Factor Nine News

The Coalition for Hemophilia B

DENTAL CARE FOR PATIENTS WITH HEMOPHILIA B

Good dental care is as important for hemophilia B patients as it is for everyone else, probably even more so. Over the past few years it has become apparent that a person's oral health can have a large effect on their overall health. For instance, gum disease may be linked to heart disease, high blood pressure and stroke. There is no reason to avoid taking good care of your teeth because of hemophilia. In fact, because poor dental health can lead to conditions that can cause serious bleeding. It is very important for hemophilia patients to take good care of their teeth and gums.

The primary problems that can arise with your teeth are decay (cavities), gum disease, tooth loss because of accidents, and erosion or wearing down of the teeth caused by acidic drinks, grinding of the teeth or brushing too hard. Tooth loss, whether intentional because of severe decay or erosion or unintentional because of accidents, always involves bleeding. Gum disease causes bleeding by itself and can also lead to tooth loss if the disease becomes severe.

Good dental health begins with regular dental care, brushing, flossing and regular visits to the dentist. It is important to practice good oral hygiene at home every day. Brushing your teeth and flossing daily are the major steps to healthy teeth and gums. Brushing and flossing can cause bleeding, but over time it actually toughens your gums leading to less bleeding in the long run. However, if bleeding continues for more than 20 minutes or if it stops and then starts again, you should consult your physician. Hemophiliacs with joint disease that keeps them from brushing and flossing effectively can often benefit from toothbrushes with special handles, electric toothbrushes and floss holders.

Your diet can also have a major effect. Sugar and acidic drinks, like sodas and fruit juices, are particularly bad for your teeth. This is especially true for between-meal snacks when there is no other food to help neutralize the acid and keep the sugar from coating the teeth. It is better to have fresh fruit, but not fruit juices, or other low sugar foods as snacks. Interestingly, although many kinds of fruit are acidic and contain sugars, fresh fruits do not appear to cause tooth decay.

Gum disease (gingivitis) usually results in bleeding, which can be a significant problem for a hemophilia patient. Factor treatment can temporarily stop the bleeding but does nothing to stop the disease.

"Patients on prophylaxis should schedule their visits for days when they infuse factor."

Severe gum disease can lead to loosening or loss of teeth. Gum disease is caused by plaque, a bacterial film that forms on the teeth and irritates the gums. Gum disease can be aggravated by smoking and by immune depression associated with HIV infection. Plaque can be removed by brushing and flossing. If it is not removed at least daily, it hardens into tartar, which can only be removed by a dentist or hygienist.

It is important to establish a relationship with a dentist who is willing to accommodate the special needs of the patient with hemophilia. Many hemophilia treatment centers have dentists on staff or know local dentists who have experience treating hemophilia patients. If your dentist is not familiar with hemophilia, but is interested in treating you, have him or her contact your hemophilia treatment center or physician for advice. Some dentists may even be overly concerned with your condition and need reassurance. In any case, your dentist should know whom to contact with questions about your treatment and for access to your medical records, if needed. Inform your dentist if you are on a prophylactic therapy and how you treat a minor bleeding episode.

It is important to make regular visits to your dentist. This helps keep small issues from turning into larger problems. Making regular visits helps you to avoid things like emergency root canals and extractions and is generally more cost-effective in the long run. How often you visit should be discussed with your dentist. Older patients with gum disease, for instance, will probably need more visits than a young person who practices good oral hygiene. Patients on prophylaxis should schedule their visits for days when they infuse factor.

Unless your teeth and gums are in excellent shape, almost any dental procedure, even cleaning, results in bleeding. Therefore, patients with moderate or severe hemophilia will need to infuse factor immediately prior to their visit. Patients with catheters or artificial joints may also need to take antibiotics because small amounts of bacteria that may be introduced into the bloodstream during dental procedures tend to accumulate on foreign objects in the body, and infections on implants are hard to treat.

