European Medicines Agency Approves SmPC Change to Baxter's ADVATE to Include Information on PK-Guided Dosing Study

Press Release:
  Jul 23, 2013 — LONDON, ENGLAND - Baxter International Inc. (NYSE:BAX) today announced that the European Medicines Agency has authorized an update to the Summary of Product Characteristics (SmPC) for Baxter's ADVATE [Antihemophilic Factor (Recombinant) Plasma/Albumin Free Method, (in the EU, ADVATE, octocog alfa)] to include findings of the Phase IV prophylaxis study.

The pharmacodynamic properties section of the updated European SmPC now describes the findings of an ADVATE Phase IV prophylaxis study that compared standard and pharmacokinetic (PK)-guided prophylaxis dosing regimens to on-demand treatment with ADVATE. PK-guided prophylaxis is based on each individual's response to clotting factor. In the study (which supported the approval of the prophylactic dosing of ADVATE in the United States in 2011), of the two prophylactic regimens evaluated, the pharmacokinetic-driven regimen offered some patients the option of a dosing schedule of every three days. The clinical data demonstrated that PK-guided and standard prophylactic dosing regimens were comparably effective in reducing annual bleeding rates (ABR).1

"Importantly, this addition to our ADVATE SmPC offers clinicians and patients in Europe information about pharmacokinetics that may enable them to better personalize their treatment regimens with the goal of fewer infusions per year while still effectively reducing bleeds," said Anders Ullman, M.D., Ph.D., vice president of global research and development in Baxter's BioScience business.
In the prophylaxis study, an individualized pharmacokinetic guided dosing regimen (within a range of 20 to 80 IU of factor VIII per kg body weight at intervals of 72 ± 6 hours, n=23) was compared with a standard prophylactic dosing regimen (20 to 40 IU per kg every 48 ±6 hours, n=30) in previously-treated patients with Hemophilia A. The results showed a 98 percent reduction in annual bleed rate compared to the previous on-demand treatment period; 42 percent of patients experienced zero bleeds during one year on either of the prophylaxis regimens.

In Europe, for long-term prophylaxis against bleeding in patients with severe hemophilia A, the usual doses are 20 to 40 IU per kg body weight at intervals of two to three days. In patients under the age of six, doses of 20 to 50 IU of factor VIII per kg body weight three to four times weekly are recommended.

ADVATE [Antihemophilic Factor (Recombinant) Plasma/Albumin Free Method, (in the EU, ADVATE, octocog alfa)] is indicated for the treatment and prophylaxis of bleeding in patients with hemophilia A (congenital factor VIII deficiency.) 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 therapies.

ADVATE is approved in 59 countries worldwide including the United States, Canada, 28 countries in the European Union, Argentina, Australia, Brazil, Chile, China, Colombia, Ecuador, Hong Kong, Iceland, Iraq, Japan, Kuwait, Macau, Malaysia, Mexico, New Zealand, Norway, Panama, Puerto Rico, Serbia, Singapore, South Korea, Suriname, Switzerland, Taiwan, Tunisia, Ukraine, 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 factor VIII 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:

About Hemophilia A
Hemophilia is a rare genetic2 blood clotting disorder and the most severe forms of the disease primarily affect males.3 People living with hemophilia do not have enough of, or are missing, one of the blood clotting proteins naturally found in blood.4 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 According to the World Federation of Hemophilia, it is estimated that more than 400,000 people in the world have hemophilia.6 All races and economic groups are affected equally.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.

1Valentino 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.
2How do you get hemophilia? World Federation of Hemophilia. Accessed on: June 3, 2013. Available at:
3Frequently Asked Questions About Hemophilia. World Federation of Hemophilia. Accessed on: June 3, 2013. Available at:
4What is Hemophilia? World Federation of Hemophilia. Accessed on: June 3, 2013. Available at:
5Lee, 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.
6Treatment. World Federation of Hemophilia. Accessed on June 3, 2013. Available at:
7What is Hemophilia? Hemophilia Federation of America. Accessed on June 3, 2013. Available at:
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Tags: Hemophilia, ADVATE, pharmacodynamic, Baxter
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