Overview of Topics Information about Hemophilia Information about ADVATE Patient FAQ    
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What is ADVATE [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method]?

ADVATE is the newest member of the Shire family of hemophilia A therapies. Through its plasma/albumin-free processing, ADVATE eliminates the risk of transmission of viruses and infectious agents that may be associated with blood components, including plasma. ADVATE is the only full-length factor VIII available that has no blood based additives at all stages of processing.1

Why was ADVATE developed?

ADVATE was developed in response to the hemophilia community’s desire for safe therapies. The hemophilia community is especially vulnerable to blood-borne diseases because of its dependence on clotting factors which used to be purified from blood. Up until now, even recombinant factor VIII therapies contain at least trace amounts of blood additives.2,3 With the impact of Human Immunodeficiency Virus (HIV) and Hepatitis C (HCV) on the hemophilia community in the 1980s to early 1990s and the emergence of a number of infectious agents such as West Nile Virus (WNV) and variant Creutzfeldt-Jakob Disease (vCJD), the hemophilia community emphasized more than ever the importance of having safe products. Current screening and inactivation techniques have greatly improved blood safety, but cannot completely remove the risk that may be associated with pathogen transmission from plasma protein additives used in many recombinant factor VIII therapies.4 As a result, a number of policies were established around the world; one of which was the Policy of Blood, Blood Products and Alternatives issued by the Canadian Hemophilia Society in 2002. It stated that:

“The elimination of animal and human proteins as stabilizers in the final formulation, or as nutrients in the cell culture, or in any other part of the process, should be considered as a goal in terms of the quality of products.”5

Shire’s response to this challenge was to develop the first factor VIII in the world that does not add any plasma proteins in any stage of processing.1 The significance of this development is that ADVATE eliminates blood-borne pathogen risk that may be associated with blood additives.

How is ADVATE different from other recombinant factor VIII therapies?

All other factor VIII therapies use blood additives (such as albumin) at some point in their processing.3 Despite purification, trace amounts of these blood components can remain all the way through to the final product.3 As a result, there is still a potential risk for blood-borne viruses and infectious agents associated with such additives. ADVATE is the first and only recombinant factor VIII therapy that does not use these additives at any point in its processing, thereby eliminating the associated risk.

Why is plasma and albumin free processing important?

New infectious agents continue to emerge. One example is variant Creutzfeldt-Jakob Disease (vCJD). Some of these emerging pathogens may have the potential to be transmitted through blood and blood protein additives. All other recombinant factor VIII products use blood protein additives in some stage of their processing. These products are considered safe with regard to known infectious agents. Nonetheless, concerns regarding the risk of blood-borne viruses and infectious agents may remain. In addition, most safety measures have been introduced after a pathogen had been identified and understood. This approach is largely reactive. Since ADVATE does not use any blood protein additives in its processing, it is the only therapy that proactively reduces such associated risk before transmission can happen.1

Does ADVATE have any side effects?

As with all recombinant factor VIII therapies, there are possible side effects that may be associated with ADVATE; however, clinical studies have shown that ADVATE has been well received and well tolerated in all age groups.1 The most common related side effects observed during the ADVATE clinical studies include strange taste in mouth, headache, dizziness and flushing.6

The formation of inhibitors has been observed with all factor VIII therapies, including ADVATE. Contact your doctor if you are not able to prevent or control bleeding episodes with your regular doses of prescribed factor VIII therapy.

Allergic reaction to ADVATE is possible although rare. Symptoms of an allergic reaction may include rash, hives, itching, tightness in throat or chest, difficulty breathing or feeling dizzy, light-headed or weak pulse. If you experience any of these symptoms, stop the infusion immediately and promptly contact your doctor. Let your doctor know if you have had any previous allergic reactions to other factor VIII therapies.

I haven’t had any problems with inhibitors in the past. Should I be concerned about using ADVATE?

