Estimation of Nuwiq^®(simoctocog alfa) activity using one‐stage and chromogenic assays—Results from an international comparative field study

Abstract

Background Accurate determination of coagulation factor VIII activity (FVIII:C) is essential for effective and safe FVIII replacement therapy. FVIII:C can be measured by one‐stage and chromogenic substrate assays (OSAs and CSAs, respectively); however, there is significant interlaboratory and interassay variability. Aims This international comparative field study characterized the behaviour of OSAs and CSAs used in routine laboratory practice to measure the activity of Nuwiq® (human‐cl rhFVIII, simoctocog alfa), a fourth‐generation recombinant human FVIII produced in a human cell line. Methods FVIII‐deficient plasma was spiked with Nuwiq® or Advate® at 1, 5, 30 and 100 international units (IU)/dL. Participating laboratories analysed the samples using their routine procedures and equipment. Accuracy, inter‐ and intralaboratory variation, CSA:OSA ratio and the impact of different OSA and CSA reagents were assessed. Results Forty‐nine laboratories from 9 countries provided results. Mean absolute FVIII:C was comparable for both products at all concentrations with both OSA and CSA, with interproduct ratios (Nuwiq®:Advate®) of 1.02‐1.13. Mean recoveries ranged from 97% to 191% for Nuwiq®, and from 93% to 172% for Advate®, with higher recoveries at lower concentrations. Subgroup analyses by OSA and CSA reagents showed minor variations depending on reagents, but no marked differences between the two products. CSA:OSA ratios based on overall means ranged from 0.99 to 1.17 for Nuwiq® and from 1.01 to 1.17 for Advate®. Conclusions Both OSAs and CSAs are suitable for the measurement of FVIII:C of Nuwiq® in routine laboratory practice, without the need for a product‐specific reference standard.

Evaluation of anti‐factor VIII antibodies in haemophilia A subjects switching products following a provincial tender

“…Even if slight differences were noted for mean FVIII recovery measured by one-stage clotting assay at visit 1 between children and adults (all products-combined; p = 0.0003; 1.95, 1.76, 1.8 respectively at visit 1, 2, 3 for children; 2.61, 2.40, 2.40 respectively at visit 1, 2, 3 for adults) as well as between Nuwiq® and Zonovate® (p = 0.0042; 2.09, 1.74, 1.9 respectively at visit 1, 2, 3 for Nuwiq®; 2.65, 2.38, 2.38 respectively at visit 1, 2, 3 for Zonovate®), all values were still comparable to previous reports, [4][5][6][7] considering that 49.6% of our subjects were obese (20.1%) or overweight (29.5%) 8,9 and that 73% of the children in our cohort were switched to Nuwiq®. 7 As previously observed in clinical trials for Nuwiq® and Zonovate® in previously treated PWHA, [10][11][12][13] no inhibitors were detected upon study entry by Nijmegen-modified Bethesda (NBA) assay or enzyme-linked immunosorbent assay (ELISA; used as a complementary approach to detect both neutralizing and non-neutralizing antibodies) even in the 3 subjects with less than 50 ED.…”

Monitoring standard and extended half‐life products in hemophilia: Assay discrepancies for factor VIII and IX in pre‐ and postinfusion samples

“…Generalized product‐by‐product–based guidance about systematic under‐ or overestimation of activity for many reagent combinations is needed. Field studies for many new products, and in Europe UK NEQAS and ECAT quality control programs have also been performed and provided valuable information for the coagulation laboratories 13‐16 . For both Nuwiq and Elocta, field studies indicate that both OSA and CSA can be used for monitoring.…”

Laboratory measurement of factor replacement therapies in the treatment of congenital haemophilia: A United Kingdom Haemophilia Centre Doctors’ Organisation guideline

“…The authors concluded that Nuwiq can be measured with both one-stage and chromogenic assays without the need for a product specific standard. 29 Recommendations for monitoring Nuwiq 1. We recommend that one-stage and chromogenic FVIII assays calibrated with plasma standards can be used for monitoring…”

“…There were only minor differences between results obtained with different reagents. The authors concluded that Nuwiq can be measured with both one‐stage and chromogenic assays without the need for a product specific standard …”