Activity measurements of dalcinonacog alfa

INTRODUCTION: Many recombinant and modified FIX products have been, and continue to be, developed with the aim of improving treatment for patients with haemophilia B. One such new product is dalcinonacog alfa, a recombinant FIX with modifications to provide improved features such as subcutaneous administration. AIM: In view of previously observed assay discrepancies with modified FIX therapeutics, the aim of this study was to assess potential discrepancies in potency measurement of dalcinonacog alfa between and within different assay methods. METHODS: Potency of dalcinonacog alfa was measured against the 5th International Standard (IS) for FIX Concentrate and the 4th IS for FIX Plasma by One‐Stage Clotting Assay, using 9 different APTT reagents and 2 commercially available FIX chromogenic kits. Plasma‐derived concentrate and recombinant FIX samples were also included for comparison in every assay. RESULTS: Substantial discrepancies were observed when assaying dalcinonacog alfa using the one‐stage clotting assay against both standards. No statistically valid results were obtained when testing dalcinonacog alfa using either chromogenic kit. Increasing the incubation time with the activation reagent in both chromogenic kits resulted in valid assays and increased the potency to become more in line with potencies by one‐stage clotting assays. Increasing the incubation time in the chromogenic kits had no effect on the potencies of the plasma‐derived or recombinant samples. However, incubation time influenced in the one‐stage clotting assay using Dapttin. CONCLUSIONS: Within and between assay method discrepancy was found when assaying dalcinonacog alfa. Methods for potency labelling and clinical monitoring should be given careful consideration.