ReFacto AF

Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factor VIII; ATC code: B02BD02. ReFacto AF contains B-domain deleted recombinant coagulation factor VIII (moroctocog alfa). It is a glycoprotein with an approximate molecular mass of 170,000 Da consisting of 1438 amino acids. ReFacto AF has functional characteristics comparable to those of endogenous factor VIII. Factor VIII activity is greatly reduced in patients with haemophilia A, and, therefore, replacement therapy is necessary. When infused into a haemophiliac patient, factor VIII binds to the von Willebrand factor present in the patient's circulation. Activated factor VIII acts as a cofactor for activated factor IX, accelerating the conversion of factor X to activated factor X. Activated factor X converts prothrombin into thrombin. Thrombin then converts fibrinogen into fibrin, and a clot is formed. Haemophilia A is a sex-linked hereditary disorder of blood coagulation due to decreased levels of factor VIII:C and results in profuse bleeding into joints, muscles or internal organs, either spontaneously or as a result of accidental or surgical trauma. By replacement therapy, the plasma levels of factor VIII are increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies. Clinical efficacy The data in the table below relates to PUP and PTP data from ReFacto AF studies in patients <12 years. Consumption and efficacy results in paediatric population PTPs <6 years PTPs 6 to <12 years PUPs <6 years Dose by weight (IU/kg) per prophylaxis infusion a median (min, max) N=14 36 IU/kg (28, 51) N=13 32 IU/kg (21, 49) N=22 46 IU/kg (17,161) Total ABR all subjects b median (min, max) -- -- N=23 3.17 (0.0, 39.5) Total ABR for subjects who reported following an On Demand regimen at Baseline c median (min, max) N=5 41.47 (1.6, 50.6) N=9 25.22 (0.0, 46.6) -- Total ABR for subjects who reported following a Prophylaxis regimen at Baseline c median (min, max) N=13 1.99 (0.0, 11.2) N=9 5.55 (0.0, 13.0) -- Dose by weight (IU/kg) per bleeding episode for bleed treatment median (min, max) N=13 35 IU/kg (28, 86) N=14 33 IU/kg (17, 229) N=21 55 IU/kg (11, 221) % of bleeds treated successfully with ≤ 2 infusions 98.7% 98.8% 96.7% a The dose and frequency of ReFacto AF prescribed throughout the study were at the investigator's discretion as per local standard of care. b Subjects in the PUP study were not required to follow a regular continuous prophylaxis treatment; however, with the exception of one subject (with only on demand (OD) treatment) the majority of subjects took regular prophylaxis infusions. Several began with OD infusions but switched to prophylaxis treatment during their participation, and some had only sporadic prophylaxis infusions. c Subjects in the PTP study reported their FVIII treatment modality (prophylaxis or on demand) at baseline and were not required to maintain this modality as a condition of study participation. The dose and frequency of ReFacto AF prescribed throughout the study were at the investigator's discretion as per local standard of care. Abbreviations: ABR = annualised bleeding rate Of note, annualised bleeding rate (ABR) is not comparable between different factor concentrates and between different clinical studies. Immune Tolerance Induction Data on immune tolerance induction (ITI) have been collected in patients with haemophilia A who had developed inhibitors to factor VIII. As part of the pivotal trial with ReFacto in PUPs, ITI data from 25 patients were reviewed (15 with high titres, 10 with low titres). Of these 25 patients, 20 had a decrease in inhibitor titres to < 0.6 BU/mL, of whom initially 11 of 15 had high titres (≥ 5 BU/mL) and 9 of 10 had low titres. Out of 6 patients who developed low titre inhibitors but did not receive ITI, 5 had similar titre decreases. No long-term outcome is available.