Once-weekly prophylaxis regimen of nonacog alfa in patients with hemophilia B: An analysis of timing of bleeding event onset

Abstract

In a pivotal, multicenter, open-label study, 25 patients aged 12-54 years with moderately severe/severe hemophilia B received on-demand nonacog alfa (6 months; dose at investigator's discretion) followed by once-weekly prophylaxis with nonacog alfa 100 IU/kg (12 months). During prophylaxis, patients had a median spontaneous annualized bleeding rate (sABR) of 1.0 and significant reductions in ABR (P < 0.0001). This post hoc analysis examined the time of onset of spontaneous bleeding events (sBEs) and spontaneous target joint bleeding events (sTJBEs). The postdosing day (D) of onset of sBEs observed during prophylaxis and steady-state FIX activity data (FIX:C) between 144 and 196 h postdose were collected at weeks 26 and 78. Twelve patients (48%) had no sBEs; the remaining 13 (52%) had the following onset of sBEs: less than 1 D (0%), 1 to less than 2D (5%), 2 to less than 3 D (22%), 3 to less than 4 D (9%), 4 to less than 5D (22%), 5 to less than 6D (23%), 6 to less than 7D (11%), and at least 7D (8%). Reductions in sBEs and sTJBEs during on-demand versus prophylaxis treatment were experienced by all 13 patients. Target joint sABR during prophylaxis was 0 for 5/13 patients. ABR reduction ranged from 66.1% (27.2→9.2) to 97.8% (46.2→1.0); sTJBE reductions ranged from 6.2% (2.1→2.0) to 100% (from 40.1, 19.1, 3.9, 9.0, 6.1 - 0). During prophylaxis, 47% (8/17) of trough FIX activity samples were more than 2%. In sBE patients, ABR and number of TJBEs were reduced with once-weekly nonacog alfa. When sBEs occurred, they followed no apparent pattern for day of occurrence. Clinicaltrials.gov identifier: NCT01335061.