Treatment of bleeding in the mouth requires extra care. Because the inside of the mouth is wet, clots have a harder time forming and sticking to the underlying tissue. Clots that do form can be easily dislodged. For instance, sucking on a straw can also suck a clot away from a bleeding site. Because of this, bleeds are sometimes treated with antifibrinolytic drugs such as aminocaproic acid (Amicar) or tranexamic acid (Cyklokapron), in addition to factor therapy.

A short medical lesson: Fibrin is the protein that forms a clot. Lysis means dissolving or loosening. Thus something that breaks down a clot is a fibrin-o-lytic. A drug that prevents the breakdown is anti-fibrin-o-lytic. Just as there are enzymes in the body, such as Factor IX, that cause the blood to clot, there are also enzymes that break down clots as an injury heals. These are fibrinolytic enzymes. However, if the bleeding is prolonged or the tissue is re-injured, the clot breakdown process can proceed before there is enough new tissue to keep the injury from bleeding. The purpose of an antifibrinolytic is to slow down the clot breakdown process until enough new tissues are formed. Additional resources can be found at:

http://www.wfh.org
http://hemophiliagalaxy.com

BENEFIX - HOW IT BEGAN

The long development of BeneFIX began in the early 1980's when the factor IX gene was identified, then continued through the efforts of many scientists in San Diego and Boston, and finally was completed by several forward-seeing business risk-takers at Genetics Institute (GI) who bet their company to get this product to market.

Wyeth financed the final hurdles, merged with GI and today has spread BeneFIX around the world. Even if you don't use BeneFIX, the scientific advances that this team made have improved our community's future. What follows is a history jotted down from memory, and we apologize to those who are not mentioned because of our poor memory or lack of knowledge. BeneFIX is a project that has involved thousands of dedicated professionals and still involves many today. We thank them all.

After the isolation of the factor IX gene some 25 years ago in San Diego, the scene shifts to Boston, where many scientists worked to produce a reombinant factor IX. Dr. Randy Kaufman was critical in its development but Drs. Barbara and Bruce Furie among others were important in the final outcome. Many, many problems were overcome and Genetics Institute who had just developed a recombinant factor VIII as well financed the project. Some problems proved almost intractable and the activity of the factor IX transgenic molecule was very hard to regulate. And it was expensive to produce. The fine-tuning of BeneFIX took years, and a tremendous amount of money. "Even though we knew a great deal about manufacturing a recombinant molecule, there were several unique and daunting hurdles associated with producing the factor IX molecule," said Hubert Scoble, Assistant Vice President, Wyeth BioPharma Development "The principal achievement was determining how to obtain a high level of expression of factor IX. That and other innovations allowed us to create an economically viable product for the company and the community."

Anyone following the financial fortunes of GI during that period watched a roller-coaster ride and the company was at risk of dying. In 1994, the critical decision was made to go ahead. The fear was that this very expensive project might fail because gene therapy would make recombinant factor IX a white elephant by the time the FDA approved it.

The project was entrusted to John Edwards, who did a brilliant job of pushing this product through trials and the FDA approval process in an incredibly short time. Working for John and overseeing the trials was a woman, Soozie Courter, who was truly unforgettable. Everyone knew her, she had time to listen to everyone - doctors, scientists, FDA inspectors, patients, parents, everyone - and at the same time she ran a trial that had no errors. Soozie was amazing and we all owe a great deal to her for her love of us and her scientific prowess. Soozie, is gone but Wyeth has established a scholarship fund in her memory. No one is more worthy.

Three short years after filing its application, the U.S. Food and Drug Administration granted approval to market BeneFIX -- the first product to be produced without human blood donors or animal proteins. "The development of BeneFIX was a perfect combination of circumstances. We were able to do the right thing for the community by creating a recombinant factor IX product, and do the right thing for the company by creating a product that could be called a biopharmaceutical first," said Michael P. Russomano, Jr, VP & Global Business Manager - Hemophilia. "It's not often that you can become involved in work that is so personally rewarding and scientifically challenging. We are fortunate to be part of the hemophilia community and to see the impact of our efforts to create products that offer improved hemophilia care," Russomano added.

