Clinical Data Suggest Decreased Bleeding Risk in People With Severe Hemophilia A While Maintaining Factor VIII Levels Above One Percent
GENEVA, July 10, 2007 /PRNewswire-FirstCall/ -- Baxter Healthcare Corporation today announced the presentation of findings from the ADAPT (Analysis of Data from ADVATE(R) Prospective Trials) study program database showing a statistically significant relationship between the duration of time spent with factor VIII blood levels below one international unit per deciliter (1 IU/dL, one percent of normal factor VIII level) and an increase in the annual bleed rate in people with hemophilia A. The findings from ADAPT suggest that maintaining trough levels above 1 IU/dL with prophylactic therapy may decrease the number of bleeding episodes, particularly in children.
"Until now there has been insufficient clinical evidence to demonstrate that factor VIII levels less than 1 IU/dL are associated with increased bleeding in patients receiving prophylaxis for the management of hemophilia A," said Peter W. Collins M.D., FRCP, FRCPath, Department of Haematology, University Hospital of Wales, Cardiff, U.K.
"These results suggest that decreasing the amount of time a patient spends with a factor VIII less than 1 IU/dL will reduce the number of bleeds. This can be achieved in part by improving adherence to prescribed prophylaxis, while measurement of trough factor VIII levels in some patients may help individual tailoring of factor VIII dosing regimens."
Dr. Collins presented data from the ADAPT group showing an analysis of 48 children (one to six years of age) and 100 adolescents and adults (10 to 65 years of age) with severe hemophilia A and factor VIII levels less than 1 IU/dL who participated in ADVATE clinical trials. All participants were initially evaluated in a 48-hour pharmacokinetic study to measure their rate of clearance of ADVATE prior to initiation of prophylactic therapy. The 10 to 65 years old group was treated for 75 exposure days on a fixed prophylactic regimen of 25-40 IU/kg 3-4 times a week irrespective of bleeding. Prophylaxis could be modified by the physician (or investigator) for the one to six year old group.
By analyzing individual pharmacokinetic data and doses infused, Collins and coauthors were able to estimate the median number of hours per week spent below the 1 IU/dL trough level for each population, 19.7 hours and 16.5 hours for the one to six year old and 10 to 65 years old groups respectively. Subsequent comparison with bleed frequency for each group found that in the one to six years of age group the time below 1 IU/dL while on prophylaxis was associated with increased incidence of traumatic and spontaneous total bleeds (p<0.0001). Similarly in subjects that remained on a fixed prophylactic regimen in the 10 to 65 years age group, the duration of time below 1IU/dL was associated with increased total and joint bleeds (p<0.02).
"ADAPT continues to generate important information relating treatment with outcomes for people with hemophilia A," said Bruce Ewenstein, M.D., Ph.D., global medical director for hemophilia therapies at Baxter. "These data from the ADVATE clinical program have provided valuable insight into the potential role of maintaining trough levels above 1 IU/dL to reduce the risk of breakthrough bleeding."
Additionally, a poster presentation of data from ADAPT, results showed that bleeding patterns in people with severe hemophilia using standard prophylaxis therapy vary according to age groups. For both adolescents and adults, joint bleeds were more likely to occur in the summer, possibly due to increased physical activity. Furthermore, in patients on a Monday-Wednesday- Friday dosing schedule, a greater number of joint bleeds occurred on Sundays, reaching statistical significance in adults (18 to 65 years of age). The results support the concept of individual tailoring of prophylactic regimens according to activity and bleeding patterns.
About Hemophilia A
People with hemophilia A do not produce adequate amounts of factor VIII, which is necessary for blood to effectively clot. If untreated, patients with severe hemophilia A have a greatly reduced life expectancy. According to the World Health Organization, more than 400,000 people in the world have hemophilia, corresponding to a prevalence of 15 to 20 in every 100,000 males born worldwide.
The ADAPT (Analysis of Data from ADVATE Prospective Trials) research program was initiated to further investigate and explore the expanding ADVATE clinical study program database for additional insight into general hemophilia medical research and practice issues beyond the main goals of the Investigational New Drug (IND) research program. ADAPT research goals include examining the reliability and reproducibility of certain pharmacokinetic (PK) measurements across a broad population of subjects. Such PK data may be important to clinical development and evaluation of new therapeutics, as well as for the prediction of relationships to clinical outcomes and their utility in optimizing the routine clinical management of hemophilia A. These studies may offer guidance for designing individualized dosing regimens based on patient PK profiles, which may allow for less frequent infusion requirements or improved treatment outcomes.
It is important to note that prophylaxis is not an approved therapy regimen in some countries, including the United States. On-demand is the approved dosage regimen for most factor VIII therapies in the United States.
ADVATE is currently approved for use in the United States, Australia, Japan and Europe.
ADVATE is indicated in hemophilia A (classical hemophilia) for the prevention and control of bleeding episodes. ADVATE is also indicated in the perioperative management of patients with hemophilia A. ADVATE is not indicated for the treatment of von Willebrand's disease. Infused directly into the bloodstream, ADVATE works by temporarily raising the level of factor VIII in the blood, thus allowing the body's blood clotting process to properly function. ADVATE is the only recombinant factor VIII therapy processed without blood or blood additives, including human albumin or other plasma protein additives.
ADVATE should be administered cautiously in patients with previous hypersensitivity to constituents of factor VIII preparations or known sensitivity to mouse or hamster proteins.
The most common related adverse reactions observed during the ADVATE clinical studies include: strange taste in mouth, headache, dizziness and flushing. The formation of inhibitors has been observed with all factor VIII concentrates, including ADVATE.
Patients and caregivers in the United States can obtain more information on ADVATE, including full Prescribing Information, at http://www.ADVATE.com. European healthcare professionals can obtain information at http://www.emea.europa.eu
Baxter Healthcare Corporation is the principal U.S. operating subsidiary of Baxter International Inc. . Baxter International Inc., through its subsidiaries, assists healthcare professionals and their patients with the treatment of complex medical conditions, including cancer, hemophilia, immune disorders, kidney disease and trauma. The company applies its expertise in medical devices, pharmaceuticals and biotechnology to make a meaningful difference in patients' lives.
This release includes forward-looking statements with respect to the use of factor VIII to decrease the number of bleeding episodes experienced by patients with hemophilia A including the use of prophylaxis therapy. 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 for the timely enrollment and commencement of additional clinical studies; additional clinical results demonstrating the safety and efficacy of the therapies; market acceptance of such therapies; and other risks identified in the company's most recent filing on Form 10-K and other SEC filings, all of which are available on the company's web site. The company does not undertake to update its forward-looking statements.
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Posted: July 2007