Inhibitor formation is always a possibility whenever you introduce a protein of any kind into your body. It is a complex issue and may have multiple contributing factors. Scientific data indicates that a therapy change causing inhibitor development is rare in previously treated patients with more than 50 exposure days whether or not they have had a history of inhibitors.7 In several ADVATE clinical studies, only 1 in more than 200 previously treated patients (PTPs)* who had completed the studies developed an inhibitor which was low-titre, non-persistent and asymptomatic.1

* PTPs with documented greater than 50 exposure days history to any FVIII therapy
 

What has been the experience of ADVATE in other countries where it has received approval?

ADVATE has been used in the US since mid-2003 and Europe since early 2004. More than 3 billion units of ADVATE have been distributed to patients of all age groups worldwide as of October 2007.8

There are many factor VIII therapies available. How do I know which one is right for me?

The easiest way to find out if ADVATE is the right treatment for you is to make an appointment with your physician. Ask questions. After reviewing your records, you and your doctor can best decide if ADVATE is right for you.

How do I administer ADVATE?

Your doctor will tell you how much ADVATE you should take. ADVATE is dosed similarly to RECOMBINATE, requiring a comparable amount of factor to increase your blood factor levels.

For your convenience, each vial is marked with peel-off labels to keep track of how much ADVATE you’ve taken and when.

ADVATE is available in single-dose vials in four convenient sizes of 250 (Low), 500 (Medium), 1000 (High), 1500 IU (Super High) and 2000 IU (Ultra-High) per vial potencies. So you choose the vial size of factor VIII you need, according to your doctor’s guidance. These potencies are also colour coded for immediate identification; thus, reducing the likelihood of confusion. ADVATE is also packaged with 5mL of Sterile Water for Injection, BAXJECT II needleless transfer device, butterfly needle, alcohol swab, adhesive bandages and 10mL sterile syringe. A description of how to use ADVATE is conveniently outlined in an easy-to-read patient insert.1

Instructions for use of the Baxject II needleless transfer device are included in the patient insert and also on the internet at http://www.baxject2.com/ca_home.html.

How do I store ADVATE?

ADVATE should be stored refrigerated, however, it may be stored at room temperature for up to 6 months or until expiration date, whichever comes first.1 ADVATE is now packaged in two cartons. The smaller product carton is designed to separate from the ancillary carton, allowing patients to store only the product carton in the refrigerator. For more information on storage recommendations please refer to the Patient Package Insert.

Is there enough ADVATE to go around?

Shire has been dedicated to increasing supply of its recombinant therapies since 1992. Each year since then, we have steadily increased the amount of product produced and available for patients. We are equally committed to bringing a secure supply of ADVATE to the market and to developing safe products.

Our newest processing facility, located in Neuchâtel, Switzerland, is a state-of-the-art facility. This facility has the capacity to ensure supplies of ADVATE based on current and anticipated future needs.

For more information please call 1.800.387.8399.

Glossary of Terms 9, 10


Albumin: Albumin is the most prevalent protein found in blood. It is used as a stabilizer in the manufacturing process of several factor VIII therapies. Albumin is also used in the manufacture or formulation of some recombinant factor VIII products.

Antibody: A protein produced by blood plasma cells that binds specifically to substances that the body recognizes as foreign. Once bound, the antibody can lead to the destruction or inactivation of the foreign substance. Inhibitors are antibodies that occur in response to replacement therapies for hemophilia, factor VIII or factor IX.

Antihemophilic Factor (AHF): Another term for factor VIII, which is one of the clotting factors in the blood needed to form fibrin, which in turn helps stop bleeding. Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method (rAHF-PFM) factor VIII that is derived from a non-human plasma source in a laboratory without the addition of human or animal proteins in any stage of its processing. (see Recombinant Factor).

Blood-borne Pathogen: A microscopic agent found in blood that may cause disease. Pathogens can be viruses, bacteria or prions.

Clot (blood clot): A plug that forms at the wound site to stop the body from bleeding.

Clotting factor: Proteins that are needed to make blood clots.

Coagulation: Another word for clotting of the blood. Coagulation is the process in which liquid blood is changed into a jelly-like substance to seal or plug an injured blood vessel. People with hemophilia have decreased levels of a functional protein in their blood that is necessary to create an effective blood clot.

