The safety profile of ALPROLIX® has remained consistent over 4 years

The safety of ALPROLIX has been demonstrated in clinical trial and postmarketing experience

Even with the extended duration of ALPROLIX clinical trials, no new safety issues were observed2

  • The most commonly reported adverse reactions among adults, adolescents, and children aged <12 years were headache, oral paresthesia, and obstructive uropathy

The B-YOND extension trial confirmed

ZERO

inhibitors, vascular thrombotic events, and anaphylaxis2

In postmarketing safety experience with ALPROLIX2:

  • Formation of inhibitors to factor IX has been reported following an administration of ALPROLIX in postmarketing experience, including in previously untreated patients
  • The use of factor IX products has been associated with the development of thromboembolic complications, especially in individuals receiving continuous infusion through a central venous catheter
  • Hypersensitivity reactions have been reported with ALPROLIX in postmarketing experience

ALPROLIX has the longest duration of patient exposure of any extended half-life factor IX on the market2,3

  • ALPROLIX has been studied in 153 adult, adolescent, and pediatric patients for over 17,000 exposure days

Median duration of ALPROLIX exposure through the first B-YOND interim data cut3:

  • 39.5 months for adult and adolescent patients
  • 21.9 months for children aged <12 years

Important Safety Information

CONTRAINDICATIONS: ALPROLIX® is contraindicated in patients who have a known history of hypersensitivity reactions, including anaphylaxis, to the product or its excipients.

WARNINGS AND PRECAUTIONS: Allergic-type hypersensitivity reactions, including anaphylaxis, are possible with factor replacement therapies, and have been reported with ALPROLIX. Discontinue use of ALPROLIX if hypersensitivity symptoms occur, and initiate appropriate treatment.

Formation of neutralizing antibodies (inhibitors) to Factor IX has been reported following administration of ALPROLIX, including in previously untreated patients. Patients using ALPROLIX should be monitored for the development of Factor IX inhibitors. Clotting assays (e.g., one-stage) may be used to confirm that adequate Factor IX levels have been achieved and maintained.

The use of Factor IX products has been associated with the development of thromboembolic complications.

Nephrotic syndrome has been reported following attempted immune tolerance induction in hemophilia B patients with Factor IX inhibitors and a history of allergic reactions to Factor IX. The safety and efficacy of using ALPROLIX for immune tolerance induction have not been established.

ADVERSE REACTIONS: Common adverse reactions (incidence ≥1%) observed in clinical trials were headache, oral paresthesia, and obstructive uropathy.

INDICATIONS:

ALPROLIX is a recombinant DNA derived, coagulation Factor IX concentrate indicated in adults and children with hemophilia B for:

  • On-demand treatment and control of bleeding episodes
  • Perioperative management of bleeding
  • Routine prophylaxis to reduce the frequency of bleeding episodes

Limitation of Use
ALPROLIX is not indicated for induction of immune tolerance in patients with hemophilia B.

References: 1. Fischer K, Kulkarni R, Nolan B, et al. Recombinant factor IX Fc fusion protein in children with haemophilia B (Kids B-LONG): results from a multicentre, non-randomised phase 3 study. Lancet Haematol. 2017;4:e75-e82. 2. ALPROLIX® [package insert]. Waltham, MA: Bioverativ®, a Sanofi Company; 2018. 3. Pasi KJ, Fischer K, Ragni M, et al. Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B. Thromb Haemost. 2017;117:508-518. 4. Powell JS, Pasi KJ, Ragni MV, et al. Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med. 2013;369(24):2313-2323. 5. Data on file, Bioverativ®, a Sanofi Company. 6. Blanchette VS, Key NS, Ljung LR, Manco-Johnson MJ, van den Berg HM, Srivastava A. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2014;12:1935-1939. 7. Iorio A, Fischer K, Blanchette V, et al. Tailoring treatment of haemophilia B: accounting for the distribution and clearance of standard and extended half-life FIX concentrates. Thromb Haemost. 2017;117(6):1023-1030. 8. Diao L, Li S, Ludden T, Gobburu J, Nestorov I, Jiang H. Population pharmacokinetic modelling of recombinant factor IX Fc fusion protein (rFIXFc) in patients with haemophilia B. Clin Pharmacokinet. 2014;53:467-477. 9. Björkman S. Population pharmacokinetics of recombinant factor IX: implications for dose tailoring. Haemophilia. 2013;19:753‐757. 10. IDELVION® [package insert]. Marburg, Germany: CSL Behring GmbH; 2017. 11. AlphaNine® SD [package insert]. Los Angeles, CA: Grifols Biologicals Inc; 2017. 12. BeneFIX® [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals Inc, a subsidiary of Pfizer Inc; 2017. 13. Ixinity® [package insert]. Berwyn, PA: Aptevo BioTherapeutics LLC; 2016. 14. Mononine® [package insert]. Kankakee, IL: CSL Behring LLC; 2016. 15. Profilnine® [package insert]. Los Angeles, CA: Grifols Biologicals Inc; 2013. 16. Rixubis® [package insert]. Westlake Village, CA: Baxalta US Inc; 2016. 17. Rebinyn® [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2017. 18. Powell JS, Pasi KJ, Ragni MV, et al. Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med. 2013;369(suppl):1-14. https://www.nejm.org/doi/suppl/10.1056/NEJMoa1305074/suppl_file/nejmoa1305074_appendix.pdf. Accessed May 2, 2018. 19. Powell J, Shapiro A, Ragni M, et al. Switching to recombinant factor IX Fc fusion protein prophylaxis results in fewer infusions, decreased factor IX consumption and lower bleeding rates. Br J Haematol. 2015;168:113-123. 20. Kaneko Y, Nimmerjahn F, Ravetch JV. Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science. 2006;313:670-673. 21. Shapiro A. Development of long-acting recombinant FVIII and FIX Fc fusion proteins for the management of hemophilia. Expert Opin Biol Ther. 2013;13(9):1287-1297. 22. National Hemophilia Foundation. Digital Hemophilia Treatment Center Monitoring Linked to Significant Reduction in Bleeding Rates. https://www.hemophilia.org/Newsroom/Medical-News/Digital-Hemophilia-Treatment-Center-Monitoring-Linked-to-Significant-Reduction-in-Bleeding-Rates. Accessed June 7, 2018.