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Consistent Pharmacokinetic Profile

One IU of AlphaNine SD infused per kg of body weight raises the recipient's plasma Factor IX level by 1%.

Summary of the pharmacokinetic parameters of AlphaNine SD1

Parameter PK1 Mean (±SD) (n = 25) PK2 Mean (±SD) (n = 23)
Recovery (IU dL-1 per IU kg-1 1.01 ± 0.19 1.23 ± 0.34
Terminal half-life (t1/2) (h)* 34.5 ± 6.2 33.7 ± 5.4
Area under the curve (AUC0-74h) (IU x h dL-1) 1351.8 ± 260.7 1442.0 ± 246.1
Area under the curve (AUC0-∞) (IU x h dL-1) 1601.6 ± 312.1 1643.7 ± 360.0
Clearance (CL) (dL min-1) 0.076 ± 0.02 0.071 ± 0.01
Mean residence time (MRT) (h) 35.76 ± 5.4 34.63 ± 5.2

Results from a pharmacokinetic, efficacy and safety study in 25 severe hemophilia B patients treated with AlphaNine SD, which compared the first AlphaNine SD pharmacokinetics with a second assessment after 6 months of treatment.1


AlphaNine SD was infused at a single dose of 65-76 IU/kg and FIX activity was determined at pre-infusion and different times until 74 hours post-infusion.1


Comparision to Recombinant Factor IX

In an extension of the study described above, 22 patients also completed a pharmacokinetic analysis using a single 61.5-75.0 IU/kg dose BeneFIX® [Coagulation Factor IX (Recombinant)]. Over 72 hours, recovery of BeneFIX (1.00 IU dL-1 per IU kg-1) was lower than recovery of AlphaNine SD (1.30 dL-1 per IU kg-1).2


Summary of the pharmacokinetic parameters of AlphaNine SD and BeneFIX2

Parameter AlphaNine SD (n=25)* BeneFIX (n=22)
Recovery (IU dL-1 per IU kg-1) 1.30 ± 0.4 1.00 ± 0.3
Terminal half-life (t1/2)(h) 32.7 ± 7.4 36.0 ± 12.8
Area under the curve (AUCO-∞)
(IU x h dL-1)
1684 ± 425 1631 ± 467
Clearance (dL kg-1 h-1) 0.042 ± 0.01 0.046 ± 0.01
Mean residence time (MRTO-∞) (h) 31.7 ± 6.4 39.3 ± 13.9
Volume of distribution (VdSS)
(dL kg-1)
1.34 ± 0.42 1.75 ± 0.52

These results confirm the differences in the pharmacokinetic profiles of BeneFIX and plasma-based FIX products, including AlphaNine SD, that have been consistently observed in previous studies. The lower recovery means that BeneFIX must be administered at proportionally higher doses and more frequent intervals to achieve the FIX concentrations considered to be hemostatic. This difference has limited the creation of consistent dosing guidelines and caused the manufacturer of BeneFIX to recommend regular pharmacokinetic assessments and close monitoring of FIX plasma levels before elective surgical procedures, establishing prophylactic regimens, or switching FIX products.2   


Indications

AlphaNine® SD (coagulation factor IX [human]) is indicated for the prevention and control of bleeding in patients with Factor IX deficiency due to hemophilia B.


AlphaNine SD is made from human plasma. Plasma products carry a risk of transmitting infectious agents, including viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent, despite steps designed to reduce this risk.

Incidences of thrombosis or disseminated intravascular coagulation (DIC) have been reported following administration of Factor IX Complex concentrates which contain high amounts of Factor II, VII and X. AlphaNine SD contains low, nontherapeutic levels of Factor II, VII and X.

Following administration in surgery patients and individuals with known liver disease, the physician should closely observe the patient for signs and symptoms of potential disseminated intravascular coagulation.

Allergic type hypersensitivity reactions, including anaphylaxis, have been reported for all factor IX products. The administration of plasma preparations may cause allergic reactions, mild chills, nausea or stinging at the infusion site.

Nephrotic syndrome has been reported following attempted immune tolerance induction with factor IX products in hemophilia B patients with factor IX inhibitors and a history of severe allergic reactions to Factor IX.

In order to minimize the possibility of thrombogenic complications, dosing guidelines should be strictly followed.

AlphaNine SD should not be administered at a rate exceeding 10 mL/ minute. Rapid administration may result in vasomotor reactions.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see full Prescribing Information for AlphaNine SD.


Reference

  1. Lissitchkov T et al. Haemophilia. 2011;17(4):590-596.
  2. Lissitchkov T et al. Haemophilia. 2013;19(5):674-678.