Concizumab, an anti\u2013tissue 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.<\/p>\n
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.<\/p>\n
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\u2019s own bleeding history during prior on-demand treatment, going back at least 26 weeks.<\/p>\n
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.<\/p>\n
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.<\/p>\n
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.<\/p>\n
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\u2013neutralizing antibodies to concizumab, although these did not appear to affect drug levels, pharmacodynamics, efficacy, or safety by the cutoff.<\/p>\n
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?<\/p>\n
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.<\/p>\n","protected":false},"excerpt":{"rendered":"Concizumab, an anti\u2013tissue factor pathway inhibitor (TFPI) antibody, lowered the annualized bleeding rate (ABR) by 82% in children…\n","protected":false},"author":2,"featured_media":539680,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5],"tags":[114,85,46],"class_list":["post-539679","post","type-post","status-publish","format-standard","has-post-thumbnail","category-business","tag-business","tag-il","tag-israel"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/539679","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/comments?post=539679"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/539679\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media\/539680"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media?parent=539679"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/categories?post=539679"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/tags?post=539679"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}