Pharmacokinetic Innovation Benefits Hemophilia B Patients


  • April 10, 2014

By Dr. Bob Roth, M.D., Ph.D.

Innovation in pharmacokinetics can have dramatic benefits for patients. For example, extended release formulations of drugs given at bedtime can make the difference between needing to awaken for the next dose of drug vs. sleeping all night. Depot injections can have even more impact on dosing intervals, benefitting both drug tolerability and compliance; and innovations such as the creation of pro-drugs can impact bioavailability of poorly absorbed active ingredients. Alprolix™, the recently-approved chemically modified blood product, may also be added to this list. The drug provides a dosing benefit by keeping the drug within the blood stream, where it acts for a longer period of time.

Coagulation factor IX is used to control bleeding in patients with hemophilia B. These patients have deficiencies in blood factor IX, and are at risk for an increased rate of spontaneous bleeding or excessive perioperative bleeding with surgery. The amount of factor IX required to treat and/or prevent bleeding is dependent on how much endogenous factor the patient may have, and whether the clinical intent is to prevent all bleeding or just the risk of potential fatal bleeding. FDA’s approval of Alprolix (recombinant coagulation factor IX, Fc fusion protein) provides a particular benefit to patients with severe hemophilia B (typically factor levels <1% of normal) because the infused protein circulates for a prolonged period of time and dosing can be relatively infrequent. For many patients, weekly or even less frequent dosing may provide adequate prophylaxis compared to prior therapies which would often need to be administered two or three times weekly.

The dosing advantage of Alprolix derives from its manufacture as a fusion protein with a portion of antibody molecules. The antibody component acts as a carrier, creating a drug-carrier complex similar to the product made by linking of factor IX to albumin. The fusion protein has a terminal half-life several times longer than unmodified factor IX molecules. Since substantially improved hemostasis in severe hemophiliacs can be accomplished by maintaining factor IX blood levels above 1-3% of normal, even the relatively low blood concentrations of infused factor during the terminal phase of clearance prove to be clinically beneficial. Less frequent dosing means increased patient convenience, greater cost effectiveness, and potentially fewer infusion reactions and opportunities to produce inhibitors.

Since hemophilia B is a genetic disorder, not much short of gene therapy could be used to “cure” the disease. Rather, clinical focus is on managing the coagulation factor deficiency state to minimize the long-term and acute risks of major bleeding and crippling musculoskeletal consequences. Improved factor replacement products such as Alprolix have the potential to significantly impact cost and effectiveness of controlling hemorrhage in these patients, and as such contribute disease-modifying improvements in clinical practice.

Dr. Bob Roth, M.D., Ph.D. is Vice President & Worldwide Medical Director at The Weinberg Group, the world’s leading food and drug consulting firm. If you have any questions or thoughts on this blog post or others, please contact us