Nonacog gamma, a novel recombinant factor IX with low factor IXa content for treatment and prophylaxis of bleeding episodes

Abstract

Nonacog gamma is a new recombinant factor IX to treat factor IX deficiency. It is indicated for control of bleeding episodes, perioperative management and routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia B. Nonacog gamma was first approved in the USA in June 2013 under the trade name RIXUBIS followed by market approvals in Australia and the EU in 2014, and marketing authorization decision is pending in Japan. Nonacog gamma is derived from a recombinant Chinese hamster ovary cell line using a state of the art biotechnological manufacturing process. Recombinant factor IX is produced by Baxter’s protein-free fermentation technology, which was first developed for ADVATE. The product is purified and formulated in the absence of any human or animal-derived protein. Nonacog gamma was characterized both in comprehensive in vitro and in vivo non-clinical studies as well as in an extensive clinical trial program.

Keywords:

• activated factor IXa
• hemophilia B
• nonacog gamma
• prophylaxis
• recombinant factor IX
• RIXUBIS

Acknowledgements

The authors thank S Mandl and K Benamara for editorial assistance with this manuscript.

Financial & competing interest disclosure

All authors are employees of Baxter Healthcare or its subsidiaries, the sponsor of the non-clinical and clinical studies for nonacog gamma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Nonacog gamma is a recombinant factor IX product derived from cell culture of a Chinese hamster cell line expressing human factor IX. Nonacog gamma is based on the protein-free technology, avoiding the use of human or animal-derived proteins throughout manufacturing and in the final formulation and is based on the technology that has been developed for the recombinant human factor VIII product ADVATE.

• Potency of nonacog gamma is measured with the one-stage clotting assay. Assay variability is comparable to that of nonacog alfa, another recombinant factor IX product.

• Structural and functional characterization and non-clinical studies established comparability of nonacog gamma with nonacog alfa with one difference: nonacog gamma was found to have substantially lower levels of activated factor IX than nonacog alfa.

• Nonacog gamma has undergone a comprehensive clinical development program consisting of a pivotal Phase I/III, a pediatric Phase II/III trial, a continuation Phase III study and a surgery Phase III study.

• Studies with nonacog gamma in patients with severe and moderate hemophilia B demonstrated pharmacokinetic properties comparable to that of nonacog alfa.

• Prophylaxis with nonacog gamma was shown to be efficacious and resulted in a reduction of frequency of bleeding episodes.

• In a surgery study, nonacog gamma provided safe and efficacious hemostasis in hemophilia B patients undergoing surgeries.

• In all clinical studies, nonacog gamma demonstrated safety in patients with hemophilia B with no incidence of development of inhibitory antibodies to factor IX or host cell proteins. No thrombotic event occurred in any subject involved in the clinical trial program. Also no severe allergic reactions were reported.

Notes

¹Continuation study (ongoing): The safety, immunogenicity and hemostatic efficacy of nonacog alfa are currently under evaluation in a continuation study. The primary end point is AEs possibly or probably related to nonacog gamma. Secondary end points are presented in relation to safety, immunogenicity, PK, hemostatic efficacy and health-related quality of life parameters.