Pharmacokinetics, safety and efficacy of a recombinant factor IX product, trenonacog alfa in previously treated haemophilia B patients.

INTRODUCTION: Trenonacog alfa (IB1001) is a recombinant factor IX (rFIX) manufactured in Chinese hamster ovary (CHO) cells. IB1001 was evaluated in a multicentre clinical trial with haemophilia B patients.

AIM: The aim was to establish IB1001 pharmacokinetic non-inferiority to comparator rFIX, safety and efficacy in previously treated patients (PTPs) with haemophilia B.

METHODS: Subjects were severe or moderately severe haemophilia B adult and adolescent PTPs with no history of FIX inhibitors.

RESULTS: IB1001 PK non-inferiority to comparator rFIX was demonstrated through ratio of AUC0-∞ in 32 subjects. IB1001 was well tolerated in all 76 treated subjects; the most common adverse drug reaction was headache (2.6% of subjects) and there were no reports of FIX inhibitors. Transient non-inhibitory binding FIX antibodies and anti-CHO cell protein antibodies developed in 21% and 29% of subjects respectively; no safety concerns were associated with development of these antibodies. Prophylaxis (mean duration ± SD: 17.9 ± 9.6 months, mean dose: 55.5 ± 12.9 IU/kg, median 1.0 infusion per week) was effective in preventing bleeds (median annual bleed rate: 1.52, interquartile range: 0.0-3.46). One or two IB1001 infusions resolved 84% of the bleeds, while for 84% of treatments haemostatic efficacy of IB1001 was rated excellent or good. IB1001 haemostatic efficacy for all 19 major surgeries was rated adequate or better than adequate.

CONCLUSIONS: IB1001 is safe and efficacious for treatment of bleeds, routine prophylaxis and perioperative management in haemophilia B patients.