FOR ONCE-WEEKLY PROPHYLAXIS
Life is about the unexpected
Rebinyn® delivers higher Factor IX (FIX) levels for longer.1,a Review the Prescribing Information for the latest data.
- FIX levels in the non-hemophilia range for most of the week2,b
- Simple once-weekly dosing3
- Prevents bleeds before they start3
Timothy has severe hemophilia B and uses Rebinyn®.
aBased upon a phase 1 study of patients administered one of three doses of Rebinyn® (25, 50, or 100 IU/kg) compared with one dose of their prior SHL rFIX (n=7) or pdFIX (n=8) at the same dose using a one-stage assay and product-specific standard. Estimated mean pharmacokinetic (PK) parameters are adjusted to a dose of 50 IU/kg. Incremental recovery at 30 minutes (IR30) and half-life were higher and longer with Rebinyn® than rFIX (IR30 0.0131 vs 0.0068 (IU/mL)/(IU/kg) and half-life 93 vs. 19 hours). (All values were statistically significant (P< 0.001).) The clinical relevance of these PK differences is unknown.1
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
Rebinyn® once-weekly helps adults and adolescents maintain FIX levels in the non-hemophilia range for most of the week2,c
Adult and adolescent patients achieved FIX levels in the non-hemophilia range2,c
Adult and adolescent patients achieved FIX levels in the non-hemophilia range2,c
- In adults, the half-life was 115 hours.d Factor IX levels after infusion were 98% and Factor IX levels by Day 7 were 29%.3,e
- In adolescents, the half-life was 103 hours.d Factor IX levels after infusion were 83% and Factor IX levels by Day 7 were 24%.3,e
cData 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
dBased 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).3
eBased on the mean steady-state pre-dose trough levels and post-dose peak levels in previously treated patients (20 adults and 9 adolescent patients) 168 hours after administered Rebinyn® 40 IU/kg once weekly.3
Raise FIX levels so patients can be ready for the unexpected
Factor IX activity
achieved in adults within the first hour after dosing with Rebinyn®3,e
mean Factor IX trough levels
achieved in adults3,e
Timothy lives with hemophilia B.
overall median ABR
in adults, meaning your prophylaxis patients could experience powerful bleed protection3,f
years of clinical trial experience5
fABR of 1 was based on statistical calculation of median ABR for total bleeds in adult patients.6
Simple
once-weekly prophylaxis dosing3
IU/kg
for all ages
Adjust dosing regimen based on individual patient’s bleeding pattern, and physical activity.
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Patient Trial Program
Considering Rebinyn® for your patients with hemophilia B?
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Study designs
Collins et al (2014)7
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 and prophylactic effect of Rebinyn® 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)6
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 and prophylactic effect of Rebinyn® when treating spontaneous or traumatic bleeding episodes. Assessment included number of bleeds and FIX activity.
Selected 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.
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
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.
References:
- Negrier C, Knobe K, Tiede A, et al. 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.
- 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.
- Rebinyn [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2022.
- Srivastava A, Santagostino E, Dougall A, et al. WFH guidelines for the management of hemophilia. Haemophilia. 2020;26(Supp 6):1-158.
- 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
- 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.
- 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.