High-Titer Inhibitors Reduced in PUPs with Severe Hemophilia A Treated with Fourth Generation Recombinant Factor VIII

A prospective, multinational, open-label Phase III study in previously untreated patients (PUPs) with severe hemophilia A found replacement therapy with simoctocog alfa (Nuwiq; Octapharma USA), a fourth-generation recombinant factor VIII (FVIII) product, was associated with an incidence of high-titer inhibitors similar to the rate seen in a landmark trial evaluating plasma-derived FVIII products, and significantly lower than the rate seen in PUPs treated with earlier-generation recombinant FVIII products in that same trial.

A total of 105 PUPs evaluable for inhibitor development received on-demand or prophylactic treatment with simoctocog alfa for a median of 101 exposure days (range one to 1,164), with 96 patients treated for greater than or equal to 100 exposure days. The cumulative high-titer inhibitor incidence was 17.6 percent (95 percent confidence interval [CI]: 10.0 percent to 25.5 percent), and 27.9 percent for cumulative inhibitors. This compares closely with the SIPPET study, which reported high-titer and any inhibitors in 18.6 percent and 26.8 percent of PUPs treated with plasma-derived FVIII products naturally containing von Willebrand factor. By contrast, SIPPET study patients treated with earliergeneration recombinant FVIII products had high-titer and cumulative inhibitor rates of 28.4 percent and 44.5 percent.

Simoctogoc alfa had a median spontaneous annualized bleeding rate of 0 during prophylaxis and was successful in the treatment of 92.9 percent of bleeding events and in 94.7 percent of surgical procedures. “These results complement results in previously treated patients (PTPs) and support the use of simoctocog alfa in the prevention and treatment of bleeding events in PUPs and PTPs,” the investigators concluded.