Today Dr. Jan Astermark presented phase II results on concizumab in Hemophilia A and Hemophilia A/B patients with inhibitors.  Concizumab is a high affinity, humanized, monoclonal antibody which inhibits Tissue Factor Pathway Inhibitor (TFPI).  It is believed that anti-TFPI could restore hemostasis in a manner that does not require the activity of factors VIII or IX and thus provide a valuable treatment approach for haemophilia patients. 

The aims of this phase II program were to evaluate the safety and efficacy of once-daily, subcutaneous concizumab prophylaxis in patients with hemophilia A/B with inhibitors (HAwI/HBwI) (Explorer 4) and severe hemophilia A without inhibitors (HA) (Explorer 5), and to establish the optimal dose regimen for the phase 3 trials.  Thirty-six HA, nine HAwI and eight HBwI patients were exposed to concizumab in the main phases (24 weeks) of the studies. Patients received initially 0.15 mg/kg concizumab with potential dose escalation to 0.20 and 0.25 mg/kg.

Clinical proof-of-concept for once-daily subcutaneous concizumab prophylaxis was established and all completing patients chose to continue into the extension phase.  Thrombin generation potential was restored to within normal range and the annual bleeding rate was significantly reduced in patients with inhibitors on prophylaxis compared to on demand. Dr. Astermark concluded that concizumab was safe and well tolerated; there were no thromboembolic events, no AE-related withdrawals, no safety concerns related to the concomitant use of FVIII products or rFVIIa. Anti-concizumab antibodies were reported in 6/53 patients, but with no observed clinical effect.

Dr. Astermark concluded that the “Phase 2 trial results confirmed the proof of concept, with no safety signals, and has guided selection of the phase 3 dosing regimen. Further development of concizumab as a prophylactic treatment for all hemophilia patients is supported.”  As part of this important work, breakthrough therapy designation has been granted by the FDA based on the HBwI data.

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