Low Rate of Inhibitor Development in Previously Untreated Hemophilia A Patients Managed with Simoctocog Alfa (Nuwiq)

Final results from Octapharma’s Phase III open label, uncontrolled NuProtect study demonstrated a low risk of inhibitor development in previously untreated patients (PUPs) with severe hemophilia A started on prophylaxis or on-demand treatment with simoctocog alfa (Nuwiq). Simoctocog alfa is a fourth-generation recombinant factor VIII (FVIII) produced in a human cell line. Initiated in March 2013, this study recruited patients of any age and ethnicity at 38 sites in 17 countries, and followed them for 100 exposure days or five years, whichever occurred first.

All patients were true PUPs with no prior exposure to FVIII concentrates or blood components. Inhibitor titers were measured with the Nijmegen-modified Bethesda assay. The cut-off for inhibitor positivity was 0.6 Bethesda units (BU), with ≥0.6 to <5 BU defining low-titer inhibitors, and ≥5 BU defining high-titer inhibitors.

Of 105 evaluable PUPs who received simoctocog alfa for the prevention and treatment of bleeding, 28 (26.7 percent) developed inhibitors, including 17 (16.2 percent) who developed high-titer inhibitors and 11 (10.5 percent) who developed low- titer inhibitors. Twenty-seven of 90 PUPs with known null FVIII mutations developed inhibitors, of which 17 (18.9 percent) were high-titer inhibitors. None of 12 PUPs with non-null FVIII mutations developed inhibitors.

Based on a review of recent published clinical trial findings, the investigators concluded PUPs treated with simoctocog alfa had a lower high-titer inhibitor rate than PUPs initially treated with hamster-cell-derived recombinant FVIII products.