Spring/Summer 2006 - Factor Nine News

TOPICS IN HEMOPHILIA

-Factor Nine Family Meeting, October 14, 2006
-HFA, WFH, Binghamton Chapter Meetings
-FIX Replacement Therapy
-Prophylaxsis Update
-Grifols Donates 1.4 Million in Clotting Therapies

---

Your Invited!

Factor Nine Family Breakfast Meeting

In conjunction with the NHF Annual Meeting

******************************

Saturday, October 14, 2006
8:30 – 9:30 am
Marriott Courtyard Hotel
(located across the street from the Downtown Marriott)
Philadelphia, PA
Salon Room 3
(level 1 right off elevators)

A great place for people with factor IX and their families to get together, gain support,
share stories and make friends.

We learn from each other. New families can gain valuable knowledge from those who have been through the ropes.

Knowledge ~ Resources ~ Peer Support

Empower Yourself and your loved ones!

---

Hemophilia Federation of America Conference

March 31 – April 2, 2006

St. Louis, MOHFA’s annual meeting was a great success this year. Enthusiasm and optimism were very high. Speakers presentations were better attended than ever before. Of particular interest was the Reimbursement Issues Panel facilitated by Jan
Hamilton, HFA Advocacy Director. Speakers
were Patrick Collins, Sr. Manager, Public Affairs, ZLB Behring, Dana Kuhn, PhD, President, Patient Services Inc. (PSI), and Kim Bernstein, Esq, Director, ACCESS Program, Hemophilia Health Services, (HHS). Patrick discussed Medicare and Medicaid Issues, Dana’s topic was on Insurance Trends and Kim informed the audience
about Social Security Issues that affect many in the community. HFA has many organizations working together to keep you updated. If you have any questions, please call Kim Phelan at (212) 554-6898, hemob@ix.netcom.comOur meeting had a good turnout with people from all ages and places! We heard interesting stories about experiences with hemophilia. The group shared their views with each other on treatment options. Friends were made, phone numbers exchanged. The bridge of support keeps growing.

---

Bleeding Disorders of the Southern Tier (BDAST) Conference, Binghamton, NY

April 29, 2006

A good turn out at this conference. Speakers included John Williams, Hemophilia Health Services, Jill Williams, Critical Care Systems, Paul Brayshaw, Rep, HFA, Tom Vaclavik, HFA, Meredith Zerbe, Baxter, John Davis and Wayne Cook as well as representatives from Wyeth, Bayer, Baxter and Grifols. The sessions were Dads in Action, Adult Men’s program. Factor information from the manufacturers, Insurance and Legislation updates. Wives of men with bleeding disorders and Woman with bleeding disorders. On Sunday, a movie was shown “The Unexpected Life”. Also a session on how to smile and have a positive outlook on life. For Saturday Nights event, the chapter held a Hawaiin Luau in the pool area of the hotel.

---

World Federation of Hemophilia

Congress May 21-25, 2006

The meeting was held in the spectacular waterfront setting of the Vancouver Exhibition. Ceremony
audience was treated to a colourful performance by a 30 member pipe band and a first Nations drum group.Sessions were well attended and topics ranged from the latest developments in areas ranging from inhibitors, prophylaxis, to pain management, quality of life, research and family issues. Other sessions also focused on bleeding disorders such as von Willebrands, as well as the challenges for patients in countries with limited economic resources.

---

Close to 4,000 people from more than 100 countries gathered in Vancouver, CanadaThe record number of participants included people with hemophilia, medical professionals, national hemophilia organizations, industry and regulators.

Wayne Cook and Helmut Gast, Germany Representatives for The Coalition for Hemophilia B included Kim Phelan, Wayne and Maureen Cook. We truly enjoyed meeting people all over the world and to finally meet in person, people we have been in correspondence with for years. We had many requests to hold educational workshops worldwide. It was also nice to see people from the community back home in the USA.

Wayne and Maureen Cook Exhibitors showcased the latest hemophilia treatment products, services and publications. Hemophilia associations from various countries held booths at the WFH. A poster display featured numerous contributions from individuals and organizations.~

---

Factor IX Replacement in Surgery

“A pharmacokinetic study tells the physician how much factor IX shows up in the bloodstream (the recovery) and how long it lasts (the half-life

Surgery presents specials issues for hemophilia treatment. Before the advent of modern Factor IX Concentrates, only the most necessary surgical procedures were performed on hemophilia B patients. Elective surgery was rarely considered. For instance, older hemophilia B patients with severe joint damage often had to just live with the pain and disability because joint replacement surgery was too risky. Prior to the introduction of more highly purified factor IX Concentrates in the late 1980s, patients were treated with Factor IX Complex Concentrates, which have the dangerous side effect of inducing thrombosis, unwanted clotting. When used in large doses patients would have successful surgeries, without excessive bleeding, only to end up with serious, even fatal thrombotic complications during their recovery.

