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.
PK=pharmacokinetic.
aPhase 1 trial comparing PK of Rebinyn® with SHL FIX products (Negrier, et al). Based upon a phase 1 study of patients administered 1 of 3 doses of Rebinyn® (25, 50, or 100 IU/kg) compared with 1 dose of their prior SHL rFIX (n=7) or pdFIX (n=8) at the same dose using a 1-stage assay. Estimated mean PK parameters were adjusted to a dose of 50 IU/kg. Differences were similar in comparison of Rebinyn® to pdFIX (half-life 93 vs 18 hours, 5.2x; P<0.001; AUC 70 vs 9 U x h/ml, 8x, P<0.001) and in comparison of Rebinyn® to rFIX (half-life 93 vs 19 hours, P<0.001; AUC 72 vs 7 U x h/ml, P<0.001). The clinical relevance of these PK differences is unknown.1
bPhase 1 trial comparing PK of Rebinyn® with Alprolix® (Ettingshausen, et al). Based upon a phase 1 study of 15 patients administered a single dose of Rebinyn® 50 IU/kg compared with a single dose of Alprolix® 5O IU/kg using both 1-stage and chromogenic assays. The standard Alprolix® dose of 50 IU/kg was administered for both products to allow for comparison of dose-dependent parameters; dose normalized to 5O IU/kg to reflect minor differences in dose administered. Geometric mean half-life was also prolonged (Rebinyn®: 103.2 hours, Alprolix®: 84.9 hours). All comparisons were significant (P<0.0001) for all assays. The clinical relevance of these PK differences is unknown.3
Compare Rebinyn® with BeneFIX®
In a phase 1 study, Rebinyn® allowed patients to achieve and maintain a higher factor level compared with BeneFIX®.1,a The clinical relevance of these PK differences is unknown.
Rebinyn® achieved and maintained higher factor activity for longer1,a
The half-life of Rebinyn® was 93 hours vs 19 hours for BeneFIX®.1,a
Compare Rebinyn® with Alprolix®
In the paradigm 7 study, Rebinyn® allowed patients to achieve and maintain a higher factor level compared with Alprolix®.3,b The clinical relevance of these PK differences is unknown.
Rebinyn® achieved and maintained higher factor activity for longer3,b
The half-life of Rebinyn® was 103 hours vs 85 hours for Alprolix®.3,b
Rebinyn® can help raise Factor IX levels so your patients can be ready for the unexpected.4
Would switching to Rebinyn® prophylaxis help a patient like Colin?
Colin is 46 and lives with severe hemophilia B. He experiences joint pain that sometimes limits his activities, and he is looking for a treatment that keeps him in the non-hemophilia range for as long as possible.
Find out more about what patients like Colin look for when considering a therapy switch.
For illustrative purposes.
Study designs
Negrier et al (2011)1
paradigm 1: Rebinyn® first human dose trial, including pharmacokinetic analysis
Patients: 15 previously treated male hemophilia B patients with FIX activity ≤2% and at least 150 days of exposure to a FIX product before enrollment.
Study design: Open-label dose escalation trial. Patients were administered one of three doses of Rebinyn® (25, 50, or 100 IU/kg) no less than 7 days after receiving the same dose of their prior SHL rFIX (N=7) or pdFIX (N=8). Blood samples for pharmacokinetic analysis were drawn before dose and again at 30 mins for dosing with any product, as well as at 7 intervals after dosing with a patient’s prior product (ending at 48 hours postdose) and 13 intervals after dosing with Rebinyn® (ending at 4 weeks after dosing). Inhibitors were measured using a Nijmegan modified Bethesda assay, and FIX activity was measured using a modified aPTT assay.
Primary endpoint: Safety of Rebinyn® as evaluated by adverse events, antibody formation including inhibitors against FIX and Rebinyn®, physical examination, vital signs, electrocardiogram, injection site reactions, urinalysis, and clinical laboratory asessments.
Secondary endpoint: Pharmacokinetic assessment of Rebinyn® and comparison to other FIX products, based on FIX coagulation activity measurements.
Ettinghausen et al (2019)3
paradigm 7: open-label crossover trial comparing Rebinyn® and recombinant Factor IX-Fc fusion protein (rFIXFc)
Patients: 15 previously treated male patients aged 18 to 70 years with hemophilia B. Patients had FIX activity ≤2 IU/dL and at least 150 exposure days to any FIX product.
Study design: Patients were randomly assigned a single 50 IU/kg dose of either Rebinyn® or rFIXFc, followed by a 50 IU/kg dose of the other product at least 21 days later. Pharmacokinetic (PK) assessment was performed on blood samples drawn over 10 days postdose for each product, using both 1-stage and chromogenic assays.
Primary endpoint: Area under the FIX activity-time curve for each product.
Secondary endpoints: PK endpoints including maximum FIX activity dose-normalized to 50 IU/kg, terminal half-life, and incremental recovery at 30 minutes.
Compare PK of FIX products using modeling data
Explore PK modeling data comparing Rebinyn® with SHL and EHL FIX products.
Established safety profile
Clinical trials showed 0 inhibitors and thrombotic events in previously treated patients in 5 clinical trials over 13 years.2,5
The formation of inhibitors (neutralizing antibodies) to Factor IX (FIX) has occurred following Rebinyn®. Common adverse reactions (≥1%) in previously untreated patients reported in clinical trials included FIX inhibitors.
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:
- Negrier C, Knobe K, Tiede A, Giangrande P, Møss J. Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B. Blood. 2011;118(10):2695-2701.
- Rebinyn [package insert]. Plainsboro, NJ: Novo Nordisk Inc.
- Ettingshausen C, Hegemann I, Simpson M, et al. Favorable pharmacokinetics in hemophilia B for nonacog beta pegol versus recombinant factor IX-Fc fusion protein: a randomized trial. Res Pract Thromb Haemost. 2019;3(2):268-276.
- 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.
- 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