Obizur

Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factors, ATC code: B02BD14 Mechanism of action Obizur is a recombinant, B‑domain deleted, porcine sequence factor VIII (susoctocog alfa). It is a glycoprotein. Immediately after release in the patient's circulation, factor VIII binds to von Willebrand factor (vWF). The factor VIII/von Willebrand factor complex consists of two molecules (factor VIII and von Willebrand factor) with different physiological functions. Activated factor VIII acts as a co‑factor for activated factor IX, accelerating the conversion of factor X to activated factor X, which ultimately converts prothrombin into thrombin. Thrombin then converts fibrinogen into fibrin and a clot can be formed. Acquired haemophilia is a rare bleeding disorder in which patients with normal factor VIII genes develop inhibitory autoantibodies directed against factor VIII. These autoantibodies neutralise circulating human factor VIII thus creating a deficiency of available factor VIII. Circulating antibodies (inhibitors) targeted against human factor VIII have minimal or no cross reactivity against OBIZUR. OBIZUR temporarily replaces the inhibited endogenous factor VIII that is needed for effective haemostasis. Clinical efficacy and safety The safety and efficacy of OBIZUR for the treatment of serious bleeding episodes in patients with acquired haemophilia with autoimmune inhibitory antibodies to human factor VIII was investigated in a prospective, non‑randomised, open‑label study of 28 patients (18 Caucasian, 6 Black, and 4 Asian). The study included patients presenting with life and / or limb threatening bleeding requiring hospitalisation. All initial bleeding episodes had a positive response to treatment at 24 hours after initial dosing as assessed by the primary investigator. A positive response was one where bleeding had stopped or was reduced, with clinical improvement or with factor VIII activity above a pre‑specified target. A positive response was observed in 95% (19/20) of patients evaluated at 8 hours and 100% (18/18) at 16 hours. In addition to response to treatment, the overall treatment success was determined by the investigator based on his/her ability to discontinue or reduce the dose and/or dosing frequency of OBIZUR. A total of 24/28 (86%) had successful control (resolution) of the initial bleeding episode. Of those patients treated with OBIZUR as first‑line therapy, defined as no immediate previous use of anti‑haemorrhagic agents prior to the first OBIZUR treatment, 16/17 (94%) had eventual treatment success reported. Eleven patients were reported to have received anti‑haemorrhagic agents (e.g. rFVIIa, activated prothrombin‑complex concentrate, tranexamic acid) prior to first treatment with OBIZUR. Of these 11patients, eight had eventual successful treatment (73%). The median dose per injection to successfully treat the primary bleed was 133 U/kg and the median total dose was 1523 U/kg for a median of 6 days. The median number of daily infusions per patient was 1.76 (range: 0.2 to 5.6). In the initial 24 hour period, the median total dose of 493 U/kg were utilised in the clinical study with a median of 3 infusions. When treatment was required beyond 24 hours, a median total dose of 1050 U/kg were utilized with a median of 10.5 infusions (median dose 100 U/kg) to control a bleeding episode. In the clinical study of OBIZUR for acquired haemophilia, 29 adult patients were evaluable for safety. Nineteen subjects did not have a detectable anti-porcine factor VIII inhibitor titer at baseline (< 0.6 BU/mL). Of the 19 subjects, twelve had no detectable anti-porcine factor VIII titer post-treatment, five had an increase in titer (≥ 0.6 BU/ml), and two subjects had no post-treatment samples analysed and seven subjects developed anamnestic reactions with a rise ≥ 10 BU in human factor VIII and/or recombinant factor VIII porcine sequence inhibitors. In the clinical study of OBIZUR in patients with congenital haemophilia A with FVIII inhibitors (CHAWI) undergoing surgery, out of 8 adult patients evaluable for safety analysis a total of 5 subjects experienced anamnestic reactions. Paediatric population The licensing authority has waived the obligation to submit the results of studies with OBIZUR in all subsets of the paediatric population in treatment of acquired haemophilia (see section 4.2 for information on paediatric use). This medicinal product has been authorised under 'exceptional circumstances'. This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product. The licensing authority will review any new information which may become available every year and this SmPC will be updated as necessary.