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.
aBased upon a 2.34% increase in factor levels per IU/kg infused in adults.
Long-lasting bleed control with Rebinyn® Prophylaxis1,2
Rebinyn® once-weekly helps adults and adolescents maintain FIX levels in the non-hemophilia range for most of the week2,b
Adult and adolescent patients achieved FIX levels in the non-hemophilia range for approximately 80% of the week (n=9)2,b
Adult and adolescent patients achieved FIX levels in the non-hemophilia range (n=9)2,b
bData represent mean steady-state pharmacokinetic profiles from previously treated adolescent/adult patients with moderate to severe hemophilia B (n=9) taking Rebinyn® 40 IU/kg once weekly. Factor IX levels were within the non-hemophilia range (greater than 40%) for 5.4 days (approximately 80% of the week).2
High incremental recovery and sustained high factor levels for bleed protection1,c,d
See study designs
paradigm 2 and paradigm 4
Adults
Adolescents
High incremental recovery1,c
Adults
(n=6)
Adolescents
(n=3)
High FIX peak levels1,d
Adults
(n=20)
Adolescents
(n=9)
Long-lasting half-life1,e
Adults
(n=6)
Adolescents
(n=3)
High FIX trough levels1,d
Adults
(n=20)
Adolescents
(n=9)
cIncremental recovery: defined as the activity of nonacog beta pegol recorded 30 min after end of injection divided by dose (IU/mL)/(IU/kg).2
dBased on the mean steady-state post-dose peak levels and pre-dose trough levels 168 hours after administered Rebinyn® 40 IU/kg once weekly in previously treated patients (20 adult and 9 adolescent patients).1
eBased on analysis using a 1-stage assay in 6 patients age ≥18 and 3 patients age 13-17 following once-weekly (40 IU/kg) dosing. Following single-dose administration (40 IU/kg) in the same patient population, the half-life was 83 hours (adults) and 89 hours (adolescents).1
Help pediatric patients sustain powerful bleed control
Rebinyn® prophylaxis maintains high factor levels throughout the dosing interval for pediatric patients.1
Children aged 0-6
(n=12)
Children aged 7-12
(n=13)
Mean FIX peak levels at steady statef
Children aged 0-6
(n=12)
Children aged 7-12
(n=13)
Half-lifeg
Children aged 0-6
(n=12)
Children aged 7-12
(n=13)
Mean FIX trough level at day 7f
Children ages 0-6
(n=12)
Children ages 7-12
(n=13)
fMean steady-state pre-dose trough levels and post-dose peak levels across the clinical trials for all previously treated children aged ≤6 (n=12) and 7 to 12 years (n=13) receiving Rebinyn® 40 IU/kg once weekly.1
gBased on single-dose pharmacokinetic parameters of Rebinyn® in children aged ≤6 (n=12) and 7 to 12 years (n=13).1
Rebinyn® provides high incremental recovery that boosts FIX levels into a range that, when combined with the extended half-life of Rebinyn®, allows for prolonged periods in the non-hemophilia range.1,2,b-e
Do you see teens like Karla?
Karla is 17 and lives with mild hemophilia B. Learn more about what patients like her are looking for in a factor IX treatment.
For illustrative purposes.
Study designs
Collins et al (2014)3
paradigm 2: pivotal phase 3 trial in adults and adolescents
Patients: 74 male patients aged 13 to 70 years with hemophilia B. Patients had FIX activity ≤2 IU/dL, no history of inhibitors to FIX, and at least 150 exposure days to any FIX product.
Study design: Patients were selected for prophylaxis or on-demand treatment at screening. On-demand patients participated in the trial for 28 weeks and received a single dose of 40 IU/kg for bleeding episodes (80 IU/kg for severe bleeding episodes). Prophylaxis patients participated for 52 weeks. Prophylaxis patients were randomly divided into groups of 10 IU/kg once weekly and 40 IU/kg once weekly. Patients were blinded to the prophylaxis dose. The investigator was blinded but could become unblinded if it became necessary to measure a patient’s FIX activity. A pharmacokinetic assessment of the two prophylactic doses was conducted using a subset of these patients. Pharmacokinetic assessments were based on a 1-stage clotting assay and performed at trial initiation (single dose assessments) and after 12 to 44 weeks of prophylaxis (steady state assessments) with both trial doses. The assessments included 7 sampling points up to 168 hours post injection.
Primary endpoint: Safety of Rebinyn®, measured by factors including development of FIX inhibitors (per Nijmegan modified Bethesda assay), adverse events, noninhibitory binding antibodies against Rebinyn®, and antibodies against host cell proteins.
Secondary endpoints: Efficacy of Rebinyn® for bleed prophylaxis and when treating spontaneous or traumatic bleeding episodes. Assessment included number of doses, amount of product used, duration of bleed, and annual bleed rate.
Young et al (2017)4
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.
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.
Compare PK of FIX products using modeling data
Explore modeling data comparing Rebinyn® with SHL and EHL FIX products.
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.
- Tiede A, Abdul-Karim F, Carcao M, et al. Pharmacokinetics of a novel extended half-life glycoPEGylated factor IX, nonacog beta pegol (N9-GP) in previously treated patients with haemophilia B: results from two phase 3 clinical trials. Haemophilia. 2017;23(4):547-555.
- Collins PW, Young G, Knobe K, et al; paradigm 2 Investigators. Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial. Blood. 2014;124(26):3880-3886.
- 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.
- 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.