The first patients in a Phase I clinical trial of Baxter’s lead investigational candidate, BAX 855, a longer-acting (PEGylated) form of a full-length recombinant factor VIII (rFVIII) protein received the new drug earlier today. BAX 855 is based on ADVATE (Antihemophilic Factor Recombinant Plasma/Albumin-Free Method) full-length rFVIII molecule and plasma/albumin-free (PAF) manufacturing process marketed by the company.

ADVATE (derived from the complete FVIII gene) is a recombinant FVIII therapy 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. As a result, there have been no confirmed reports of transmission of HIV, HBV or HCV with rFVIII therapies.

A rare genetic blood clotting disorder
The ADVATE therapy was initially approved by the FDA in July 2003 for control and prevention of bleeding episodes in adults and children with hemophilia A, a rare genetic blood clotting disorder.[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 and primarily affect males.[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] People with hemophilia B (also called Christmas disease) do not have sufficient amounts of clotting factor IX.[2] In about 30% of cases, there is no family history of hemophilia and the condition is the result of a spontaneous gene mutation.[3] According to the World Federation of Hemophilia, more than 400,000 people in the world have hemophilia.[1] All races and economic groups are affected equally.[1]

Clinical Trial
The Phase I trial is a prospective, open-label study that will assess the safety, tolerability and pharmacokinetics of BAX 855 in previously-treated patients aged 12 years or older with severe hemophilia A. When used for prophylaxis, Baxter’s ADVATE requires patients to infuse every two to three days to reduce the occurrence of bleeding episodes. This Phase I trial is the first step in assessing whether BAX 855 can be infused less frequently.

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Treatment regimen
“This trial is designed to provide new insights about our investigational longer-acting FVIII molecule, BAX 855, with the ultimate goal of improving care for patients living with hemophilia A,” said Prof. Hartmut J. Ehrlich, M.D., vice president of global research and development in Baxter’s BioScience business. “The Phase I results will serve as the foundation for advancing this important program through clinical development and determining whether BAX 855 can offer a treatment regimen requiring fewer infusions than ADVATE.”

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PEGylation technology
BAX 855 employs Baxter’s proprietary full-length plasma/albumin-free recombinant protein platform that does not contain any human or animal-derived additives. BAX 855 leverages Nektar Therapeutics’proprietary PEGylation technology, which is designed to extend the duration of activity of proteins and larger molecules. Baxter and Nektar have a collaboration to develop PEGylated products designed to provide new long-acting therapies for hemophilia patients.

Reducing the frequency of bleeding episodes
ADVATE was recently approved for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A. With the inclusion of prophylaxis in the adult patient population, ADVATE became the only antihemophilic factor approved in the United States for prophylactic use in both children and adults. This approval was supported by a Phase IV prophylaxis study sponsored by Baxter demonstrating that ADVATE for routine prophylaxis significantly reduced median annual bleed rates (ABR) in hemophilia A patients. In the study, patients experienced 44 bleeds (per patient per year) during on-demand treatment compared to one bleed (per patient per year) while on either of the prophylactic regimens evaluated, a 98% reduction in annual bleed rate (p<0.0001). Nearly half (42%) of patients experienced zero bleeding episodes during one year on prophylactic therapy. Evaluable patients were those with at least 90% adherence to their prescribed prophylactic regimen.

For more infromation:
[1] What is Hemophilia? World Federation of Hemophilia. Last accessed on 29 June 2011.
[2] Frequently Asked Questions About Hemophilia. World Federation of Hemophilia. Last accessed on: 24 August 2011.
[3] Hemophilia A. National Hemophilia Foundation. Last accessed on 29 June 2011.

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