It is still not certain why Factor IX Complex cause thrombosis, but todays more highly purified factor IX concentrates seem to be largely free of this side effect. Now hemophilia B patients can even consider elective (non-essential) surgery. An article from Northwestern University discusses a number of issues involved in factor IX replacement, to control bleeding during surgery.

Even though a blood factor level of one to two percent of normal is usually enough to prevent bleeding in everyday life, that is far too little for surgery. Patients are usually brought up to blood levels of 80-100% of normal for surgery. This takes a lot more factor concentrate and more precise dosing. The Northwestern article (Factor IX Replacement in Surgery & Prophylaxis by Anaadriana Zakariji) highly recommends performing a pharmacokinetic study on a patient before surgery, while he is not bleeding.A pharmacokinetic study tells the physician how much of the factor IX infused shows up in the patient’s bloodstream (the recovery) and how long it lasts (the half-life). This helps the physician determine the correct dosage of factor IX to prescribe.

In the past, pharmacokinetic studies were done less frequently and physicians often used general guide-lines in seting the dose for the “average” patient.
However, it is now known that few patients are actually average. Another study of 43 hemophilia B patients found recoveries of factor IX after infusion ranging from 57% to 143% of the average recovery. Looking at the individual patient data, there was not a large group of patients clustered around the average recovery with a few extreme cases. The patients’ recoveries were spread over the whole range, so most of the patients, in fact, were not average. Just going by an average guideline could result in a patient with a low recovery getting too little factor IX to prevent bleeding, while a patient with a high recovery would receive too much, a waste of the expensive product.

Patients will usually stay with the factor IX product they already use successfully for prophylaxis or routine treatment, whether plasma-derived or recombinant. It is very important to do the pharmacokinetic study with the product that will be used for surgery because patients can respond quite differently to different products.

It is important to continue to maintain adequate factor IX levels to minimize bleeding after surgery, while the patient heals. Excessive bleeding internally at the surgical site can interfere with proper healing and affect the long-term outcome of the procedure. For instance, with a total joint replacement, excessive bleeding could cause the body to try to reject the implanted artificial joint. This sometimes happens by the body growing a tough fibrous material around the implant to try to wall it off from the neighboring tissue. The fibrous material can interfere with the proper functioning of the artificial joint. In other types of surgery, excessive post-surgical bleeding can cause excessive scar tissue to form, which could interfere with proper functioning in what-ever part of the body is involved. None of this should discourage the hemophilia B patient from considering surgery when needed. All of these issues have relatively simple solutions today. Physicians and surgeons have performed a large number of surgeries on hemophilia patients with success in the vast majority of cases. The patient and his family should discuss the risks and benefits for his individual case with his physician in order to make an informed, confident decision about surgery.~

---

Prophylaxis Update

Dr. David Clark

Prophylaxis or prophylactic treatment is considered to be the best method of treatment for hemophilia B. Prophylaxis, when started at an early age, is the only known treatment that can prevent the joint deterioration that is a major consequence of hemophilia and the major hindrance to quality of life for the hemophilia patient. Prophylaxis is regular administration of clotting factor, often two or three times a week, with the aim of keeping the blood level of factor IX high enough to prevent bleeding into the joints.However, even though prophylaxis is considered to be the best treatment, the best method for performing prophylaxis is still in question. Physicians and researchers are still trying to find the optimum dose and frequency of infusion to give the best results. A recent study from the hemophilia treatment center in Malmo, Sweden, one of the pioneers in developing prophylactic treatment, now shows that there may be no single method that works for all patients. The best results are probably obtained by tailoring the dose and frequency to each patient based on their individual results.

The Malmo group followed a large number of Hemophilia A and B patients on prophylaxis for six years and found some interesting results. They looked at how various treatment regimens (dose and frequency of infusion) affected factor levels in the blood and how the factor level in the blood affected the incidence of bleeding. They looked at the effects of age and level of existing joint damage. One goal was to determine whether the amount of existing joint damage affected the factor level needed to prevent new joint bleeds and further damage.

