For use in adults and children with hemophilia B for on demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes. Not for immune tolerance induction.
Help your patients protect more moments1
Rebinyn® prophylaxis helps stop bleeds before they start.1
Markus has hemophilia B and uses Rebinyn®.
Low annualized bleeding rate (ABR) with Rebinyn® prophylaxis
Data from paradigm 4 extension trial
spontaneous or traumatic
median ABR2
(n=52)
overall median ABR2,a
(n=52)
aABR of 1 was based on statistical calculation of median ABR for total bleeds in adult/adolescent patients.
Target joint resolution with Rebinyn® prophylaxis
Data from paradigm 4 extension trial
of target joints no longer classified as target joints3,b,c
median joint bleed ABR2
(n=52)
bPost hoc analysis of paradigm 2 and paradigm 4 data assessed the bleeding patterns in target joints in a population of patients with hemophilia B who received once-weekly prophylaxis with Rebinyn® 40 IU/kg.
cAs measured by International Society on Thrombosis and Haemostasis (1STH) target joint criteria. The most recent definition of a target joint from the ISTH is ≥3 spontaneous bleeds into the joint within a consecutive 6-month period. When there have been ≤2 bleeds into the joint within a consecutive 12-month period, the joint is no longer considered a target joint.3
In a retrospective, observational, real-world study of 42 patients, fewer bleeds were observed in patients who switched to Rebinyn®4,d
Data from the Canadian Bleeding Disorders Registry
Mean intrapatient ABR when switching from Alprolix® to Rebinyn® prophylaxis
Mean intrapatient ABR when switching from BeneFIX® to Rebinyn® prophylaxis
dBased on a retrospective, observational, real-world study of 42 patients with hemophilia B (5 patients were less than 18 years old) who switched from either BeneFIX® or Alprolix® prophylaxis to Rebinyn® prophylaxis using published Canadian Bleeding Disorders Registry (CBDR) data. Patients had to be on a previous therapy for at least 6 months and have at least 6 months of follow-up with Rebinyn®. CBDR formulary required a switch from Alprolix® to Rebinyn®, and patients had the option to switch from BeneFIX® to Rebinyn®. The study took place in part during the COVID-19 pandemic which limited attendance at hemophilia clinics for physical examinations. Total mean ABR is based on intrapatient bleeding, which is the bleeding rate in each patient before and after switching from BeneFIX® or Alprolix® prophylaxis to Rebinyn® prophylaxis.
Children ≤12 years (N=25) receiving once-weekly Rebinyn® achieved a median ABR of1,e:
Traumatic bleeds
Spontaneous bleeds
Joint bleeds
≤6 years
(n=12)
Traumatic bleeds
Spontaneous bleeds
Joint bleeds
7 to 12 years
(n=13)
Traumatic bleeds
Spontaneous bleeds
Joint bleeds
e25 previously treated children 0 to 12 years old received routine prophylactic administration of Rebinyn® 40 IU/kg once weekly for 52 weeks.1
Study designs
Young et al (2017)2
paradigm 4: phase 3 safety and efficacy extension trial
Patients: 71 male patients who had completed either the paradigm 2 or paradigm 3 clinical trials. Patients were aged 13 to 70 years with hemophilia B and had FIX activity ≤2 IU/dL, no history of inhibitors to FIX, and at least 150 exposure days to any FIX product.
Study design: Open-label, non-randomized, multicenter trial with four treatment arms: three once-weekly prophylactic groups (10 IU/kg, 40 IU/kg, and 80 IU/kg) and one on-demand group (40 IU/kg for mild and moderate bleeds, 80 IU/kg for severe bleeds). All patients were expected to have at least 50 additional exposure days to Rebinyn® during this extension trial. Treatment was mostly administered at home, with 2 clinic visits in the first 6 months and once every 6 months following. Prophylaxis patients received treatment during clinic visits, to allow pre-dose and post-dose blood samples and assessments.
Primary endpoint: Development of FIX inhibitors.
Secondary endpoints: Efficacy of Rebinyn® for bleed prophylaxis and when treating spontaneous or traumatic bleeding episodes. Assessment included number of bleeds and FIX activity.
Matino et al (2022)4
Switching to nonacog beta pegol in hemophilia B: Outcomes from a Canadian real-world, multicenter, retrospective study
Patients: Study included 42 Canadian patients with hemophilia B and treated with Rebinyn® prophylaxis for at least 6 months. Patients spanned all age groups and severity of hemophilia B. Secondary endpoint analysis included only those patients (n=42) with at least 6 months of data recorded with a previous product before switching to Rebinyn®.
