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
  • 95% successful efficacy outcome in treating bleeding events1
  • 100% successful efficacy outcome when considering only the first bleeding event1
  • 91% of bleeding events required a single infusion only1

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 in age from 12 to 53 years (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 13 patients with CFD (afibrinogenemia and hypofibrinogenemia), ranging in age from 13 to 53 years (2 adolescents, 11 adults)3
  • FORMA-04. Prospective, open-label, uncontrolled, phase 3 trial to assess clinical efficacy, safety
    and PK in a pediatric population (ongoing)

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 100% of bleeding episodes assessed by the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC)1

In the FORMA-02 interim analysis, there were 23 bleeding events defined as minor and included: mild joint bleeding, and superficial muscle, soft tissue, or oral bleeding.1,3 Approximately 2/3 of bleeds were spontaneous; the remaining were traumatic. Treatment of bleeding events was assessed using a 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, 95% were assessed as having a successful efficacy outcome (rating of good or excellent efficacy) by investigators and 100% by IDMEAC. (see Table)
  • When considering only the first bleeding event in each patient, all 10 bleeds (100%) were
    assessed as having a successful efficacy outcome1,3
  • For 91% of bleeds, just a single infusion of fibryga was needed to achieve control1,3
    • Median number of infusions required for bleeding events was 1
    • No bleeding event required more than 2 infusions (two bleeds required 2 infusions)
    • Median dose of fibryga per infusion for treatment of all bleeding events was 58 mg/kg
Hemostatic Efficacy Of fibryga For Treatment Of 23 Bleeding Events In 11 Patients
(Full Analysis Set-Bleeding Population)3
Efficacy Rating Investigator IDMEAC
4-Point Efficacy Scale N (%) N (%)
Excellent 19 (82.6) 23 (100)*
Good 3 (13.0)* 0
Moderate 0 0
None 0 0
Missing 1 (4.4)
2-Point Efficacy Scale† N (%) 90% CI N (%) 90% CI
Success 22 (95.7)§ 0.81–1.00 23 (100) 0.88–1.00
Failure 1 (4.3)§ 0

* For one patient experiencing one bleeding event, hemostatic efficacy was rated good by the investigator and excellent
by the IDMEAC despite underdosing with fibryga, with resulting maximum plasma fibrinogen levels of not more than 90% of the 100 mg/dL target. Analyses that added this bleeding event to the per-protocol data set showed no impact on overall hemostatic efficacy (21/22 [95.5%] bleeding events rated as treatment success by investigator and 22/22 [100%] bleeding events rated as treatment success by IDMEAC).
† Efficacy rating of excellent or good indicated success and efficacy rating of moderate or none indicated failure.
‡ 90% CI for the success rate was calculated according to Blyth-Still-Casella interval for the proportion of patients with successful hemostatic efficacy using a predefined threshold of 0.7.
§ For the purpose of success rate calculation, the missing assessment was considered a failure.

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For the first time in this rare disease setting, objective efficacy criteria were used as a robust method to determine hemostatic efficacy.3

References:
  1. Fibryga full Prescribing Information. Hoboken, NJ: Octapharma USA, Inc.; rev 2017.
  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. Efficacy and safety of a new human fibrinogen concentrate in patients with congenital fibrinogen deficiency: an interim analysis of a Phase III trial. Transfusion. 2018;58:413-422.