Baxter Announces Phase III Data Evaluating Prophylaxis Treatment of FEIBA NF for Hemophilia Patients with Inhibitors
Pivotal study to form basis for upcoming biologic license application to the U.S. FDA
DEERFIELD, Ill., JANUARY 8, 2013 - Baxter International Inc. (NYSE:BAX) today announced pivotal Phase III study results evaluating the efficacy and safety of routine prophylaxis compared to on-demand treatment of FEIBA NF [Anti-Inhibitor Coagulant Complex], Nanofiltered and Vapor Heated, in patients with hemophilia A or B and inhibitors. Top-line results from the study showed a reduced median annual bleed rate (ABR) from 28.7 during FEIBA NF on-demand treatment to 7.9 during FEIBA NF prophylactic treatment (a 72.5% reduction). The Phase III study will form the basis of a biologics license application (BLA) to be filed with the U.S. Food and Drug Administration (FDA) in the first quarter of 2013.
As many as one-third of people with hemophilia develop an inhibitor to a product 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.
"Treatment with FEIBA NF resulted in a significant reduction in annual bleed rate (ABR) of all types of bleeds in the prophylaxis arm as compared to the on-demand arm," said lead investigator, Dr. Sandra Antunes MD, UNIFESP, Sao Paulo, Brazil. "Three of the 17 intent to treat patients (17.6 %) in the prophylaxis arm did not experience any bleeding episodes during the study, and this is very significant for hemophilia patients with inhibitors."
The Phase III 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 a transitory increase in hepatitis B surface antibodies has been seen in certain plasma-derived products and could be attributed to the passive transfer of antibodies following FEIBA NF treatment. None of the subjects showed any signs or symptoms of hepatitis B infection.
This latest study adds to the clinical evidence supporting the prophylactic use of FEIBA, building on an investigator initiated study showing that FEIBA can reduce bleeding events in patients with severe hemophilia A and inhibitors when compared to on-demand treatment (results published in The New England Journal of Medicine in November 2011).
"One of the greatest remaining challenges in the management of hemophilia is the development of inhibitors, which can lead to more difficult-to-control and sometimes life-threatening bleeding. The FEIBA NF prophylaxis study demonstrates Baxter's dedication to providing treatment options to the hemophilia community, including effective inhibitor management," said Prof. Hartmut J. Ehrlich, M.D., vice president of global research and development in Baxter's BioScience business.
About FEIBA NF
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.
Indications for FEIBA NF
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 5 and 10 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.
Detailed Important Risk Information for FEIBA NF
Thrombotic and thromboembolic events have been reported during postmarketing surveillance following infusion of FEIBA VH or FEIBA NF, particularly following the administration of high doses and/or in patients with thrombotic risk factors.
The use of FEIBA NF is contraindicated:
- In patients who have known anaphylactic or severe hypersensitivity reactions to the product.
- In patients who are known to have a normal coagulation mechanism.
- For the treatment of bleeding episodes resulting from coagulation factor. deficiencies in the absence of inhibitors to coagulation factor VIII or coagulation factor IX.
- In patients with significant signs of disseminated intravascular coagulation (DIC).
- In patients with acute thrombosis or embolism (including myocardial infarction).
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 VH or 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. It may carry a risk of transmitting infectious agents, e.g., viruses and theoretically, the Creutzfeldt-Jakob disease (CJD) 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.
Please see full prescribing information for FEIBA NF at:
Licenses and licensing conditions may vary from country to country; therefore please always consult your local full prescribing information. Please check FEIBA NF website for information on indications approved in other countries.
About Hemophilia A
Hemophilia is a rare genetic blood clotting disorder that primarily affects males.1 People living with hemophilia do not have enough of, or are missing, one of the blood clotting proteins naturally found in blood.1 Two of the most common forms of hemophilia are A and B.2 In people with hemophilia A, clotting factor VIII is not present in sufficient amounts or is absent.2 Without enough FVIII, people with hemophilia can experience spontaneous, uncontrolled internal bleeding that is painful, debilitating, damaging to joints and potentially fatal.2 According to the World Federation of Hemophilia, more than 400,000 people in the world have hemophilia.2 All races and economic groups are affected equally.1
About Hemophilia B
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.3 Approximately 25,000 people worldwide, including more than 4,000 in the U.S., have been diagnosed with hemophilia B.4 Hemophilia B is often a debilitating, chronic disease with complications that include bleeding episodes, hemophilic arthropathy (bleeding into a joint) and hospitalization.5
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 appropriate clotting.6 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, lower life expectancy and poor health-related quality of life.6,7
About Baxter in Hemophilia
Baxter has more than 60 years 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.
About Baxter International Inc.
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.
This release includes forward-looking statements concerning the company's Phase III study evaluating the efficacy and safety of routine prophylaxis compared to on-demand treatment of FEIBA NF in hemophilia patients with inhibitors, including expectations regarding related regulatory filings. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; product quality or patient safety issues; and other risks identified in Baxter's most recent filing on Form 10-K and other SEC filings, all of which are available on Baxter's website. Baxter does not undertake to update its forward-looking statements.
1What is Hemophilia? World Federation of Hemophilia. Accessed on: May 24, 2012. Available at: http://www.wfh.org/en/page.aspx?pid=646
2Frequently Asked Questions About Hemophilia. World Federation of Hemophilia. Accessed on: May 24, 2012. Available at: http://www.wfh.org/en/page.aspx?pid=637
3Frequently Asked Questions About Hemophilia. World Federation of Hemophilia. Accessed on April 20, 2012 Available at: http://www.wfh.org/en/page.aspx?pid=637
4World Federation of Hemophilia Report on the Annual Global Survey 2010. World Federation of Hemophilia. Accessed on April 20, 2012. Available at: http://www1.wfh.org/publications/files/pdf-1427.pdf
5Lee, 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 April 20, 2012. Screen shot of page available here
6What are Inhibitors (section)? World Federation of Hemophilia. Accessed on December 14, 2012. Available at: http://www.wfh.org/en/page.aspx?pid=651
7Leissinger, Cindy A. Prevention of Bleeds in Hemophilia Patients With Inhibitors: Emerging Data and Clinical Direction. American Journal of Hematology. 2004; 77:187-193.