The study of the distribution of any drug in the body is called pharmacokinetics. (“Pharmaco”) refers to drugs, as in “pharmaceuticals”, and “kinetics” is movement, so pharmacokinetics is the study of the movement of drugs throughout the body. When factor IX is injected into a vein, it quickly distributes itself throughout the bloodstream. If you were measuring the amount of factor IX in the blood, you would see an immediate sharp increase in the factor IX level. Then the factor IX level starts to fall off. Some of it is used up in clotting and some of it naturally degrades and is removed by the body. When the next infusion is given, the level jumps up again and then falls off, repeating the process. In prophylaxis, the factor IX level over time looks like a sawtooth pattern with peaks and valleys; the lowest point, the valleys, are called the
trough levels. The main goal in prophylaxis is to keep the trough levels high enough to minimize bleeding into the joints and joint damage. Besides the trough level, the two main pharaco-kinetic parameters are the recovery and half-life. For factor IX, the recovery is the amount of factor IX that can be found in the blood immediately
after infusion. Interestingly, the average recovery for factor IX is only 50%, that is, only about half of the factor IX infused shows up in the blood. The rest of the factor IX immediately goes to other parts of the body. The half-life is a measure of how long the factor IX stays in the bloodstream; it is the amount of time it takes for half of the factor IX to disappear (not including the half that never shows up in the first place because of the 50% recovery). Note that physicians also use a number of other parameters as indicators of pharmacokinetics, but all of those parameters are related to the recovery and half-life.

This study reinforced the findings of other studies that the pharmacokinetics of clotting factors varies widely from patient to patient. Therefore, it is best to tailor the dose and frequency to the individual patient. Although it is expensive and time-consuming to do a pharmacokinetic study on each patient, it is probably worthwhile in the long run.
It can even pay for itself if it is found, for instance, that a patient has a higher recovery or longer half-life. Then that patient might need lower or less frequent doses and thus use less factor concentrate. Conversely, a patient with a lower recovery or shorter half-life might need larger or more frequent doses to be treated effectively.

It has been known for a long time that patients with moderate hemophilia, who have more than 1/% of normal factor levels in their blood, bleed only infrequently and rarely experience severe joint damage. Therefore, one of the main ideas behind prophylaxis has been that if you change severe hemophilia into moderate hemophilia by keeping the trough levels above 1%, you will generally prevent joint damage. The most interesting findings of the Malmo study was that the amount of factor IX in the bloodstream is not strongly related to the reduction in joint bleeding.
The study found patients who experienced no bleeding problems even when their factor levels were below 1% and others who still experienced bleeds even with levels above 3%. They also did not find any relationship between the amount of existing joint damage and the amount of factor IX needed to prevent new bleeds. Therefore, not only does the pharmacokinetics vary from patient to patient, but each patient may require a different trough level for optimum effectiveness of the treatment.

The bottom line is that prophylactic dosing should be tailored to the individual and should be based on clinical outcome, that is, actual reduction in bleeding, not just on measured blood levels of factor IX. Rather than the ideal of having a single dosage that works for everyone, the patient and physician need to work together to determine the patient’s pharmacokinetic profile and his required trough level. That requires more work up front, but should give better results over the long run. ~

---

Grifols Donates 1.4 Million

In Hemophilia Blood Clotting Therapies to World Federation of Hemophilia

As part of its ongoing commitment to the global disorders community, Grifols has donated plasma-derived blood clotting therapies to be used to treat patients in developing countries. The donated products include those used to treat both hemophilia A and B and will be targeted for patients in developing countries where access to adequate treatment is often lacking. It is anticipated that the donation of hemophilia therapies will be used to treat hundreds of patients. The WFH will direct the distribution of the donated products to areas of greatest need.

An estimated 400,000 people around the world have hemophilia, yet, only 25% received adequate
treatment. According to WFH President, Mark Skinner their new vision is “Treatment for all”.
Mr. Skinner added “The Grifols donation moves us up one step closer to making our vision a reality; but we have a long way to go.”
“Through the donation we hope our therapies will reach the most needy patients. The mission of WFH is noble, and is consistent with the ethical value of our company.” said Victor Grifols, President and CEO of the company.

---

Thank you all for your participation in our Survey. The results are attached with the newsletter.

The information really helps us to continue to provide you with the quality of information that you would like to see in upcoming newsletters. We hear you and we hope you find the information useful as well.

---

We hope to see you at the NHF Conference in Philadelphia!

Reminder: SAVE THE DATE:

October 12-14, 2006

---

For back issues of Factor Nine Newsletter or for more information on research please call or write to:
Kim Phelan, 225 West 34th Street, Suite 710, New York, New York 10122, Telephone (212) 554-6898
Telefax (212) 554-6906, E-mail: hemob@ix.netcom.com Website: coalitonforhemophilia.org