35/363 (9.6%) patients in the active control group. There were 35 deaths (9.4%) in the fibryga® group and 27 (7.4%) in the cryoprecipitate group (unadjusted hazard ratio, 1.28 [95% CI: 0.77–2.12]; p=0.35). The non-significant difference in mortality may have been related to a higher number of patients in a critical state in the fibryga® group versus active control group (16.9% vs 10.5%, respectively).AE, adverse event; SAE, serious adverse event.
Adapted from Callum et al, 2019. ²

UK-FIB-2500024 | May 2026

Abbreviations
ABPs, allogeneic blood products; AE, adverse event; AFD, acquired fibrinogen deficiency; CFD, congenital fibrinogen deficiency; CI, confidence interval; CRS, cytoreductive surgery; Cryo, cryoprecipitate; FAS, full analysis set; FXIII, IDMEAC, Independent Data Monitoring and Endpoint Adjudication Committee; IQR, interquartile range; LS, least squares; MCF, maximum clot firmness; MedDRA, Medical Dictionary for Regulatory Activities; N, number of patients; PK, pharmacokinetic; PMP, pseudomyxoma peritonei; PoC(T), point-of-care testing; PT, preferred term; PVT, portal vein thrombosis; RBC, red blood cell; ROTEM, rotational thromboelastometry; SAE, serious adverse event.

References

  1. Roy A, et al. Efficacy of fibrinogen concentrate in major abdominal surgery - A prospective, randomized, controlled study in cytoreductive surgery for pseudomyxoma peritonei. J Thromb Haemost. 2020;18:352–63.

  2. Callum J, et al. Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery: The FIBRES Randomized Clinical Trial. JAMA. 2019:322:1966–76.

  3. Fibryga® Summary of Product Characteristics (updated 13 Feb 2025). Available at: https://www.medicines.org.uk/emc/product/10315/smpc. Accessed May 2026.

  4. Abrahamyan L, et al. Cost-effectiveness of Fibrinogen Concentrate vs Cryoprecipitate for Treating Acquired Hypofibrinogenemia in Bleeding Adult Cardiac Surgical Patients. JAMA Surg. 2023;158(3):245–53.

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