Factor VIII (FVIII): One of the clotting proteins that speeds up the process to efficiently create a fibrin net.

Factor IX (FIX): One of the clotting proteins that speeds up the process to efficiently create a fibrin net.

Fibrin: A protein that helps platelets bind to a wound site to form a firm blood clot.

Hemophilia: Hemophilia is a genetic bleeding disorder that prevents blood from forming an effective clot. Without effective blood clotting, internal injuries and large external lacerations cannot heal properly. There are two types of hemophilia. Hemophilia A (also called Classic Hemophilia) is the condition where clotting factor VIII is either absent or not present in sufficient amounts. There are approximately 2000 Hemophilia A patients in Canada. Approximately 450 patients in Canada have Hemophilia B (also called Christmas Disease) who lack or produce insufficient amounts of factor IX.

Infusion: Injecting medication directly into a vein.

Inhibitors: Sometimes the body’s immune system mistakes infused factor for a foreign substance, so it creates antibodies that destroy the factor, which prevents rapid clotting. When the body creates these antibodies, the person is said to have an inhibitor.

Pathogens: Any virus, microorganism, or other substance causing disease.

Plasma: Liquid component of blood where the clotting factors are found.

Plasma Protein: Any proteins found in the liquid component of the blood.

Platelets: Small cell fragments in the blood that attach to damaged blood vessels and facilitate clotting.

Prions: A microscopic piece of protein that is similar to a virus but even smaller, and does not have any genetic material. Prions cause mad cow disease and Creutzfeldt-Jacob disease (vCJD), and other degenerative brain disorders.

Protein: Any of a large group of tiny substances that form the building blocks of all living things. Proteins exist in all animal and vegetable matter and are necessary for cell growth and repair.

Recombinant Factor: Recombinant factor is factor VIIa, factor VIII, or factor IX concentrate created in a laboratory. These factor concentrates are not derived from human blood or plasma. Using recombinant DNA technology, the human factor gene is put into a non-human cell, giving it the ability to produce human clotting factors. Although recombinant factor concentrates are not made from human plasma, the factor they produce is human factor. Recombinant and plasma-derived factors are nearly identical in their physical and chemical structures, and both concentrates are made according to the genetic instructions contained within the human clotting factor gene. They also behave the same once infused into the body.

Recombinant Factor VIII (rFVIII): Factor VIII that is produced by a genetically engineered mammalian cell line rather than isolated from plasma. The Chinese hamster ovary (CHO) cell line is one of the most common cell lines used to produce recombinant therapeutic proteins.

Replacement therapy: In hemophilia, the infusion of clotting factor(s) to serve as a temporary substitute for the body’s missing or flawed factor. In hemophilia A, factor VIII is infused as the replacement therapy.

Virus: Tiny pieces of genetic material and proteins that can cause infection and disease. Requiring a host to reproduce, viruses are typically not considered living organisms. By their nature, viruses mutate and evolve.

References

1. ADVATE, Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method Product Monograph. Mississauga, ON: Baxter Corporation; 2006.
2. The National Hemophilia Foundation. MASAC Recommendations Concerning The Treatment of Hemophilia and other Bleeding Disorders. MASAC Document #151. November 2003.
3. Kogenate FS. Bayer Corporation. European Public Assessment Report. October 2003.
4. Data on file. Westlake Village, Calif: Baxter Healthcare Corporation.
5. The Canadian Hemophilia Society. CHS Policy on Blood, Blood Products and their Alternatives. November 2002.
6. Tarantino MD et al. Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A. Haemophilia (2004), 10, 428-437.
7. Scharrer I et al. Lack of evidence for increased inhibitor incidence in patients switched from plasma-derived to recombinant factor VIII. Haemophilia. 2001; 7: 346-348.
8. Data on file. Westlake Village, Calif: Baxter Healthcare Corporation.
9. Hemophilia Galaxy website: Encyclopedia section. Available at: www.hemophiliagalaxy.com. Accessed December 6, 2004.
10. Stedman’s Medical Dictionary. 25th Edition. 1990.