Winter 1996 - Factor Nine News

FACTOR NINE NEWS

Prophylaxis is best started at a young age before there is any significant joint damage, usually right after the first bleeding episode. However, there is usually some benefit for patients of any age. The primary benefit is a significant reduction in damage to the joints due to the prevention of joint bleeds. The primary disadvantage is the large amount of Factor IX used. However, some experience from Europe indicates that the total lifetime medical cost of prophylactic treatment is actually lower due to the better overall health of the patient.

The session also presented some of the more practical problems in prophylactic treatment many of which fall on the parents who usually have to deal with giving the daily injections. One real problem is access to the patient’s veins for the daily injections. With small children, age 3 or less, it is very difficult to make injections directly into the veins. Instead a tube or catheter is usually inserted semi-permanently into one of the child’s veins and the injections are made through that. However, these catheters can easily become infected. The parents must be well trained in the proper procedures and hygiene to minimize the chances of infection. In spite of such problems, prophylaxis will probably become much more widely practiced, to the patient’s benefit.

Another session at the NHF meeting focused on inhibitors. Inhibitors are antibodies that attack Factor IX. Because Factor IX is not a normal protein in the hemophiliac’s body, his immune system can see it as a foreign material that it must defend the body against. The body produces antibodies that attach themselves to Factor IX molecules and keep them from working. The occurrence of inhibitors in hemophilia B patients is low, approximately 2% of all hemophilia B patients develop them according to one study, but the consequences can be severe. Although in most cases the major problem is the loss of effectiveness of the Factor IX, one paper presented at the meeting reported on severe allergic reactions that have occurred without warning in a very small number of patients. Because inhibitors usually develop in young children when they are first being treated, and because a severe allergic reaction can be life-threatening without immediate treatment, it was recommended that a child’s first several injections be given at a medical center.

Fortunately, a number of treatments are being developed for patients with inhibitors. Currently most inhibitor patients are treated with Factor IX Complex or with a specially activated Factor IX Complex. As we have discussed before, a side effect of Factor IX Complex is that it can cause the blood to clot too easily, which can be dangerous if clots form in the wrong place. That is why many patients are treated with the more purified Coagulation Factor IX which does not cause this unwanted clotting. However, this extra clott ability can help an inhibitor patient stop a joint bleed when it otherwise would not stop at all. A newer product for inhibitor treatment is a genetically-engineered activated Factor VII. Factor VII is one of the additional clotting factors in some Factor IX Complexes and may be one of the things that helps the complex cause clotting. This new activated Factor VII has shown excellent results in several clinical studies in inhibitor patients. Activated Factor VII is not licensed yet in the U.S. but it is available under special arrangements for treating life-threatening bleeds.

Immune tolerance is another inhibitor treatment method that is being studied extensively. Basically inhibitor patients are given daily injections of clotting factor for an extended period of time, often a year or more. No one understands just why, but in many patients this will cause the inhibitor to eventually disappear. It is almost as if the immune system is overwhelmed and give up trying to fight off the “foreign invader”. So far, not enough hemophilia B patients with inhibitors have been treated to be able to tell how well it works, but immune tolerance has been very successful in treating hemophilia A patients with inhibitors.

Finally we want to mention a couple of new Factor IX products under development which were discussed at the meeting. A recombinant Factor IX which is made by genetic engineering, not purified from blood, is currently in clinical trials and showing good success. This product which is not yet licensed in the U.S. should be extremely safe. Farther away is recombinant Factor IX made in transgenic animals. Recombinant or genetically engineered proteins are made today by putting a gene for a protein like Factor IX, for instance, into bacteria or yeast which causes them to produce Factor IX. Large amounts of these organisms are then grown up in big tanks and the Factor IX they produce is collected and purified. This is a lot like making beer except that the yeast produce Factor IX instead of alcohol. With transgenic animals, the Factor IX gene is put into large animals like cows or goats in such a way that they produce the factor IX in their milk. The milk is collected and the Factor IX is purified from it. A transgenic Factor IX should be as safe as today’s recombinant products. The big advantage of transgenics is that because of the huge amount that can be produced in milk, they should also be much less expensive.

A medical advisory panel convened by the U.S. Food and Drug Administration (FDA) unanimously recommended on December 12, 1996 that the agency license BeneFIX^TM , Coagulation Factor IX (Recombinant), the first recombinant blood clotting therapy for hemophilia B. Developed and manufactured by Genetics Institute, Inc. through biotechnology, plasma-free, albumin-free BeneFIX eliminates the risk of transmitting blood-borne viruses such as hepatitis which have been associated with Factor Ix therapies from human plasma. Genetics Institute’s latest news releases are available at no charge by dialing 1-800-758-5804, ext 352875, or on the internet at http://www.prnewswire.com.

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