On-Demand Bleed Control

Overview

PUPs

PTPs

Header

On-demand treatment

	On-demand treatment in PTPs of 1,796 bleeding episodes were resolved with only 1 infusion²

	On-demand treatment in PUPs of 997 bleeding episodes were resolved with only 1 infusion³

FIX: factor IX; PTP: previously treated patient; PUP: previously untreated patient.

References:

Benefix Egyptian Drug Authority leaflet approval date: 14/11/2021. Revision Date: November 2020.

Roth DA, Kessler CM, Pasi KJ, et al. Human recombinant factor IX: safety and efficacy studies in hemophilia B patients previously treated with plasma-derived factor IX concentrates. Blood. 2001;98(13):3600-3606.

Shapiro AD, Di Paola J, Cohen A, et al. The safety and efficacy of recombinant human blood coagulation factor IX in previously untreated patients with severe or moderately severe hemophilia B. Blood. 2005;105(2):518-525.

Indicated for bleed control* in PUPs with heamophilia B²

	94.1% of responses were rated excellent or good in PUPs receiving an initial infusion of BeneFIX for on-demand treatment of hemophilia B² 2.9% of responses were rated moderate, 1% were rated as no response, 2% were not rated^†2 1505 infusions were given for on-demand treatment of 997 hemorrhages² All bleeding episodes were controlled²

	75% of bleeds were controlled after 1 infusion with BeneFIX (n = 748)² 14.9% were controlled after 2 infusions 5.4% were controlled after 3 infusions 2.4% were controlled after 4 infusions 2.2% were controlled after >4 infusions

BeneFIX Safety profile—supported by clinical trials in PUPs with hemophilia B²

2 out of 63 PUPs developed high-titer (>5 BU/dL) inhibitors in clinical trials.²

Both PUPs with high-titer inhibitors were withdrawn from the study²

The development of inhibitors occurs in 1% to 3% of patients with hemophilia B, but may be higher in individuals with severe disease. In the current study, the incidence of FIX inhibitor was 2 of 63 (3%) patients, which is consistent with previous reports of hemophilia B patients treated with pdFIX products or PTPs treated with rFIX²

56 patients received a total of 5032 infusions (mean ± SD: 89.86 ± 74.04) for a mean duration of exposure of 86.75 ± 71.73 days²

Study description:

This is a multicenter, international, open-label, single-cohort study. Patients received rFIX for on-demand treatment or routine prophylaxis continued on the study for at least 2 years, up to a maximum of 5 years or 100 exposure days, whichever occurred first. Patients who completed the core phase were allowed to enter the extension phase to receive rFIX for up to 1 additional year, at the discretion of the investigator and after prior written authorization from the sponsor.²

^*Study included 54 evaluable patients; median dose 62.7 IU/kg (range: 8.2-292 IU/kg).²

^aEfficacy was rated by the patient/guardian or investigator using a 4-point scale of “excellent,” “good,” “moderate,” or “no response,” consistent with the rating scale used in the rFIX hemophilia clinical study of PTPs.²

FIX: factor IX; IU: international unit; pdFIX: plasma-derived factor IX; PTP: previously treated patient; PUP: previously untreated patient; rFIX: recombinant factor IX; SD: Standard Deviation.

References:

Benefix Egyptian Drug Authority leaflet approval date: 14/11/2021. Revision Date: November 2020.

Indicated for bleed control in PTPs¹

	90.9% of responses were rated excellent or good in PTPs receiving an initial infusion of BeneFIX for on-demand treatment² 7.1% were rated as moderate, 0.7% were rated as no response, 1.3% were not rated^*2 2758 infusions were given for on-demand treatment of 1796 hemorrhages² All bleeding episodes were controlled²

	80.9% of bleeds were controlled after 1 infusion with BeneFIX² 11.6% were controlled after 2 infusions 3.6% were controlled after 3 infusions 1.8% were controlled after 4 infusions 2.1% were controlled after >4 infusions Study included 55 evaluable patients; median dose 42.8 IU/kg (range: 6.5-224.6 IU/kg).²

Safety in PTPs—low inhibitor formation with BeneFIX

1 out of 56 patients developed a low-titer transient inhibitor.²

Study description:

A 20-center international trial was conducted in PTPs with severe or moderate (<5 IU/dL factor IX activity) hemophilia B. Participants received rFIX for pharmacokinetic studies, treatment of or prophylaxis against hemorrhage, or surgical hemostasis, and were assessed at 3-month intervals for 2 years.²

*Bleed control rating scale: Efficacy was rated by the patient or investigator using a 4-point scale, based on a comparison with previously used pdFIX products for similar bleeds or procedures: excellent (as much and as rapid an improvement as the best pdFIX-related responses), good (as much and as rapid an improvement as most pdFIX-related responses), moderate (not as good as most pdFIX-related responses), or no response (no improvement).²

FIX: factor IX; IU: international unit; pdFIX: plasma-derived factor IX; PTP: previously treated patient; PUP: previously untreated patient; rFIX: recombinant factor IX.

References:

Benefix Egyptian Drug Authority leaflet approval date: 14/11/2021. Revision Date: November 2020.