Summer 1997 - Factor Nine News
Part I - What is BeneFIX?
BeneFIX is Coagulation Factor IX (Recombinant) and is used in therapy for factor IX deficiency.
How is BeneFIX created and produced?
BeneFIX is produced by recombinant DNA technology and therefore can be produced without using human blood or plasma. Many commonly used drugs have been created by recombinant technology including recombinant Factor VIII, growth hormone and insulin.
Using recombinant technology, Genetics Institute, Inc. has been able to identify the gene for human Factor IX, copy it (known as cloning) and insert the copied genes into special production cells Once the genes are inserted into the production cells, (through a process known as recombination) genes instruct the cells to begin producing factor IX. As the production cells grow and multiply, they produce the factor IX protein that ultimately becomes BeneFIX. The type of production cells used to produce BeneFIX has been used to produce a large number of commercially available pharmaceutical products over the past decade. These recombinant products have been used for more than 100 million treatments without a single report of viral transmission. In addition to hemophilia, recombinant products are currently used to treat diabetes, anemia, multiple sclerosis, cystic fibrosis, heart attacks and more.
What is a production cell?
The Production cells are the factories for making BeneFIX and other recombinant therapeutics.The production cells used to produce BeneFIX are called Chinese Hamster Ovary or CHO cells. Like the discovery of penicillin, the discovery of CHO cells to produce recombinant proteins involved a stroke of luck. CHO cells have been used since the 1950s by scientists who were studying cell genetics. At the start of the development of recombinant technology, these cell lines were available for experimentation. These CHO cells have been an excellent choice for the production of recombinant proteins for the following reasons:
- Well-established viral safety history
- Products made by CHO cells have been used worldwide without a single report of viral transmission
- Ability to grow and produce without the addition of added human or animal serum
- No blood or plasma products are added to the BeneFIX production process
- Ability to consistently produce a complex protein like factor IX
- The recombinant factor IX made by CHO cells has the identical amino acid sequence as that of
plasma-derived factor IX
Unlike plasma-derived products, BeneFIX is created and produced without blood, plasma, or albumin. Plasma-derived products rely on thousands of blood and plasma donors who are needed for its manufacture. The source of BeneFIX is the production cell containing the clone of the factor IX gene.
This insures that BeneFIX will be free from blood-borne viruses and pathogens such as hepatitis, HIV and parvovirus.
Cost and Dosage amounts
According to The Hemophilia Services Consortium Inc. in New York City current prices for covered entities is 76 cents per unit. Prices may vary according to where product is purchased.
Dosing should be based on the reported clinical trial pharmacokinetic results for BeneFIX. The following formula has been provided as a guide to empirical dosage calculations from the package insert:
number of body desired
factor IX = weight x factor IX x 1.2
IU required …….. (in kg) increase (%) IU/kg
As indicated in the package insert dosage and duration of treatment for all factor IX products depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition, age and recovery of factor IX. For all these reasons doses administered should be titrated to the patient’s clinical response and, when clinically indicated, factor IX activity recovery levels.
For more information please call Genetic Institute’s toll free number at 888-999-2349, visit their Internet site - http://www.genetics.com or E-mail - info@genetics.com.
An inhibitor is an antibody. Antibodies form to destroy substances they do not recognize in the body. Inhibitors form as a response to the Factor IX being recognized as a foreign protein. Inhibitors are more likely to develop among patients with severe hemophilia B than among those with moderate or mild hemophilia B.
Inhibitors to factor IX arise in about 3% of persons with severe hemophilia B, which is less common than the incidence of inhibitors to factor VIII in persons with severe hemophilia A.
When is someone likely to get inhibitors?
Historically, inhibitors are more likely to develop during childhood at the first 10-20 exposure days to factor products.
Does the rate of inhibitor formation vary among the types of products used?
Inhibitors to Factor IX do not seem to be correlated with the type of product used. Inhibitors have developed after treatment with plasma, with prothrombin complex concentrates (PCCs) and with high-purity plasma derived concentrates. A study is ongoing to assess inhibitor formation with recombinant factor IX.
Is there a difference between Factor VIII and Factor IX inhibitors?
Inhibitors to factor IX can sometimes be associated with additional serious complications which have not been observed for inhibitors to Factor VIII. The reaction between factor IX and its inhibitor may cause severe allergic reactions which can be a life-threatening anaphylactic response. These reactions can occur at the first infusion after the development of an inhibitor before it has been detected. For this reason, some doctors are recommending that babies be treated at the clinic until the likelihood of developing an inhibitor is low. While the development of inhibitors to Factor IX is rare and the occurrence of severe allergic reaction is even more rare, parents of infants and toddlers should be aware of those reports of anaphylactic reactions in factor IX inhibitor patients.
Can development of an inhibitor be predicted?
A development of an inhibitor to factor IX can be predicted, at least in part, by determining the kind of factor IX gene mutation the baby has. If he has a major mutation, such as deletion of most or all of the gene, he is much more likely to develop an inhibitor than if he has a simple, minor mutation. Soon it will be standard practice to characterize the mutation as soon as hemophilia B is diagnosed. If the mutation is already characterized in one hemophiliac member of the family, then one may assume that other affected members have the same mutation.
What should be done?
The mutation should be characterized in all families with hemophilia B.
Babies may be treated in a clinic or doctor’s office setting, where medications are available to treat any reaction, until the likelihood of inhibitor development is so low that home treatment can be permitted.
Hemorrhages in patients with hemophilia B who do develop inhibitors may be treated with prothrombin complex or activated prothrombin complex under medical supervision, to see whether these concentrates, which contain factor IX, are tolerated. If patients have allergic reaction to such concentrates, they should be treated for hemorrhages with activated factor VII.
Note: The information above has been summarized from two articles on Inhibitors. One was written by Carol Kaspar, M.D. and the other by Donna M. DiMichele, M.D. Copies of these articles will be
available upon request.
Five $5,000 awards were granted to the following individuals:
Nathan Blackford, Newburgh, Indiana
Attending University of Southern Indiana
Shane Jewell, Bellingham, Washington
Will be attending Oberlin College
Derek Houser, Bruceville, Texas
Attending Baylor University
Stephen Brown, Hamilton, Ontario, Canada
Attending University of Geulph
Zachary Walker, Rexburg, Idaho
Attending University of Idaho
Information on the 1997-1998 program will be available within the next couple of months.
We will keep you updated in future issues of Factor Nine News.
Note: An article featuring the college scholarship winners will appear in NHF’s Community Alert
(September Issue).
Josh Valence is very interested in putting together a support group for individuals with hemophilia in the Florida area. Josh is 34 years old and a severe factor IX hemophiliac. If you are open to the possibility of helping Josh to form this support group, please call him at (561) 540-8685.
For back issues of the Factor Nine Newsletter or for more information on research please call or write to Kim Phelan, 712 Fifth Avenue, 43nd Floor, New York, NY 10019, Telephone (212) 554-6823 Telefax (212) 554-6900. We are now on the Web - our web site number is http://www.coalitionforhemophiliab.org/ E-Mail info@coalitionforhemophiliab.org
About this entry
You’re currently reading “Summer 1997 - Factor Nine News,” an entry on The Coalition for Hemophilia B
- Published:
- 06.10.97 / 6pm
- Category:
- Newsletter
No comments
Jump to comment form | comments rss [?] | trackback uri [?]