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

Abstract

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.

• Authors: P W Collins, D V K Quon, M Makris, P Chowdary, C L Kempton, S J Apte, M V Ramanan, C R M Hay, B Drobic, Y Hua, T J Babinchak, E D Gomperts
• Journal: Haemophilia : the official journal of the World Federation of Hemophilia (Haemophilia) Vol. 24 Issue 1 Pg. 104-112 (Jan 2018) ISSN: 1365-2516 [Electronic] England
• PMID: 28833808 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2017 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Chemical References

• Blood Coagulation Factor Inhibitors
• Recombinant Proteins
• Factor IX

Topics

• Adolescent
• Adult
• Area Under Curve
• Blood Coagulation Factor Inhibitors (blood)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Factor IX (adverse effects, pharmacokinetics, therapeutic use)
• Half-Life
• Headache (etiology)
• Hemophilia B (drug therapy, pathology)
• Hemorrhage (prevention & control)
• Humans
• Male
• ROC Curve
• Recombinant Proteins (pharmacokinetics, therapeutic use)
• Severity of Illness Index
• Treatment Outcome
• Young Adult