EU approves bypassing agent Cevenfacta for haemophilia A or B

Cevenfacta is indicated in adults and adolescents (12 years of age and older) for the treatment of bleeding episodes and for the prevention of bleeding in those undergoing surgery or invasive procedures in the following patient groups: in patients with congenital haemophilia with high-responding inhibitors to coagulation factors VIII or IX (i.e. at least 5 Bethesda Units (BU)); in patients with congenital haemophilia with low titre inhibitors (BU <5), but expected to have a high anamnestic response to factor viii or factor ix administration or expected to be refractory to increased dosing of fviii or fix.

The approval of Cevenfacta was based on data from the phase III clinical trials, PERSEPT 1 and PERSEPT 3. The PERSEPT 1 Phase III, multicentre, randomised, open-label crossover study of two initial dose regimens (75 microg/kg and 225 microg/kg), evaluated 468 bleeding episodes across the full type of severity of bleeding episodes (mild, moderate, and severe), in 27 adolescent and adult haemophilia A and B patients with inhibitors (12-54 years of age). Both dosing regimens met the primary endpoint with 81% and 90% of bleeds controlled at 12 hours with the 75 microg/kg dose and the 225 microg/kg dose respectively. By 24 hours, haemostatic efficacy (secondary endpoint) was retained in 96.7% of bleeding episodes treated with the 75 microg/kg dose regimen and 99.5% of redundancy bleeding episodes treated with the 225 microg/kg dose, without requiring any alternative therapy. The median time to attain haemostatic efficacy was 5.98 hours for the 75 microg/kg dosing regimen and 3 hours for the 225 microg/kg dosing regimen. A median of 2 injections was needed to treat a bleeding episode with the 75 microg/kg and a median of only 1 injection of the 225 microg/kg dosing regimen was needed.

The PERSEPT 3 Phase III, multicentre, open-label, single-arm study evaluated the safety and efficacy of Cevenfacta in haemophilia A or B patients with inhibitors who were scheduled for an elective surgical or other invasive procedure. 12 patients were enrolled in the study, 6 with minor procedures and 6 with major procedures. For major surgical/invasive procedures, treatment was administered at an initial bolus dose of 200 microg/kg immediately before the start of the invasive procedure. For a minor elective surgical procedure, an initial bolus dose of 75 microg/kg was administered immediately before the start of the procedure. Overall, 81.8% of procedures were reported as successfully treated at 48 hours after the last administration of the product. No thromboembolic events were reported in these two clinical trials. No Serious Adverse Events (SAEs) were considered as related to the treatment.