Efficacy and safety

Reliable efficacy when you and your patients need it most1,2

Prophylaxis

Prophylactic treatment in PTPs
reduction in ABR vs on-demand In PTPs. ReFacto® prophylaxis is more effective at preventing bleeds than on-demand treatment, with an 85% reduction of bleeds per year (median ABR: 3.4; n=154) achieved with prophylactic treatment3

 

On-demand treatment

On-demand treatment in PTPs
of 10,882 bleeding episodes were treated effectively with only 1 infusion (n=113)1,2
On-demand treatment in PUPs
of 2,715 bleeding episodes were treated effectively with only 1 infusion (n=101)1,2
Surgery
of infusions administered were rated as excellent or good by the surgeon and treating physician (38 patients; 48 surgical procedures; 496 infusions during or after surgery)1,*

 

ReFacto AF® is manufactured using the same cell line as ReFacto4 and is pharmacokinetics-equivalent to ReFacto®5, so it is expected to behave in the same way.

*Excellent rating: achievement of comparable haemostasis to that expected after similar surgery in a non-haemophilic patient. Good rating: prolonged time to haemostasis with somewhat increased bleeding compared with that expected after similar surgery in a non-haemophilic patient.1

 

Safety

A favourable safety profile5

The most common adverse reactions reported in pooled clinical trials with 715 subjects (591 PTPs, 124 PUPs)5:

  • Factor VIII inhibitors in PUPs, headache, cough, arthralgia and pyrexia – very common (≥10%)
  • Factor VIII inhibitors in PTPs - uncommon (>0.1 to <1%). Decreased appetite, dizziness, haemorrhage, haematoma, diarrhoea, vomiting, abdominal pain, nausea, urticaria, rash, pruritus, myalgia, chills, catheter-site-related reaction, antibody test positive and anti-factor VIII antibody test positive – common (≥1% to <10%)

 

Inhibitor formation

PTPs1,3,6–8

  Inhibitor incidence De novo inhibitors
ReFacto® 1/113 (0.9%)1,6 0/113 (0%)2,6
ReFacto AF® 3/110 (2.7%)7 1/110 (0.9%)7

 

Switching from recombinant or plasma-derived factor to ReFacto AF® did not significantly increase the risk of inhibitor formation.3,8

PUPs6

  Inhibitor incidence High-titre (≥5 BU/ml) inhibitors
ReFacto® 32/101 (32%)6 16/32 (50%)6

 

 

References

1. Lusher JM et al. The safety and efficacy of B-domain deleted recombinant factor VIII concentrate in patients with severe haemophilia. Haemophilia 2003;9:38–49.

2. Lusher JM and Roth DA. The safety and efficacy of B-domain deleted recombinant factor VIII concentrates in patients with severe haemophilia A: an update. Haemophilia 2005;11:292–293.

3. Parra Lopez R et al. Prospective surveillance study of haemophilia A patients switching from moroctocog alfa or other factor VIII products to moroctocog alfa albumin-free cell culture (AF-CC) in usual care settings. Thromb Haemost. 2015;114(4):676–684.

4. Kelley B et al. An improved manufacturing process for Xyntha/ReFacto AF. Haemophilia 2010;16(5):717–725.

5. ReFacto AF® (moroctocog alfa) Summary of Product Characteristics. October 2019.

6. Courter SG and Bedrosian CL. Clinical evaluation of B-domain deleted recombinant factor VIII in previously treated patients. Semin Hematol 2001;38(2):44–51.

7. Recht M et al. Clinical evaluation of moroctocog alfa (AF-CC), a new generation of B-domain deleted recombinant factor VIII (BDDrFVIII) for treatment of haemophilia A: demonstration of safety, efficacy, and pharmacokinetic equivalence to full-length recombinant factor VIII. Haemophilia 2009;15(4):869–880.

8. Hay CR et al. The incidence of factor VIII inhibitors in severe haemophilia A following a major switch from full-length to B-domain-deleted factor VIII: a prospective cohort comparison. Haemophilia 2015;21(2):219–222.

 

ABR = annualised bleeding rate; BU = Bethesda units; PTP = previously treated patient; PUP = previously untreated patient.

 

PP-REF-GBR-0176. October 2019.