Efficacy

Gain control when you need it most

  • Fibryga supplements missing coagulation factor or increases low plasma fibrinogen levels in patients with CFD1
  • Effective in restoring clot strength (maximum clot firmness [MCF])1
  • 99% successful efficacy outcome in treating bleeding events in adolescents and adults1,3
  • 93% of bleeding events required a single infusion only1,3
  • 100% successful efficacy outcome in treating bleeding events in pediatric patients1,4

The fibryga clinical trial program in CFD comprises the FORMA-01, FORMA-02 and FORMA-04 studies

Forma Timeline Graphic

  • FORMA-01. Prospective, controlled, randomized, crossover trial to assess pharmacology of fibryga vs active control in 22 CFD patients ranging from 12 to 53 years of age (6 adolescents, 16 adults).1,2 Pharmacokinetic results are discussed here.
  • FORMA-02. Prospective, open-label, uncontrolled, multicenter trial for on-demand treatment of acute bleeding in 24 patients with CFD (afibrinogenemia and hypofibrinogenemia), ranging from 12 to 54 years of age (6 adolescents, 18 adults)3
  • FORMA-04. Prospective, open-label, uncontrolled, phase 3 trial to assess clinical efficacy, safety and PK in a pediatric population in 8 children ranging from 1 to 10 years of age.4

Significant increase in clot strength (measured by MCF)1-2

  • In the FORMA-01 trial, patients with CFD each received fibryga in a single IV 70 mg/kg dose.
    MCF was determined before (baseline) and 1 hour after infusion
  • For every patient, MCF values were significantly higher after administration of fibryga vs baseline (see Table); mean change from pre-infusion to 1 hour post-infusion was 9.7 mm in the primary analysis
  • After the cross-over trial, similar increases in MCF were observed for fibryga and the active control comparator product (Figure); the mean difference between treatments (0.32 mm [95% CI, -1.70, 1.07]) was not significant
FORMA-01: MCF (mm) Pre-and Post-Infusion in the Intention-to-Treat Population (N=22)1
Time Point Mean ± SD Median (Range)
Pre-Infusion 0 ± 0 0 (0-0)
1 Hour Post-Infusion 9.7± 3.0 10.0 (4.0-16.0)
Mean Change (Primary Analysis)* 9.7 ± 3.0 10.0 (4.0-16.0)

* P<0.0001 (95% CI 8.37, 10.99)
MCF = maximum clot firmness; SD = standard deviation

Change in MCF from baseline to 1 hour after fibryga or active control (N=22)2

GS1228-Figue-8_v3

Box plot shows the median (horizontal line), mean (diamond), upper and lower quartiles (box ends) and minimum and maximum (whiskers) within 1.5 × interquartile range.

Source: Ross C, Rangarajan S, Karimi, M, et al.  Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency. J Thromb Haemost. 2018;16:253-261.

Fibryga achieved good or excellent efficacy in 98.9% of bleeding episodes in the adolescent and adult study and 100% in the pediatric study, as assessed by the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC)1

In the FORMA-02 study with adolescents and adults, there were 86 bleeding events defined as minor, including mild joint bleeding, and superficial muscle, soft tissue, or oral bleeding.1,3 One bleed was defined as major, including spontaneous intracranial hemorrhage. Approximately 75% of bleeds were spontaneous; the remaining were traumatic. Treatment of bleeding events was assessed using an objective 4-point hemostatic efficacy scale based on criteria such as bleeding cessation, changes in hemoglobin, and use of any other hemostatic means.1,3

  • Of the evaluable bleeding events, 98.9% were assessed as having a successful efficacy outcome (a rating of good or excellent efficacy) by IDMEAC
  • For 93% of bleeds, just a single infusion of fibryga was needed to achieve control1,3
  • The median dose of fibryga per infusion for treatment of all bleeding events was 57 mg/kg

Efficacy of fibrinogen concentrate for on-demand treatment of bleeding episodes in adults and adolescents in FORMA-02 (N=89 BEs in 24 patients)3

*Two BEs with missing investigator assessments were adjudicated/scored by the IDMEAC.
The success rate is a rating of excellent/good, with 90% confidence intervals calculated according to the Blyth–Still–Casella interval for the proportion of patients with successful hemostatic efficacy.
BE = bleeding episode; IDMEAC = Independent Data Monitoring and Endpoint Adjudication Committee; N = number of BEs

In the FORMA-04 study with children, there were 10 bleeding events, 8 minor and 2 major.1,4 Half of the bleeds were spontaneous; the other half were traumatic. Treatment of bleeding events was assessed using an objective 4-point hemostatic efficacy scale based on criteria such as bleeding cessation, changes in hemoglobin, and use of any other hemostatic means.1,4

  • Of the evaluable bleeding events, 100% were assessed as having a successful efficacy outcome (a rating of good or excellent efficacy) by IDMEAC
  • For 100% of minor bleeds, just a single infusion of fibryga was needed to achieve control1,4
  • The median dose of fibryga per infusion for treatment of all bleeding events was 70 mg/kg
  • Efficacy of fibrinogen concentrate for on-demand treatment of bleeding episodes in children in FORMA-04 (N=10 BEs in 8 patients)4

    *For one patient, the hemostatic efficacy assessment was missing. As per the statistical analysis plan, the rating by the investigator was designated as “None”.
    The success rate was a rating of excellent/good, with 95% confidence intervals calculated by the Clopper Pearson Method.
    BE = bleeding episode; IDMEAC = Independent Data Monitoring and Endpoint Adjudication Committee; N = number of BEs

AF9A6817-2D20-4D8C-B33B-095687B49132 Created with sketchtool.

For the first time in this rare disease setting, robust analysis methodology using objective efficacy criteria was implemented, demonstrating the hemostatic efficacy of fibryga.3

References:
  1. Fibryga full Prescribing Information. Paramus, NJ: Octapharma; rev 2020.
  2. Ross C, Rangarajan S, Karimi M, et al. Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency. J Thromb Haemost. 2018;16:253-261.
  3. Lissitchkov T, Madan B, Djambas Khayat C, et al. Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients. J Thromb Haemost. 2020;18(4):815-824
  4. Khayat C, Lohade S, et al. Efficacy and safety of fibrinogen concentrate for on-demand treatment of bleeding and surgical prophylaxis in paediatric patients with congenital fibrinogen deficiency. Haemophilia. 2021;27(2):283-292.