The extravascular distribution of endogenous factor IX in Hemophilia B |ALPROLIX® Professional

The extravascular distribution of endogenous factor IX may be a relevant consideration for infused factor IX therapies

Extravascular distribution may have implications on how we evaluate PK activity in hemophilia B, including trough levels^1,2

Multiple PK parameters should be considered, including half-life, clearance, and volume of distribution (VOD)³

Trough levels do not account for infused factor IX that has moved outside of the plasma^4,5

Data in hemophilia B patients show that plasma factor IX levels decrease quickly following infusion⁶

Additional research is needed to understand the clinical implications of VOD

Though PK is important, factor IX replacement therapy should ultimately be evaluated based on outcomes, including bleed prevention and control.

PK parameters, such as trough levels, are not patient outcomes^3,7

Preclinical data are not correlated with outcomes. Animal studies may not apply to humans.
Additional research for preclinical data and research in humans is needed to confirm these findings.

PK=pharmacokinetic.

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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.

Important Safety Information

Contraindication

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.

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Indication

Important Safety Information

References: 1. Feng D, Stafford KA, Broze GJ, Stafford DW. Evidence of clinically significant extravascular stores of factor IX. Thromb Haemost. 2013;11(12):2176-2178. 2. Berntorp E, Dolan G, Hermans C, Laffan M, Santagostino E, Tiede A. Pharmacokinetics, phenotype and product choice in haemophilia B: how to strike a balance? Haemophilia. 2014;20(suppl 7):1-11. 3. 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. 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. Iorio A, Edginton AN, Blanchette V, et al. Performing and interpreting individual pharmacokinetic profiles in patients with Hemophilia A or B: rationale and general considerations. Res Pract Thromb Haemost. 2018;2:535-548. 6. Shapiro AD, Ragni MV, Valentino LA, et al. Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients. Blood. 2012;119(3):666-672. 7. Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1-e47.

Extravascular distribution

The extravascular distribution of endogenous factor IX may be a relevant consideration for infused factor IX therapies

Extravascular distribution may have implications on how we evaluate PK activity in hemophilia B, including trough levels1,2

Though PK is important, factor IX replacement therapy should ultimately be evaluated based on outcomes, including bleed prevention and control.

Explore Half-Life extension with Fc Fusion

Indication

Important Safety Information

Contraindication

Warnings and Precautions

Adverse reactions

Indication

Important Safety Information

Extravascular distribution may have implications on how we evaluate PK activity in hemophilia B, including trough levels^1,2