Baxter Submits Application for FDA Approval of FEIBA NF for Prophylactic Use in Hemophilia A and B Patients with Inhibitors

DEERFIELD, Ill.--(BUSINESS WIRE)--
Baxter International Inc. (NYSE:BAX) today announced that the company
has submitted a biologics license application (BLA) supplement to the
U.S. Food and Drug Administration (FDA) for the approval of prophylaxis
treatment of FEIBA NF [Anti-Inhibitor Coagulant Complex], Nanofiltered
and Vapor Heated, in patients with hemophilia A or B and inhibitors.

As many as one third of people with hemophilia develop an inhibitor to
factor replacement used to treat or prevent bleeding episodes. The
presence of an inhibitor makes response to treatment more challenging,
and patients with inhibitors have an increased risk of developing
complications such as joint damage. It is estimated that approximately
17,000 people in the U.S. have been diagnosed with hemophilia A or B.

''This regulatory submission helps fulfill Baxter’s commitment to
advancing care for patients who have developed inhibitors, a serious and
sometimes life-threatening complication for those with hemophilia A or
B,'' said Prof. Hartmut J. Ehrlich, M.D., vice president of global
research and development in Baxter’s BioScience business. ''Baxter has
been supporting innovations in care for the hemophilia community for
more than 60 years, and our work continues not only with FEIBA, but also
with other treatments we are actively developing.''

Baxter recently shared top-line results from the pivotal Phase III study
that formed the basis for the BLA submission. Results from the study
demonstrated that routine prophylactic treatment with FEIBA NF reduced
median annual bleed rate (ABR) from 28.7 during FEIBA NF on-demand
treatment compared to 7.9 during FEIBA NF prophylactic treatment (a
72.5% reduction), with 17 percent (3 of 17) of patients in the
intent-to-treat group experiencing zero joint bleeds. The complete
results of the Phase III study will be presented at a scientific meeting
later this year.

The prospective, open label, randomized, multi-center, parallel study
investigated the efficacy, safety and health-related quality of life
benefits of FEIBA NF prophylactic treatment compared to on-demand
treatment in 36 patients with hemophilia A or B and inhibitors over a
12-month period. The most commonly reported adverse reactions in the
study were hypersensitivity, dizziness, headache, rash, hypotension and
hepatitis B surface antibody positive laboratory test result. The
occurrence of hepatitis B surface antibodies has been seen in other
plasma-derived products and could be due to the passive transfer of
antibodies following FEIBA NF treatment. None of the subjects showed any
signs or symptoms of hepatitis B infection.

FEIBA NF is not indicated for prophylaxis use in the United States.
Canada, The Netherlands, Israel, Australia/New Zealand, Japan and South
Korea also do not have a prophylaxis indication.

In the U.S., FEIBA NF [Anti-Inhibitor Coagulant Complex] is indicated
for the control of spontaneous bleeding episodes or to cover surgical
interventions in hemophilia A and hemophilia B patients with inhibitors.

Clinical experience suggests that patients with a Factor VIII inhibitor
titer of less than five Bethesda Units (B.U.) may be successfully
treated with Antihemophilic Factor. Patients with titers ranging between
five and ten B.U. may either be treated with Antihemophilic Factor or
FEIBA NF. Cases with Factor VIII inhibitor titers greater than 10 B.U.
have generally been refractory to treatment with Antihemophilic Factor.

Inadequate response to treatment may result from an abnormal platelet
count or impaired platelet function that were present before treatment
with FEIBA NF, nanofiltered and vapor-heated.

The use of FEIBA NF is contraindicated:

At first sign or symptoms of an infusion/hypersensitivity reaction or a
thrombotic/ thromboembolic event, FEIBA NF administration should be
stopped immediately and diagnostic and therapeutic measures initiated as
appropriate.

Allergic-type hypersensitivity reactions, including severe anaphylactoid
reactions, have been reported following the infusion of FEIBA. The
symptoms include urticaria, angioedema, gastrointestinal manifestations,
bronchospasm, and hypotension; these reactions can be severe and can be
systemic.

Many of the reported cases of thromboembolic events occurred with doses
above 200 units/kg/day or in patients with other risk factors.

Infusion of FEIBA NF should not exceed single dosage of 100 U/kg and
daily doses of 200 U/kg of body weight. Patients receiving more than 100
U/kg of FEIBA NF must be monitored for the development of DIC and/or
symptoms of acute coronary ischemia. High doses of FEIBA NF should be
given only as long as absolutely necessary to stop bleeding.

FEIBA NF should be used with particular caution and only if there are no
therapeutic alternatives in patients at risk of DIC, arterial or venous
thrombosis.

If clinical signs of intravascular coagulation occur, which include
changes in blood pressure, changes in pulse rate, respiratory distress,
chest pain and/or cough, infusion of FEIBA NF should be stopped promptly.

Non-hemophilic patients with acquired inhibitors against factors VIII,
IX or XII may have both a bleeding tendency and an increased risk of
thrombosis at the same time.

