Safety and Tolerability

Safety profile

  • In clinical trials, a similar safety profile was observed between fibryga and an active control comparator product1,2
  • No seroconversions for HIV, HAV, HBV, HCV, or
    Parvo B191-3
  • Most common adverse reactions (> 5% of subjects) were nausea, vomiting, pyrexia (fever) and thrombocytosis. Adverse events were generally mild, single events1-3

The most serious adverse reactions that may potentially be observed with fibryga are thromboembolic episodes and anaphylactic type reactions.3

Clinical trials experience1-3

In clinical trials, the most common adverse effects (>5% of subjects) were nausea, vomiting, pyrexia (fever) and thrombocytosis. Adverse effects were generally mild, single events.  Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of one drug cannot be directly compared to the rate in the clinical trials of another drug and may not reflect the rates observed in practice.1

In the FORMA-01 trial, a similar safety profile was observed between fibryga and the active control1

  • Adverse events (AEs) generally occurred as mostly mild, single events, with similar incidence
    and severity between treatment arms (see Table)
  • Separate occurrences of mild pyrexia and a mild allergic reaction occurred in two patients and were considered possibly related to fibryga
  • One severe AE (urinary tract infection) occurred 6 days after infusion and one patient experienced two serious AEs on the same day (abdominal pain and vaginal hemorrhage) 25 days after infusion, but these events were not considered treatment-related
  • There were no deaths or severe allergic reactions in the study, nor were there seroconversions (for HIV, HAV, HBV, HCV or parvovirus B19) related to either treatment
Summary of AEs in the fibryga FORMA-01 Trial1,2
N (%) of patients, Number of events
Fibryga Active Control
AEs 11 (50.0), 25 11 (50.0), 30
Mild
Moderate
Severe
8 (36.4), 15
4 (22.7), 9
1 (4.5), 1
9 (40.9), 26
3 (13.6), 4
0
Probably or possibly related AE 2 (9), 2 0
AE leading to withdrawal 0 0
SAE 1 (4.5), 2 0
Death 0 0

AE=adverse event; SAE=serious adverse event.

In the FORMA-02 trial2,3:

  • In total, 91 AEs in 19 patients (76.0%) were reported
  • Three AEs in three patients were considered possibly related to treatment: a moderate AE reported as exacerbation of a pre-existing condition of peripheral ischemia due to digital microthrombi, a mild skin reaction, and a mild AE reported as peripheral phlebitis of the upper limbs, all of which resolved
  • No deaths or severe allergic reactions were reported
  • No clinical evidence of neutralizing antifibrinogen antibodies
Summary of AEs (safety population)* in the fibryga FORMA-02 Trial2,3
Number of AEs
AE 91
Patients with AE, N (%) 19 (76.0)
Relatedness to treatment (probably or possibly related) 3
Non serious (mild)
Serious (moderate)
2
1§
AE leading to discontinuation 0
Death 0

*N=25 patients. Unless otherwise indicated, numbers are the number of AEs.
AEs include TEAEs, occurring between the start of the first fibrinogen concentrate infusion and the end of each 30-day observation and follow-up period, and non-TEAEs, AEs occurring outside of the follow-up period.
Mild skin reaction (itchiness and redness), peripheral phlebitis of the upper limbs.
§Ischemia due to digital microthrombi.
AE=adverse event; SAE=serious adverse event; TEAE=treatment-emergent AE.

In the FORMA-04 trial2,4:

  • In total, 10 AEs in 4 patients (28.6%) were reported
  • Two AEs in one patient were considered possibly related to treatment: portal vein thrombosis (PVT) and fever (pyrexia). The PVT was rated as an SAE and occurred after a splenectomy for spontaneous spleen rupture. The SAE was assessed as possibly related to fibryga while taking into consideration that PVT is a regular complication of splenectomy. The SAE led to the discontinuation of the patient from the study
  • No deaths or severe allergic reactions were reported
  • No clinical evidence of neutralizing antifibrinogen antibodies
Summary of AEs (safety population)* in the fibryga FORMA-04 Trial2,4
Number of AEs
AE 10
Patients with AE, N (%) 4 (28.6)
Mild
Moderate
Severe
7
2
1
Relatedness to treatment (probably or possibly related) 2
AE leading to discontinuation 1
SAE 1
Death 0

*N=14 patients. Unless otherwise indicated, numbers are the number of AEs
AEs include TEAEs, occurring between the start of the first fibrinogen concentrate infusion and the end of each 30-day observation and follow-up period, and non-TEAEs, AEs occurring outside of the follow-up period
AE leading to discontinuation was an SAE
AE=adverse event; SAE=serious adverse event; TEAE=treatment-emergent AE.

References:
  1. 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.
  2. Fibryga full Prescribing Information. Paramus, NJ: Octapharma; rev 2020.
  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