Immunogenicity, safety, and efficacy of rurioctocog alfa pegol in previously untreated patients with severe hemophilia A: interim results from a phase 3, prospective, multicenter, open-label study.

AIM: To determine the immunogenicity, safety, and efficacy of rurioctocog alfa pegol in previously untreated patients (PUPs) with severe hemophilia A (HA). METHODS: This prospective, phase 3 study (NCT02615691) was conducted in PUPs, or patients with ≤2 exposure days (EDs) prior to screening, aged <6 years with severe HA. The primary endpoint was incidence of factor VIII (FVIII) inhibitor development. This protocol-specified interim analysis was conducted after 50 patients had completed ≥50 EDs without developing FVIII inhibitors or had developed a confirmed inhibitor at any time. RESULTS: Of the enrolled patients, 59/80 (73.8%) received ≥1 dose of rurioctocog alfa pegol; 54 received prophylaxis, and 35 on-demand treatment. Incidence of inhibitor development was 0.19 (10/52). Total annualized bleeding rate (95% CIs) was 3.2 (2.0-5.0) for patients receiving prophylaxis and 3.2 (1.6-6.3) for on-demand treatment. Hemostatic efficacy of most bleedings was rated as 'excellent' or 'good' after 24 hours (122/131 [93.1%]) and at resolution (161/170 [94.7%]). Five patients received ≥1 dose of rurioctocog alfa pegol for immune tolerance induction (ITI) and 1 patient was defined as having ITI success. Thirteen patients experienced 14 treatment-related adverse events, including 10 cases of FVIII inhibitor development. CONCLUSION: This is the first prospective study of rurioctocog alfa pegol for the treatment of PUPs with severe HA. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02615691).

Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura.

Safety, tolerability, and pharmacokinetics of recombinant ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; BAX 930; SHP655) were investigated in 15 patients diagnosed with severe congenital ADAMTS-13 deficiency (plasma ADAMTS-13 activity <6%) in a prospective phase 1, first-in-human, multicenter dose escalation study. BAX 930 was well tolerated, no serious adverse events occurred, and no anti-ADAMTS-13 antibodies were observed. After single-dose administration of BAX 930 at 5, 20, or 40 U/kg body weight to adolescents and adults, there was approximate dose proportionality with respect to maximum plasma concentration (Cmax [U/mL]) and area under the concentration-time curve (AUC [h∙U/mL]). Dose-related increases of individual ADAMTS-13:Ag and activity were observed and reached a maximum within 1 hour. With escalating BAX 930 doses administered, a dose-dependent persistence of ADAMTS-13-mediated von Willebrand factor (VWF) cleavage products and reduced VWF multimeric size were observed. This study demonstrated that pharmacokinetic parameters of BAX 930 were comparable to those estimated in previous plasma infusion studies and provided evidence of pharmacodynamic activity. This study was registered at www.clinicaltrials.gov as #NCT02216084.