Baxter Reports Results of ADVATE Real-World Experience from Worldwide Post-Marketing Database of Hemophilia A Patients

AMSTERDAM, Netherlands - Baxter International Inc. (NYSE:BAX) today presented two comprehensive analyses supporting the proven clinical and real-world results of ADVATE [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method] during the 24th Annual Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Amsterdam, The Netherlands. The presentations include two complementary studies of the ADVATE profile, including an analysis of post-marketing data from approximately 1,200 hemophilia A patients across 15 countries as well as safety findings from a 10-year database of 12 clinical trials.

A meta-analysis of post-authorization safety studies (PASS) (abstract# PO148) presented at ISTH supports the overall product safety and effectiveness profile, as well as low rate of inhibitor development with ADVATE, with only one de-novo inhibitor in severe previously-treated patients (n=669) with more than 150 prior exposure days [1]. The analysis assessed the effectiveness of ADVATE treatment in non-controlled, real-world clinical practice, and found that the median annual bleed rate (ABR) for patients on continuous prophylaxis (twice a week or more, n=560) was 1.67, which supports the ABR reported in controlled clinical studies. The effectiveness result in the study captured ADVATE efficacy in routine clinical practice (as opposed to efficacy, which measures in a controlled, interventional trial setting). The meta-analysis included patients from the United States, Australia, Japan, and 12 countries in Europe, who were followed for more than one year with exposure to ADVATE ranging between 85 and 103 mean exposure days across five studies [1].

"This meta-analysis of the post-market surveillance database, the largest available in hemophilia today, demonstrates a global patient experience with ADVATE that is consistent with the results reported in our highly controlled clinical programs," said Bruce Ewenstein, M.D., Ph.D., vice president of clinical affairs for Baxter. "Given the broad range of patients and hemophilia clinical practice around the world, it is significant that these data continue to support the low inhibitor rate among patients using ADVATE as well as the effectiveness of bleed prevention when on an ADVATE prophylaxis regimen."

Also presented at ISTH, a database of more than ten years of ADVATE clinical data provided an integrated analysis of safety data from 12 clinical interventional studies (abstract #812)[3]. The studies included more than 400 patients with hemophilia A, with roughly 90 percent of patients receiving prophylaxis treatment with ADVATE and a mean of 97 exposure days.

The integrated safety analysis confirmed previously demonstrated safety and tolerability in children and adults with moderately severe or severe hemophilia A in a wide variety of clinical settings, and revealed no new safety signals. The overall incidence of FVIII inhibitors in previously-treated patients, (PTPs, over 50 exposure days) was 0.4 percent. Only one low-titer inhibitor was detected in PTP population who had at least 10 exposures to the product during their respective studies (n=276). In the full safety analysis of 418 patients (both PTPs and previously-untreated patients, or PUPs), there were no adverse events leading to study withdrawal, no hypersensitivity and no anaphylaxis/anaphylactoid reactions [3].

"The ADVATE treatment data collected from 12 interventional clinical trials over the past decade has allowed researchers to verify and confirm the established safety and efficacy profile of this product," said Amy Shapiro, M.D., medical director at the Indiana Hemophilia and Thrombosis Center and lead investigator of the integrated analysis. "The data we analyzed supports the established safety record of ADVATE, and importantly, will give clinicians continued confidence in prescribing ADVATE for their patients."

About ADVATE
ADVATE [Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method] is indicated for the control and prevention of bleeding episodes in adults and children (0-16 years) with hemophilia A. ADVATE 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 not indicated for the treatment of von Willebrand disease.

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 treatments.

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, Hong Kong, Iceland, Iraq, Japan, Macau, Malaysia, New Zealand, Norway, Panama, Puerto Rico, Serbia, Singapore, South Korea, Suriname, Switzerland, Taiwan, Uruguay and Venezuela.

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 subjects) were pyrexia, headache, cough, nasopharyngitis, vomiting, arthralgia, and limb injury.

Please see full prescribing information for ADVATE at: http://www.baxter.com/downloads/healthcare_professionals/
products/ADVATE_PI.pdf

About Hemophilia A
Hemophilia is a rare genetic4 blood clotting disorder and the most severe forms of the disease primarily affect males [5]. People living with hemophilia do not have enough of, or are missing, one of the blood clotting proteins naturally found in blood [6]. 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 [6]. Without enough FVIII, people with hemophilia can experience spontaneous, uncontrolled internal bleeding that is painful, debilitating, damaging to joints and potentially fatal [5,7]. According to the World Federation of Hemophilia, it is estimated that more than 400,000 people in the world have hemophilia [8]. All races and economic groups are affected equally [9].

About Inhibitors
As many as one-third of patients with severe or moderately severe hemophilia A are at risk for developing inhibitors [10], which are antibodies produced by the body's immune system in response to factor replacement therapy [11]. Inhibitors cause the body to work against the factor replacement therapy, neutralizing its effect and preventing an individual's blood from clotting [10]. 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 [10].

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.

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[1] 2013 ISTH Congress. E-poster presentation. Meta-analysis of Post Authorization Safety Studies (PASS): Worldwide postmarketing surveillance of hemophilia A patients treated with antihemophilic factor recombinant plasma/albumin-free method rAHF-PFM.
[2] Valentino LA, Mamonov V, Hellmann A, Quon DV, Chybicka A, Schroth P, Patrone L, Wong W-Y for the Prophylaxis Study Group. A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management. J Thromb Haemost 2012; 10: 359-67.
[3] 2013 ISTH Congress. E-poster presentation. Integrated Analysis of Safety Data from 12 clinical interventional studies of a Plasma- and Albumin-free Recombinant Factor VIII (rAHF-PFM) in Persons with Hemophilia A.
[4] How do you get hemophilia? World Federation of Hemophilia. Accessed on: June 3, 2013. Available at: http://www.wfh.org/en/page.aspx?pid=644
[5] Frequently Asked Questions About Hemophilia. World Federation of Hemophilia. Accessed on: June 3, 2013. Available at: http://www.wfh.org/en/page.aspx?pid=637
[6] What is Hemophilia? World Federation of Hemophilia. Accessed on: June 3, 2013. Available at: http://www.wfh.org/en/page.aspx?pid=646
[7] Lee, C. A. Hemophilia Care in the Modern World, in Current and Future Issues in Hemophilia Care (eds E.-C. Rodríguez-Merchán and L. A. Valentino), 2011.
[8] Treatment. World Federation of Hemophilia. Accessed on June 3, 2013. Available at: http://www.wfh.org/en/page.aspx?pid=642
[9] What is Hemophilia? Hemophilia Federation of America. Accessed on June 3, 2013. Available at: http://www.hemophiliafed.org/bleeding-disorders/hemophilia/
[10] Leissinger, Cindy A. Prevention of Bleeds in Hemophilia Patients With Inhibitors: Emerging Data and Clinical Direction. American Journal of Hematology. 2004.
[11] What are Inhibitors? World Federation of Hemophilia. Accessed on June 3, 2013. Available at: http://www.wfh.org/en/page.aspx?pid=651

For more information:

• http://www.baxter.com/downloads/healthcare_professionals/

Tags: ADVATE, Thrombosis, Haemostasis, hemophilia