INHIBITORS TO CLOTTING FACTOR THERAPY ARE SIGNIFICANTLY IMPACTING THE LIVES OF MANY PEOPLE (MOST OF THEM CHILDREN) WITH HEMOPHILIA.  

* THERE HAS BEEN LITTLE OR NO PROGRESS IN REDUCING THE RATE OF INHIBITOR DEVELOPMENT. 

* RECENT STUDIES ARE INDICATING THAT THE RATE OF INHIBITOR DEVELOPMENT TO THESE PRODUCTS ARE HIGHER THAN PREVIOUSLY THOUGHT.

* THERE IS MUCH DEBATE AS TO WHETHER SOME PRODUCTS MAY CAUSE MORE INHIBITORS THAN OTHERS.  

* CURRENT LICENSING REQUIREMENTS FOR CLOTTING FACTOR MEDICATIONS ARE NOT SUFFICIENT  TO REPORT AND CONSIDER THE DEVELOPMENT OF AN INHIBITOR AS A SAFETY AND EFFECTIVENESS CONCERN.

* WE CANNOT MAKE INFORMED DECISIONS ABOUT THE USE OF THESE PRODUCTS WITHOUT COMPLETE INFORMATION.  

PLEASE HELP US BY ASKING THAT ALL CLOTTING FACTOR THERAPIES BE TESTED AND MONITORED FOR INHIBITORS IN PREVIOUSLY UNTREATED PATIENTS.     

People with hemophilia depend on clotting factor replacement therapies to control bleeding and manage their disorder.  Hemophilia is a life long disorder and replacement therapy must be continued through out a person's life to manage bleeding.  Some people with hemophilia develop neutralizing antibodies "called inhibitors" to the clotting factor medications which makes it difficult or impossible for these individuals to use clotting factor replacement to manage or prevent bleeding.  The development of an inhibitor increases morbidity and mortality of people with hemophilia, significantly increases the cost of treatment, and reduces the overall quality of life for these people and their families.  

Most inhibitors occur in very young children, who are just beginning therapy and have received less than 50 days of replacement therapy. Patients who have received less than 50 days of therapy are referred to as Previously Untreated Patients or PUPs.   Recent studies have shown that inhibitors develop overall in about 30% of PUPs with severe hemophilia A. Inhibitor rates in Hemophilia B PUPs are thought to be less (around 10%) but can have more severe consequences due to the association of severe allergic reactions that coincide with inhibitor development in many of these children.  Inhibitors rates in mild and moderate hemophilia A and B may approximate that seen in severely affected individuals but may not be detected until later in life due to the more infrequent treatment required in these individuals.  

Most people with hemophilia in developed countries today receive clotting factor replacement therapy by using biologic medications that have been synthesized (recombinant therapies) to mimic naturally occurring proteins or plasma derived products that have been precipitated, processed and sanitized from whole blood donations (plasma derived).  These products are licensed and distributed as biologic medications by different companies around the world. Regulatory agencies in various countries determine which products are safe and effective enough to be licensed for use by people with hemophilia. The World Federation of Hemophilia (WFH), the International Society on Thrombosis and Haemostatis (ISTH), and hemophilia organizations within various countries - like the National Hemophilia Foundation (NHF) and the Hemophilia Federation of America (HFA) -  work with government regulators to determine the safety standards for these products.  

Current standards followed by licensing agencies around the world have determined that the development of an inhibitor to a clotting factor replacement product, when it occurs in  someone who is considered a Previously Untreated Patients (PUP), is NOT  product related and therefore is NOT a safety concern and should NOT be reported and measured as a condition of license of these medications.  Licensing authorities have accepted that only  Previously Treated Patients (PTPs) who have received more than 50 to 120 doses of clotting factor therapy should be used to test a clotting factor therapy for licensure.  Only inhibitors that occur in Previously Treated Patients (PTPs) are considered significant to determine the safety of a clotting factor medication. Additionally, there is no requirement that companies who manufacture these clotting factor medications test these products in PUPs and even if they do, the companies are not required to report the rates of inhibitors that develop in PUPs when they use these products. In fact, current product labeling and packaging inserts do not require the disclosure of any inhibitor rates in PUPs.  There is also no national or international surveillance system required to monitor the rate of inhibitor development in the products.

As people with hemophilia who depend on the use of these clotting factor medications for survival, we are very concerned with inhibitors.  Many of us know first hand how tragic and life altering the development of an inhibitor can be to us and to our children.  There are many children and adults living with hemophilia today who have developed inhibitors to all the current clotting factor replacement therapies and must rely on substandard "bypassing" therapies to manage bleeding.  Parents of young children who will need to begin clotting factor therapy are concerned about the high rate of inhibitor development that has been shown with these products.  Because most inhibitors do develop in young children and people who have had little exposure to these products we believe that inhibitors in PUPs should be considered a product safety concern.  Patients who have successfully used clotting factor therapies (PTPs)  without the development of an inhibitor have already demonstrated tolerance to clotting factor therapies and  therefore do not provide a complete enough profile to be used for the measurement of a products safety and effectiveness.  We believe it is imperative to include individuals who have not been previously exposed to clotting factor replacement therapies (PUPs) to truly determine a products safety and effectiveness.

We are signing this petition to ask the World Federation of Hemophilia, the International Society on Thrombosis and Haemostasis, the National Hemophilia Foundation and the Hemophilia Federation of America, to ask regulating authorities who license and oversee the manufacture of clotting factor replacement therapies around the world to consider the development of an inhibitor in a Previously Untreated Patient to be considered a safety concern and a serious adverse event directly associated with the use of a clotting factor replacement product. We request that inhibitors detected in Previously Untreated Patients during the licensure or post licensure of these products be considered in the products licensure requirements.  

In order for people with hemophilia or parents or caregivers of children with hemophilia to make informed decisions about clotting factor replacement therapy, we need to know about all the product safety outcomes of each individual product so that we may make informed decisions about the risks and benefit of any particular therapy we may be considering.  We consider the rate of inhibitor development to these products in Previously Untreated Patients to be a primary safety measure and something we must consider when we begin therapy with these products.  Therefore, we also request that inhibitors in PUPs be included in clinical trial and post licensure follow up studies of these products.  We also request that all inhibitors detected in PUPs and known to the companies manufacturing these products be disclosed and reported in the products labeling.  

Please help us begin to address the significant complication of inhibitors in hemophilia treatment.  Every day, more and more people with hemophilia are developing inhibitors to these clotting factor medications.  Many of them are young children who are just beginning therapy.  Once an inhibitor develops, the course of hemophilia and the impact it has on a person's life is significantly changed for the worse. As patients and caregivers we need as much information as possible about inhibitors to help us make informed choices for treatment.