Table 2.
Assays performed at 15% and 100% AT levels and impact of fitusiran.
| Assays performed | Impact of fitusiran | FVIII | FIX | ||||||
|---|---|---|---|---|---|---|---|---|---|
| PT assay using Dade Innovin on the BCS XP System, s | Target AT (%)/fitusiran (ng/mL) concentration | 15/0 | 15/1000 | 100/0 | 100/1000 | 15/0 | 15/1000 | 100/0 | 100/1000 |
| Mean (SD) | 12.4 (0.1) | 12.4 (0.1) | 12.4 (0.1) | 12.4 (0.1) | 11.7 (0.0) | 11.7 (0.1) | 10.8 (0.0) | 10.8 (0.1) | |
| % change | 0.0 | −0.2 | 0.3 | 0.3 | |||||
| aPTT assay using Dade Actin FSL on the BCS XP System, s | Target AT (%)/fitusiran (ng/mL) concentration | 15/0 | 15/1000 | 100/0 | 100/1000 | 15/0 | 15/1000 | 100/0 | 100/1000 |
| Mean (SD) | 61.1 (0.9) | 60.6 (0.4) | 56.0 (0.3) | 56.1 (0.3) | 62.9 (1.0) | 63.9 (0.2) | 62.3 (0.2) | 63.2 (1.3) | |
| % change | −0.9 | 0.2 | 1.6 | 1.4 | |||||
| One-stage clot assay using Dade Actin FSL on the BCS XP System, % | Target AT (%)/fitusiran (ng/mL) concentration | 15/0 | 15/1000 | 100/0 | 100/1000 | 15/0 | 15/1000 | 100/0 | 100/1000 |
| Mean (SD) | 0.3 (0.0) | 0.3 (0.0) | 0.3 (0.0) | 0.3 (0.0) | NI | NI | NI | NI | |
| % change | −10.0 | 0.0 | NI | NI | |||||
| Chromogenic assays | |||||||||
| FVIII chromogenic assay using Coatest SP4 (Chromogenix) on the BCS XP System, IU/mL | Target AT (%)/fitusiran (ng/mL) concentration | 15/0 | 15/1000 | 100/0 | 100/1000 | – | – | – | – |
| Mean (SD) | NI | NI | NI | NI | – | – | – | – | |
| % change | NI | NI | – | – | – | – | |||
| FIX chromogenic assay using Hyphen BioMed BIOPHEN FIX Kit on the BCS XP System, % | Target AT (%) concentration | – | – | – | – | 15/0 | 15/1000 | 100/15 | 100/1000 |
| Mean (SD) | – | – | – | – | NI | NI | NI | NI | |
| % change | – | – | – | – | NI | NI | |||
| Nijmegen inhibitor assays | |||||||||
| FVIII one-stage clot Nijmegen Bethesda assay using Dade Actin FSL on the BCS XP System, BU/mL | Target AT (%)/fitusiran (ng/mL) concentration | 15/0 | 15/1000 | 100/0 | 100/1000 | 15/0 | 15/1000 | 100/0 | 100/1000 |
| Mean (SD) | 0.2 (0.1) | 0.1 (0.1) | 0.1 (0.1) | 0.1 (0.1) | 0.4 (0.1) | 0.3 (0.0) | 0.3 (0.1) | 0.3 (0.1) | |
| % change | −50.0a | 0.0 | −18.9 | −10.0 | |||||
| FIX one-stage clot Nijmegen Bethesda assay using Dade Actin FSL on the BCS XP System, BU/mL | Target AT (%)/fitusiran (ng/mL) concentration | 15/0 | 15/1000 | 100/0 | 100/1000 | 15/0 | 15/1000 | 100/0 | 100/1000 |
| Mean (SD) | – | – | – | – | 0.4 (0.1) | 0.3 (0.0) | 0.3 (0.1) | 0.3 (0.1) | |
| % change | – | – | −18.9 | −10.0 | |||||
| FVIII chromogenic Nijmegen Bethesda assay using Siemens FVIII Chromogenic Assay Kit on the BCS XP System, BU/mL | Target AT (%) concentration | 15/0 | 15/1000 | 100/0 | 100/1000 | – | – | – | – |
| Mean (SD) | 0.0 (0.0) | 0.0 (0.0) | 0.0 (0.1) | 0.0 (0.1) | – | – | – | – | |
| % change | 0.0 | 0.0 | – | – | – | – | |||
The impact of fitusiran was defined as “none” if there was ±15% variability between the samples with and without fitusiran. For the Nijmegen inhibitor assays, the acceptable variability was ±20%. All assays were performed in triplicate. The “–“ symbol indicates unavailable data, as the assay is specific to either FVIII or FIX.
aPTT, activated partial thromboplastin time; AT, antithrombin; BU, Bethesda Units; FIX/FVIII, factor IX/VIII; NI, no interference; PT, prothrombin time; SD, standard deviation.
a
As all results were <0.6 BU/mL, it was deemed that there was no impact by fitusiran.