How it works
PEGylation is an established technology used to extend half-life and maintains elevated Factor IX (FIX) levels.1 The Factor IX in Rebinyn® is conjugated to a 40-kDa polyethylene glycol molecule, which slows down its removal from the blood circulation.2
Selective Attachment
PEG selectively attaches to the FIX activation peptide by site-directed glycoPEGylation3
Prolonged Circulation
GlycoPEGylation keeps Rebinyn® in the bloodstream longer where it needs to be to stop bleeding3
Activated FIX Release
Rebinyn® releases rFIX similar to native human FIX once activated2
Adverse reactions
Animals administered repeat doses of 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.2
Powerful bleed protection
Studies show Rebinyn® prophylaxis helps prevent spontaneous and traumatic bleeds.2
Established safety profile
Clinical trials showed 0 inhibitors and thrombotic events in previously treated patients in 5 clinical trials over 13 years.2,4
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.
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:
- Swierczewska M, Lee KC, Lee S. What is the future of PEGylated therapies? Expert Opin Emerg Drugs. 2015;20(4):531-536.
- Rebinyn [package insert]. Plainsboro, NJ: Novo Nordisk Inc.
- Østergaard H, Bjelke JR, Hansen L, et al. Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide. Blood. 2011;118(8):2333-2341.
- 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