DEERFIELD, Ill., January 7, 2013 - Baxter International Inc. (NYSE:BAX) today announced it has submitted an Investigational New Drug (IND) application for its investigational hemophilia A treatment BAX 855 with the U.S. Food and Drug Administration, following positive results from a Phase I trial. BAX 855 is a full-length longer-acting recombinant factor VIII (rFVIII) that was developed to increase the half-life of ADVATE [Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method] – the most widely chosen rFVIII in the world. Baxter expects to start enrollment of adult patients in its Phase II/III study in the first quarter of 2013.
"With our focus on the needs of the hemophilia patient community, Baxter screened more than 100 molecules over several years and has selected one that has the potential to maintain the safety profile and meaningfully extend the half-life of ADVATE to allow for less frequent dosing. Importantly, BAX 855 is the only longer-acting rFVIII in development that is based on a treatment with nearly a decade of patient experience," said Prof. Hartmut J. Ehrlich, M.D., vice president of global research and development in Baxter's BioScience business.
A Phase I prospective, open-label trial assessing the safety, tolerability and pharmacokinetics of BAX 855 was conducted in 19 previously treated patients age 18 years or older with severe hemophilia A who completed the trial. The half-life (measuring the duration of activity of the drug in the body) of BAX 855 was approximately 1.5-fold higher compared to ADVATE. A longer half-life was achieved in all patients in the study using BAX 855, no patients developed inhibitors to either base molecule, BAX 855 or PEG, and no patients had allergic reactions. Eleven adverse events were reported in eight patients across both treatment arms, but none was serious, treatment-related or resulted in withdrawal from the study.
"Efficacy and safety remain the primary goals for choosing a therapy," said Dr. David Bevan, FRCP, Director of the Haemophilia Centre, St. Thomas Hospital, London, UK. "This Phase I study suggests that BAX 855 retains the underlying attributes of ADVATE and has the potential for less frequent dosing, creating a potential new option for hemophilia A patients."
Through a collaboration with Nektar Therapeutics (NASDAQ: NKTR), BAX 855 leverages proprietary PEGylation technology designed to extend the duration of activity of proteins. The technology has been shown to be safe and tolerable, and is used in various approved treatments.
A Phase II/III multi-center, open-label study called PROLONG-ATE will be initiated in the United States during first quarter of 2013 with more than 100 previously treated adult patients with severe hemophilia A to assess the efficacy, safety and pharmacokinetics of BAX 855 for prophylaxis and on-demand treatment of bleeding. Information and enrollment details for the trial are available at www.clinicaltrials.gov or by emailing firstname.lastname@example.org.
ADVATE [Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method] was initially approved by the FDA in July 2003 for control and prevention of bleeding episodes in adults and children (0-16 years) with hemophilia A. ADVATE is a full-length (derived from the complete FVIII gene) recombinant FVIII product that is processed without any blood-based additives. Because no blood-derived components are added at any stage of the manufacturing process, the potential risk of transmitting pathogens that may be carried in blood-based additives is eliminated. There have been no confirmed reports of transmission of HIV, HBV or HCV with rFVIII therapies.
ADVATE is approved in 58 countries worldwide including the United States, Canada, 27 countries in the European Union, Argentina, Australia, Brazil, Chile, China, Colombia, Croatia, Ecuador, Hong Kong, Iceland, Iraq, Japan, Kuwait, Macau, Malaysia, Mexico, New Zealand, Norway, Panama, Puerto Rico, Serbia, Singapore, South Korea, Suriname, Switzerland, Taiwan, Ukraine, Uruguay, and Venezuela.
In the United States, ADVATE [Antihemophilic Factor (Recombinant) Plasma/AlbuminFree Method] is also indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children
(0-16 years) with hemophilia A. ADVATE is the only antihemophilic recombinant FVIII treatment approved in the United States for prophylactic use in both adults and children. ADVATE is not indicated for the treatment of von Willebrand disease.
Detailed Important Risk Information for ADVATE
ADVATE is contraindicated in patients with known anaphylaxis to mouse or hamster protein or other constituents of the product.
Allergic-type hypersensitivity reactions, including anaphylaxis, are possible and have been reported with ADVATE. Symptoms have manifested as dizziness, paresthesia, rash, flushing, face swelling, urticaria, dyspnea, and pruritus. Discontinue use if hypersensitivity symptoms occur and administer appropriate emergency treatment.
Carefully monitor patients treated with AHF products for the development of FVIII inhibitors by appropriate clinical observations and laboratory tests. Inhibitors have been reported following administration of ADVATE predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs).
If expected plasma FVIII levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures FVIII inhibitor concentration.
The serious adverse reactions seen with ADVATE are hypersensitivity reactions and the development of high-titer inhibitors necessitating alternative treatments to FVIII.
The most common adverse reactions observed in clinical trials (frequency greater than or equal to 10 percent of patients) were pyrexia, headache, cough, nasopharyngitis, vomiting, arthralgia, and limb injury.
Please see full prescribing information for ADVATE at: www.baxter.com/downloads/healthcare_professionals/products/ADVATE_PI.pdf
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.3,4 All races and economic groups are affected equally.3,4
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 focuses on optimizing hemophilia care and improving the lives of people worldwide living with bleeding disorders.
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 BAX 855 and related clinical studies. 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; additional clinical results; 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.
1. What is Hemophilia? World Federation of Hemophilia. Accessed on: May 24, 2012. Available at: http://www.wfh.org/en/page.aspx?pid=646
2. Frequently Asked Questions About Hemophilia. World Federation of Hemophilia. Accessed on: May 24, 2012. Available at: http://www.wfh.org/en/page.aspx?pid=637
3.Stonebreaker et al "A study of variations in the reported haemophilia A prevalence around the world" Haemophilia 2010. Jan;16(1):20-32
4.Guidelines for the Management of Hemophilia at WFH website Last Accessed on: December 17,2012 Available at: http://www.wfh.org/en/page.aspx?pid=1270