Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors

Amy D. Shapiro*, Pantep Angchaisuksiri, Jan Astermark, Gary Benson, Giancarlo Castaman, Hermann Eichler, Victor Jiménez-Yuste, Kaan Kavakli, Tadashi Matsushita, Lone Hvitfeldt Poulsen, Allison P. Wheeler, Guy Young, Silva Zupančić-Šalek, Johannes Oldenburg, Pratima Chowdary

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Despite current therapies, there remains an unmet need for treatment for patients with hemophilia. The main parts of two phase 2 trials established clinical proof-of-concept for once-daily, subcutaneous concizumab prophylaxis in patients with hemophilia A/B with inhibitors (HAwI/HBwI; explorer4) and severe hemophilia A without inhibitors (HA; explorer5). Here, we present results from extension parts of these trials, included to evaluate longer term safety and efficacy. Both trials included main (≥24 weeks) and extension (52-102 weeks) parts, with patients receiving concizumab 0.15 mg/kg with potential dose escalation to concizumab 0.20 or 0.25 mg/kg if they experienced ≥3 treated spontaneous bleeding episodes within 12 weeks. Endpoints included annualized bleeding rate (ABR), adverse events (AEs), and occurrence of antidrug antibodies. Thromboembolic events were AEs of special interest. Thirty-six patients with HA, 15 with HAwI, and 10 with HBwI were exposed to concizumab. Estimated ABRs during the main + extension parts at last dose level were 4.8 (95% confidence interval [CI], 3.2-7.2) and 6.4 (95% CI, 4.1-9.9) in explorer4 and explorer5, respectively (spontaneous ABRs were 1.8 [95% CI, 1.2-2.6] and 2.1 [95% CI, 1.3-3.3]). Most AEs were mild, with no deaths, events leading to withdrawal, or thromboembolic events. Anti-drug antibodies developed in 25% of patients and were low titer and transient, with no observed clinical effect in most cases. Results of the main + extension parts of these trials were consistent with results of the main parts. Ongoing phase 3 trials will further evaluate concizumab as a once-daily, subcutaneous treatment across hemophilia subtypes. These trials were registered at www.clinicaltrials.gov as #NCT03196284 and #NCT03196297.

Original languageEnglish
JournalBlood Advances
Pages (from-to)3422-3432
Number of pages11
Publication statusPublished - Jun 2022


  • Antibodies, Monoclonal, Humanized/adverse effects
  • Clinical Trials as Topic
  • Hemophilia A/drug therapy
  • Hemophilia B/drug therapy
  • Hemorrhage/chemically induced
  • Humans


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