Design: Retrospective analysis of data reported to the Canadian Bleeding Disorders Registry (CBDR) by 11 hemophilia treatment centers from April 2018 through March 2021. Two study groups, patients previously treated with Alprolix® and patients previously treated with BeneFIX®, were analyzed using negative binomial regression, to compare bleed rates, and a shared frailty gamma model, to compare recurrent bleeding incidents. CBDR formulary mandated a switch from Alprolix® to Rebinyn®, and patients had the option to switch from BeneFIX® to Rebinyn®.
Primary endpoint: Efficacy of Rebinyn® prophylaxis, including annualized bleeding rate, bleeding frequency in target joints, and target joint progression.
Secondary endpoint: Change in efficacy metrics and number of infusions required to treat a bleeding episode when patients switched to Rebinyn® from a previous FIX product.
Carcao et al (2016)5
paradigm 5: phase 3 clinical trial in children
Patients: 25 previously treated children with severe or moderately severe hemophilia B. Children were ≤12 years old, had an FIX activity level of ≤2%, had a history of ≥ 50 exposure days to other FIX products, and weighed ≥10 kg.
Study design: International, multicenter, open-label, non-controlled, single-arm trial designed following EMA guidelines. Patients were stratified into two age groups: 0–6 years and 7–12 years. The trial consisted of a main phase of 52 weeks, and an extension phase. All patients received a fixed dose of 40 IU/kg of Rebinyn® intravenously once weekly for prophylaxis. A pharmacokinetic (PK) assessment was conducted after the first dose of Rebinyn®, with the last PK sample collected 1 week after that dose and just prior to administration of the second dose. Breakthrough bleeds were treated with a single dose of 40 IU/kg of Rebinyn® (mild-to-moderate bleeds) or 80 IU/kg of Rebinyn® (severe bleeds).5
Primary endpoint: Immunogenicity of Rebinyn® as measured by the occurrence of FIX inhibitors (≥0.6 BU) over at least 50 exposure days.
Secondary endpoint: Efficacy of Rebinyn® in long-term prophylaxis as assessed by the estimated number of bleeds per year, success in treating breakthrough bleeds, and safety other than immunogenicity. FIX activity was also a secondary endpoint, measured after the first single-dose exposure and again at steady state.
Our safety record
Rebinyn® has an established clinical trial safety profile of over 13 years.6
Simple prophylaxis dosing
Convenient, once-weekly dosing for all patients.
Important Safety Information for Rebinyn®
Contraindications
- Rebinyn® is contraindicated in patients with a known hypersensitivity to Rebinyn® or its components, including hamster proteins.
Warnings and Precautions
- Hypersensitivity Reactions: Allergic-type hypersensitivity reactions, including anaphylaxis, have occurred with Rebinyn®. Signs may include angioedema, chest tightness, difficulty breathing, wheezing, urticaria, and itching. Discontinue Rebinyn® if allergic- or anaphylactic-type reactions occur and initiate appropriate treatment.
- Inhibitors: The formation of inhibitors (neutralizing antibodies) to Factor IX has occurred following Rebinyn®. If expected plasma factor IX activity levels are not attained, or if bleeding is not controlled as expected with the administered dose, perform an assay that measures Factor IX inhibitor concentration. Monitor all patients using clinical observations and laboratory tests for the development of inhibitors. Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used.
- Thrombotic Events: The use of Factor IX-containing products has been associated with thromboembolic complications. Monitor for thrombotic and consumptive coagulopathy when administering Rebinyn® to patients with liver disease, post-operatively, to newborn infants, or to patients at risk of thrombosis or disseminated intravascular coagulation (DIC).
- Nephrotic Syndrome: Nephrotic syndrome has been reported following immune tolerance induction therapy with Factor IX products in hemophilia B patients with Factor IX inhibitors, often with a history of allergic reactions to Factor IX. The safety and efficacy of using Rebinyn® for immune tolerance induction have not been established.
Adverse Reactions
- The most common adverse reactions reported in previously treated patients in clinical trials (≥1%) were itching and injection site reactions. The most common adverse reactions (≥1%) in previously untreated patients reported in clinical trials were rash, FIX inhibitors, hypersensitivity, itching, injection site reaction, and anaphylactic reaction.
- Animals administered Rebinyn® showed accumulation of PEG in the choroid plexus, pituitary, circumventricular organs, and cranial motor neurons. The potential clinical implications of these animal findings are unknown. Consider whether the patient is vulnerable to cognitive impairment, such as infants and children who have developing brains, and patients who are cognitively impaired.
