Presentation Highlights

During Monday’s Oral Session of Hemorrhagic Disorders: Pediatric Aspects, Guy Young, M.D. presented interim results from the pivotal HAVEN 2 clinical trial. These results were consistent with the positive results of the HAVEN 1 trial, also presented at the 2017 ISTH Congress today.

  • Emicizumab is a novel, humanized, monoclonal antibody that promotes coagulation by bridging factor IXa (FIXA) and FX, replacing the function of missing FVIII in the setting of severe Hemophilia A.
  • Emicizumab prophylaxis was safe and reduced bleeds in pediatric patients with Hemophilia A and Inhibitors (PwHAwI):
    • Clinically meaningful reductions in annualized bleeding rates (ABR) compared with historical ABR were noted.
    • The pharmacokinetic profile of emicizumab in children was similar to the profile reported in adult PwHAwI.
    • Emacizumab was well tolerated, with no severe adverse events related to drug administration reported in the study patients.

HAVEN 2 demonstrates that emicizumab may reduce the treatment and disease burden for pediatric PwHAwI.

HAVEN 2 is a single-arm, multicenter, open-label, phase 3 study evaluating efficacy, safety, and pharmacokinetics of once-weekly subcutaneous emicizumab prophylaxis in pediatric persons with hemophilia A with inhibitors (PwHAwl). The goal of this study was to assess the efficacy, safety, and pharmacokinetics of this regimen in children and adolescents. Patients who were younger than 12 years of age (or 12-17 years if the patient weighed <40 kg), and had previously been treated with FVIII bypassing agents were enrolled to receive emicizumab prophylaxis for at least 52 weeks.

Interim analysis included 20 PwHAwl aged 3 to 12 years (median: 8.5 years); 19 patients less than 12 years of age were included in the efficacy analyses. The median observation time was 12.1 weeks (range: 7-14 weeks). In total, 18 (94.7%) subjects had no bleeds requiring treatment, and 12 (63.2%) had no bleeds of any severity while on study. Overall, 14 bleeds were reported in 7 subjects, but none of these occurred in a joint or muscle.

A substantial reduction in ABR while on study vs. ABR from a non-interventional study (NIS) was observed in the 8 subjects included in the intra-person comparison; all 8 patients had 100% reduction in treated bleeds, 5/8 had 100% reduction in number of all bleeds, and all subjects had more than 76% reduction in all bleeds. Emicizumab was well tolerated, with the most common adverse events (AEs) being mild injection-site reactions (15%) and nasopharyngitis (15%). No thromboembolic or thrombotic microangiopathy events were reported, and no anti-drug antibodies were detected. Mean trough emicizumab concentrations did not differ from those previously reported in adults. The data also indicate that the same dose of emicizumab can be used for children as for adults and adolescents, based on blood levels of emicizumab in children compared with those reported in adults and adolescents.

Emicizumab prophylaxis was safe and prevented or reduced bleeds in pediatric PwHAwI, showing clinically meaningful reductions in ABR compared with historical ABR. These interim data show the potential for emicizumab to reduce the treatment and disease burden for pediatric PwHAwI.

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