Watch Video Now Icon WATCH NOW: Clinical experience with ALPROLIX

Fc Fusion allows ALPROLIX® to mirror the pathway followed by endogenous factor IX

  • VOD is a PK parameter that quantifies the movement of infused factor IX between the intravascular and extravascular spaces1
  • ALPROLIX has a high* VOD—327 mL/kg for a 50 IU/kg dose—which suggests that it travels to areas of the body outside the intravascular space, similar to endogenous factor IX2,3
Blood vessel human graphic

Additional research is needed to understand the clinical implications of VOD.

*Based on the theoretical plasma volume of 40 mL/kg in adults.4

The subgroup receiving 100 IU/kg of ALPROLIX has a reported VOD of 236 mL/kg. The difference in reported values is within normal variation and may be due to intersubject variability. This assessment is based on the adult population; a high VOD has also been observed for children and adolescents at the 50 IU/kg and 100 IU/kg doses.2,8

ALPROLIX molecule icon

Fc Fusion technology is thought to be related to the extravascular distribution of ALPROLIX2-4

  • The extravascular distribution of ALPROLIX, as well as its clearance from the body—3.3 mL/h/kg for a 50 IU/kg dose in adults—help to extend its half-life2,5
  • ALPROLIX also degrades naturally into amino acids and does not accumulate in the body6

This PK profile indicates that trough does not measure all of the ALPROLIX in the body. The ISTH recommends that multiple PK parameters should be evaluated, including half-life, VOD, and clearance1-3,7

ISTH=International Society on Thrombosis and Haemostasis; PK=pharmacokinetic; VOD=volume of distribution.

IMPORTANT SAFETY INFORMATION AND INDICATION

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. 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:

  • The most common adverse reactions (incidence ≥1%) in previously untreated patients were injection site erythema, hypersensitivity, and Factor IX inhibition. The most common adverse reactions (incidence ≥1%) in previously treated patients were headache, oral paresthesia, and obstructive uropathy.

INDICATION:

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.

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References: 1. McNamara PJ, Leggas M. Drug distribution. In: Hacker M, Messer W, Bachmann K, eds. Pharmacology: Principles and Practice. Burlington, MA: Elsevier Academic Press; 2009:113-127. 2. ALPROLIX [package insert]. Waltham, MA: Bioverativ Therapeutics Inc. 3. 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(5):467-477. 4. Iorio A, Fischer K, Blanchette V, Rangarajan S, Young G, Morfini M. 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. 5. Björkman S. Comparative pharmacokinetics of factor VIII and recombinant factor IX: for which coagulation factors should half-life change with age? Haemophilia. 2013;19:882-886. 6. 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. 7. Ragni MV, Croteau SE, Morfini M, et al. Pharmacokinetics and the transition to extended half-life factor concentrates: communication from the SSC of the ISTH. J Thromb Haemost. 2018;16(7):1437-1441. 8. Björkman S. Population pharmacokinetics of recombinant factor IX: implications for dose tailoring. Haemophilia. 2013;19(5):753-757.