Please click here for Rebinyn® Prescribing Information.
Indications and Usage
Rebinyn®, Coagulation Factor IX (Recombinant), GlycoPEGylated, is a recombinant DNA derived coagulation Factor IX concentrate indicated for use in adults and children with hemophilia B (congenital Factor IX deficiency) for on demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes.
Limitations of Use: Rebinyn® is not indicated for immune tolerance induction in patients with hemophilia B.
Important Safety Information for Rebinyn®
Contraindications
- Rebinyn® is contraindicated in patients with a known hypersensitivity to Rebinyn® or its components, including hamster proteins.
Warnings and Precautions
- Hypersensitivity Reactions: Allergic-type hypersensitivity reactions, including anaphylaxis, have occurred with Rebinyn®. Signs may include angioedema, chest tightness, difficulty breathing, wheezing, urticaria, and itching. Discontinue Rebinyn® if allergic- or anaphylactic-type reactions occur and initiate appropriate treatment.
- Inhibitors: The formation of inhibitors (neutralizing antibodies) to Factor IX has occurred following Rebinyn®. If expected plasma factor IX activity levels are not attained, or if bleeding is not controlled as expected with the administered dose, perform an assay that measures Factor IX inhibitor concentration. Monitor all patients using clinical observations and laboratory tests for the development of inhibitors. Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used.
- Thrombotic Events: The use of Factor IX-containing products has been associated with thromboembolic complications. Monitor for thrombotic and consumptive coagulopathy when administering Rebinyn® to patients with liver disease, post-operatively, to newborn infants, or to patients at risk of thrombosis or disseminated intravascular coagulation (DIC).
- Nephrotic Syndrome: Nephrotic syndrome has been reported following immune tolerance induction therapy with Factor IX products in hemophilia B patients with Factor IX inhibitors, often with a history of allergic reactions to Factor IX. The safety and efficacy of using Rebinyn® for immune tolerance induction have not been established.
Adverse Reactions
- The most common adverse reactions reported in previously treated patients in clinical trials (≥1%) were itching and injection site reactions. The most common adverse reactions (≥1%) in previously untreated patients reported in clinical trials were rash, FIX inhibitors, hypersensitivity, itching, injection site reaction, and anaphylactic reaction.
- Animals administered Rebinyn® showed accumulation of PEG in the choroid plexus, pituitary, circumventricular organs, and cranial motor neurons. The potential clinical implications of these animal findings are unknown. Consider whether the patient is vulnerable to cognitive impairment, such as infants and children who have developing brains, and patients who are cognitively impaired.
Please click here for Rebinyn® Prescribing Information.
Indications and Usage
Rebinyn®, Coagulation Factor IX (Recombinant), GlycoPEGylated, is a recombinant DNA derived coagulation Factor IX concentrate indicated for use in adults and children with hemophilia B (congenital Factor IX deficiency) for on demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes.
Limitations of Use: Rebinyn® is not indicated for immune tolerance induction in patients with hemophilia B.
References:
- Rebinyn [package insert]. Plainsboro, NJ: Novo Nordisk Inc.
- Young G, Collins PW, Colberg T, et al. Nonacog beta pegol (N9-GP) in haemophilia B: a multinational phase III safety and efficacy extension trial (paradigm 4). Thromb Res. 2016;141:69-76.
- Negrier C, Young G, Abdul-Karim F, et al. Recombinant long-acting glycoPEGylated factor IX (nonacog beta pegol) in haemophilia B: assessment of target joints in multinational phase 3 clinical trials. Haemophilia. 2016;22(4):507-13.
- Matino D, Iorio A, Keepanasseril A, et al. Switching to nonacog beta pegol in hemophilia B: Outcomes from a Canadian real-world, multicenter, retrospective study. Res Pract Thromb Haemost. 2022;6(3):e12661.
- Carcao M, Zak M, Abdul Karim F, et al. Nonacog beta pegol in previously treated children with hemophilia B: results from an international open-label phase 3 trial. J Thromb Haemost. 2016;14(8):1521-1529.
- Novo Nordisk A/S. Safety of 40K PEGylated recombinant Factor IX in non-bleeding patients with haemophilia B. ClinicalTrials.gov identifier: NCT00956345. Updated January 20, 2017. Accessed June 3, 2022. https://clinicaltrials.gov/ct2/show/NCT00956345