FEIBA NF is made from human plasma and may carry a risk of transmitting
infectious agents, e.g., viruses and theoretically, the variant
Creutzfeldt-Jakob disease (vCJD) agent.

Adverse reactions reported in clinical studies with FEIBA were
anamnestic response, somnolence, dizziness, dysgeusia, dyspnea,
hypoesthesia, nausea, chills, pyrexia, chest pain and chest discomfort.

For information on FEIBA NF use in the United States, please visit: http://www.baxter.com/healthcare_professionals/products/feiba_nf.html.

Licenses and licensing conditions may vary from country to country;
therefore please always consult your local full prescribing information.
Please check the FEIBA NF website for information on indications
approved in other countries.

Hemophilia is a rare genetic blood clotting disorder that primarily
affects males. People living with hemophilia do not have
enough of, or are missing, one of the blood clotting proteins naturally
found in blood. Two of the most common forms of hemophilia are A and B.
In people with hemophilia A, clotting factor VIII is not present in
sufficient amounts or is absent. Without enough FVIII,
people with hemophilia can experience spontaneous, uncontrolled internal
bleeding that is painful, debilitating, damaging to joints and
potentially fatal. According to the World Federation of
Hemophilia, it is estimated that more than 400,000 people in the world
have hemophilia. All races and economic groups are affected
equally.

Hemophilia B is the second most common type of hemophilia (also known as
Christmas disease) and is the result of insufficient amounts of clotting
factor IX, a naturally occurring protein in blood that controls bleeding.
Approximately 26,000 people worldwide, including more than 4,000 in the
U.S., have been diagnosed with hemophilia B. Hemophilia B is
often a debilitating, chronic disease with complications that include
bleeding episodes, hemophilic arthropathy (bleeding into a joint) and
hospitalization.

As many as one-third of patients with severe or moderately severe
hemophilia A are at risk for developing inhibitors, which are antibodies
produced by the body’s immune system in response to factor replacement
therapy. Inhibitors cause the body to work against the factor
replacement therapy, neutralizing its effect and preventing an
individual’s blood from clotting. Individuals who have
inhibitors have a form of hemophilia that is more difficult to control,
with an increased risk of uncontrolled bleeding, compared to patients
without inhibitors. Inhibitor development is considered one of the most
serious complications associated with hemophilia treatment, and may
include other associated complications such as impaired movement,
increased need for surgery and greater complexity or risk associated
with surgery.

Baxter has more than 60 years of experience in hemophilia and has
introduced a number of therapeutic firsts for hemophilia patients.
Baxter has the broadest portfolio of hemophilia treatments in the
industry and is able to meet individual therapy choices, providing a
range of options at each treatment stage. The company’s work is focused
on optimizing hemophilia care and improving the lives of people living
with hemophilia A and B worldwide.

Baxter International Inc., through its subsidiaries, develops,
manufactures and markets products that save and sustain the lives of
people with hemophilia, immune disorders, cancer, infectious diseases,
kidney disease, trauma and other chronic and acute medical conditions.
As a global, diversified healthcare company, Baxter applies a unique
combination of expertise in medical devices, pharmaceuticals and
biotechnology to create products that advance patient care worldwide.

World Federation of Hemophilia Report on the Annual Global
Survey 2011. World Federation of Hemophilia. Accessed on February 19,
2013. Available at: http://www1.wfh.org/publications/files/pdf-1488.pdf

About Bleeding Disorders: Treatment. World Federation of
Hemophilia. Accessed on: February 19, 2013. Available at: http://www.wfh.org/en/page.aspx?pid=642

Frequently Asked Questions About Hemophilia. World
Federation of Hemophilia. Accessed on: January 29, 2013. Available at: http://www.wfh.org/en/page.aspx?pid=637

Frequently Asked Questions About Hemophilia. World
Federation of Hemophilia. Accessed on January 29, 2013 Available at: http://www.wfh.org/en/page.aspx?pid=637

World Federation of Hemophilia Report on the Annual Global
Survey 2011. World Federation of Hemophilia. Accessed on February 19,
2013. Available at: http://www1.wfh.org/publications/files/pdf-1488.pdf

Lee, C. A. (2011) Hemophilia Care in the Modern World, in
Current and Future Issues in Hemophilia Care (eds E.-C.
Rodríguez-Merchán and L. A. Valentino), Wiley-Blackwell, Oxford, UK.
Accessed on January 29, 2013. Screen shot of page available here

What are Inhibitors (section)?. World Federation of
Hemophilia. Accessed on January 29, 2013. Available at: http://www.wfh.org/en/page.aspx?pid=651.

Leissinger, Cindy A. Prevention of Bleeds in Hemophilia
Patients With Inhibitors: Emerging Data and Clinical Direction. . 2004; 77:187-193.

Baxter International Inc.Brian Kyhos,
(224) 948-4210Deborah Spak, (224) 948-2349orMary Kay Ladone, (224) 948-3371Clare Trachtman,
(224) 948-3085

Source: Baxter International Inc.