Concizumab, an anti–tissue factor pathway inhibitor (TFPI) antibody, lowered the annualized bleeding rate (ABR) by 82% in children younger than 12 years with hemophilia A or B and inhibitors in phase 3 of the Explorer10 trial, as reported by the investigators at the International Society on Thrombosis and Haemostasis (ISTH) 2026 Congress in Paris, France.
Concizumab is given once daily by subcutaneous injection. Regulators in the US, Europe, and other countries have already cleared it for treatment of hemophilia A or B with or without inhibitors in patients aged 12 years and older. Explorer10 (aims to expand its use to younger children with hemophilia A or B and inhibitors.
The study was nonrandomized and carried out at multiple centers. Participants were boys younger than 12 years who had hemophilia A or B with or without inhibitors. One group of boys had never received concizumab (arm 1); the other group had received it through compassionate use (arm 2). Patients not previously treated with concizumab began treatment with a 1.0 mg/kg loading dose and received 0.20 mg/kg daily, beginning on day 2, with titration to 0.15 or 0.25 mg/kg allowed at weeks 5 to 8 based on plasma concentration. Efficacy was measured against each patient’s own bleeding history during prior on-demand treatment, going back at least 26 weeks.
Data from 24 boys made up the primary analysis. During treatment with concizumab, their estimated mean ABR was 2.08% (95% CI, 1.27%-3.41%), compared with 11.51% (95% CI,7.75%-17.09%) during earlier on-demand treatment. That put the ABR ratio at 0.18 (95% CI, 0.11-0.29; P<0.001). Median ABR moved from 6.0 to 0.9. Thirteen of the 24 patients, or 54.2%, had no treated bleeds through the first 32 weeks, across 36.8 participant-years of exposure.
When spontaneous bleeds were considered separately from traumatic bleeds, the drop was steeper: mean ABR of 0.98 versus 6.82, a decrease of 86% (ratio, 0.14; P<0.001). Twenty of the 24 boys, 83.3%, had no spontaneous bleeding episodes.
Plasma concizumab levels remained steady over the study period. The free TFPI level fell and remained low. The geometric mean thrombin peak climbed into the normal adult range.
Safety was assessed in all 42 boys in both arms. Serious adverse events were reported for 12 of them (28.6%). There were no deaths, no withdrawals due to adverse events, and no thromboembolic events, which the protocol tracked as events of special interest. Injection-site reactions occurred in six boys (14.3%). Nine (21.4%) developed in vitro–neutralizing antibodies to concizumab, although these did not appear to affect drug levels, pharmacodynamics, efficacy, or safety by the cutoff.
For clinicians, two questions stand out. Will the bleed reductions and the clean thromboembolic record hold up as follow-up runs well past 32 weeks and more children are enrolled? Should the 21.4% rate of neutralizing antibodies, so far without consequence, prompt closer immunogenicity monitoring over the long term?
The investigators concluded that in children with hemophilia A or B and inhibitors, concizumab prophylaxis prevented bleeds better than on-demand treatment, with a safety profile consistent with earlier findings.