We are lucky to have this product with us today, and those who went through the trials and watched as GI tried to reach its goal have a very special memory. Anyone who would like to add to our thoughts here, please send them to us and we will put them in a future letter. It's a good thing to tell our children about what it takes to develop a miracle drug. ~

ON THE RESEARCH FRONT...

Avigen announced it will discontinue its development of a gene transfer therapy for hemophilia. Avigen's decision to end its hemophilia drug trials were announced in a company press release. The statement quoted Glenn Pierce, PhD, MD, Avigen's vice president of research and clinical development and former NHF president, who explained that "Due to certain scientific, regulatory and clinical hurdles we believe are specific to hemophilia, discontinuing the Coagulin-B trial makes the best strategic sense at this point." Pierce went on to say that Avigen and its partner, Bayer HealthCare, have "made significant progress in establishing proof of principle that hemophilia gene therapy could work in the clinic."

The National Hemophilia Foundation (NHF) remains optimistic about the potential for gene transfer and other investigational therapies for hemophilia and will continue to support such research. "We are confident that breakthroughs in recent years and those to come, will lead us to a cure for bleeding disorders," said NHF President Richard Metz, MD. "This is a time to redouble our efforts to support promising research so that breakthroughs for hemophilia and all genetic disease will happen sooner, nor later," Metz said. ~

VCJD RISK ANNOUNCED FOR U.K. PLASMA PRODUCTS

On September 21, 2004, United Kingdom (UK) health authorities informed people with hemophilia and other bleeding disorders that they are considered "at risk" for variant Creutzfeldt-Jakob Disease (CJD) if they used UK plasma products manufactured between 1980 and 1998. These products were made from plasma collected from donors, in the UK who were later identified to have vCJD or possibly from donors who still remain asymptomatic for vCJD.

The UK's products were manufactured by Bio Products Laboratory and Protein Fractionation Centre, Scotland. These companies were not licensed by the US Food and Drug Administration (FDA) to distribute products in the United States, but UK plasma products, particularly factor XI, may have been brought into the US for use in clinical trials or for compassionate or personal use. FDA has not approved any manufacturing claim that the production process for any plasma-based coagulation products eliminates the risk of vCJD transmission. However, to date, no cases of vCJD are known to have been transmitted by any plasma product. The UK health authorities have said their actions are precautionary and the actual risk is very low.

Additional information can be found at:
http://www.wfh.orgShowDoc,asp?Rubrique=30&Document=37
http://www.hemophilia.ca/en/index.html

ZLB BEHRING INDUSTRY SPONSORED SYMPOSIUM

in conjunction with the
COALITION FOR HEMOPHILIA B FAMILY FORUM MEETING

Breakfast Meeting
Saturday, November, 6, 2004
7:00 am - 9:00 am
Reunion Ballroom C (Lobby Level)
Hyatt Regency Dallas at Reunion Center
300 Reunion Blvd.
Dallas, Texas
(214) 651-1234

We look forward to seeing you!

TOPIC: THE ROAD TO RECOVERY: CHOICES FOR HEMOPHILIA B
7:20 AM - 8:15 AM

Speaker: Dr. Jorge DiPaula, Assistant Professor of Pediatrics and Director, Hemophilia Treatment Center, University of Iowa.

Program Description: The program will provide an overview and discussion of the various treatment options available for hemophilia B. The history, manufacturing processes, and pros and cons of each FIX product on the market will be discussed. Q & A/ open forum will follow the presentation.

Factor Nine Family Meeting Follows, 8:20 AM - 9:00 AM

Babysitting will be provided by the Youth and Adolescent program beginning a few minutes before 7 am. Children must be pre-registered for the Y&A program in order to be eligible for babysitting services. If you have small infants and want to bring them to the meeting, please do. If you have any questions please call Kim at (212) 554-6898 or email: hemob@ix.netcom.com