General Information

Rebinyn is a proprietary glycopegylated recombinant factor IX for patients with hemophilia B.

Rebinyn is specifically indicated for use in adults and children with hemophilia B for on-demand treatment and control of bleeding episodes and for the perioperative management of bleeding.

Rebinyn is supplied as a lyophilized powder for solution for intravenous injection. The recommended dose for on-demand treatment and control of bleeding episodes is 40 IU/kg body weight for minor and moderate bleeds, and 80 IU/kg body weight for major bleeds. Additional doses of 40 IU/kg can be given. The recommended dose for perioperative management: Pre-operative dose of 40 IU/kg body weight for minor surgery, and 80 IU/kg body weight for major surgery. As clinically needed for the perioperative management of bleeding, repeated doses of 40 IU/kg (in 1-3 day intervals) within the first week after major surgery may be administered. Frequency may be extended to once weekly after the first week until bleeding stops and healing is achieved.

Clinical Results

FDA Approval

The approval of Rebinyn was based on four multicenter, non-controlled trials (the PARADIGM program) which were conducted to evaluate the safety and efficacy of Rebinyn in routine treatment, on-demand treatment and control of bleeding episodes, and perioperative management in previously treated male patients with hemophilia B (Factor IX activity ≤ 2%). The efficacy evaluation included 105 subjects: 62 adults (18 to 65 years old), 18 adolescents (13 to 17 years old), and 25 children (1 to 12 years old). • Adult/adolescent trial: The trial included 74 adolescent and adult previously treated patients. There were two routine treatment arms, with single-blind randomization to either 10 IU/kg or 40 IU/kg once-weekly for approximately 52 weeks, and an open-label on-demand treatment arm for approximately 28 weeks. • Surgery trial: The surgery trial included 13 previously treated adolescent and adult patients who received one infusion of Rebinyn 80 IU/kg on the day of surgery, and post-operatively received infusions of 40 IU/kg, at the investigator’s discretion, for up to 3 weeks after surgery. • Adult/adolescent extension trial: There were 71 subjects from the adult/adolescent trial and surgery trial who continued routine treatment or on-demand treatment with Rebinyn in an open-label extension trial, with the possibility to switch regimens during the trial. • Pediatric trial: The main phase of the pediatric trial included 25 pediatric previously treated patients (1-12 years old) in which subjects received routine treatment with Rebinyn 40 IU/kg once-weekly for approximately 52 weeks.

Treatment of Bleeding Episodes: A total of 597 bleeding episodes were reported in 79 out of 105 subjects in the clinical program in previously treated patients. Bleeding episodes were treated with Rebinyn at 40 IU/kg for minor or moderate bleeds or 80 IU/kg for major bleeds, with additional doses of 40 IU/kg as needed. The median dose to treat a bleeding episode was 42.3 IU/kg. An overall assessment of efficacy was performed by the subject (for home treatment) or the study site investigator (for treatment under medical supervision) using a 4-point scale of excellent, good, moderate, or poor. The overall success rate (defined as excellent or good) for treatment of bleeding episodes was 93.2%. In the on-demand arm there were 143 bleeding episodes in 14 of 15 subjects. The overall success rate was 95.1% (135 of 142 evaluated bleeds). A total of 120 bleeds (83.9%) of the 143 bleeding episodes were treated with one injection, and 20 (14.0%) were treated with two injections.

Perioperative Management In the surgery trial: The efficacy analysis of Rebinyn in perioperative management included 13 surgical procedures of which 9 were major and performed in 13 previously treated adolescent and adult patients. The procedures included 9 orthopedic, 1 gastrointestinal and 3 in the oral cavity. The hemostatic effect during surgery was evaluated on a four-point scale of excellent, good, moderate, or poor. The intraoperative hemostatic effect was rated as excellent or good for the 13 surgeries, for a success rate of 100%. A preoperative dose of 80 IU/kg Rebinyn was effective, and no subjects required additional doses on the day of surgery. The median number of additional 40 IU/kg doses in the post-operative period was 2.0 for Days 1 to 6, 1.5 for Days 7-13, and 3.0 for Days 1 to 13. The mean total consumption of Rebinyn in the pre- and post-operative period was 241 IU/kg (range: 81 to 460 IU/kg). There was no unexpected postoperative bleeding. Three additional major surgeries and 18 minor surgery procedures were evaluated in the extension trial for Rebinyn in previously treated patients. The hemostatic effect during major and minor surgery was confirmed with a success rate of 100%.

Mechanism of Action

Rebinyn is a proprietary glycopegylated recombinant factor IX for patients with hemophilia B. Glycopegylation is a well-established protraction technology applied by Novo Nordisk on recombinant factor IX. The technology increases the circulating half-life of recombinant factor IX allowing for lower bleeding frequency with less frequent intravenous dosing.