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.

Real‐world assay variability between laboratories in monitoring of recombinant factor IX Fc fusion protein activity in plasma samples

“…Although only a limited number of samples were tested, these results suggest that the CS assay is a promising option for monitoring of rFIXFc activity in plasma samples. Previous studies have reported good correlation between assigned potency and CS activity for nonacog gamma (rFIX; Rixubis ® ) 20 and the PEGylated rFIX product N9‐GP in plasma 28 . By contrast, studies have shown a tendency for the CS assay to underestimate the activity of nonacog alfa (rFIX; BeneFIX ® ) by approximately 20% compared to the OSC assay 20,36 and to exhibit large discrepancies relative to OSC potency assignment for rIX‐FP 37 .…”

“…However, more recently, proficiency studies and manufacturer field studies have shown different levels of variability in measuring both rFIX and EHL rFIX products against the plasma FIX reference. 15,[20][21][22][23] One of the major reasons for interlaboratory variability in FIX measurements is the use of a large variety of aPTT reagents, 22 which can contain different types of contact activators (various forms of micronized silica, kaolin, ellagic acid or polyphenols) and different composition and sources of phospholipids (synthetic, plant-or animal-derived). Additional interlaboratory variability may be introduced when these reagents are mixed with FIX-depleted substrate plasma from different sources, subjected to further differences in assay protocols and analysed on different instruments.…”

“…Historically, clinical FIX assay discrepancies have not been a major concern in the testing of conventional rFIX products. However, more recently, proficiency studies and manufacturer field studies have shown different levels of variability in measuring both rFIX and EHL rFIX products against the plasma FIX reference 15,20‐23 …”

Global hemostatic assay of different target procoagulant activities of factor VIII and factor IX

“…Similarly, of the two rFIX concentrates available in Korea, only nonacog gamma was used in this study. Nonacog gamma is known to have less preactivated FIX, which is considered “impure content” influencing safety and efficacy, and is also known to have actual potency closer to its nominal potency [ 15 ].…”

“…Inclusion criteria were age of 15 years and older, and residual clotting factor activity of less than 3 IU/dL, based on a cohort study finding that the first joint bleeding that represents a more frequent bleeding phenotype occurs significantly earlier in patients who have less than 3 IU/dL residual clotting factor activity [ 14 ]. Although two kinds of recombinant FIX concentrates are available in Korea, only nonacog gamma was used in order to minimize any potential impact on the results of activated FIX content and potency variation [ 15 ]. Regarding hemophilia A, only users of full-length FVIII were included in the study.…”