Clinical Trials
Prophylactic Use of Recombinant Factor VIII Prevents Joint Disease in Young Boys with Hemophilia A
Landmark Study Published in New England Journal of Medicine Demonstrates Benefits of Early Prophylaxis and Suggests New Explanation for Development of Joint Damage in Hemophilia A-------------------------------------------------------------------------
TORONTO, Aug. 9 /CNW/ - Prophylactic (preventive) infusions of recombinant factor VIII (rFVIII) significantly reduce the risk of developing joint damage associated with joint bleeding in young children with hemophilia A, according to a new landmark study published today in the New England Journal of Medicine (NEJM). The findings from the first and only randomized, prospective trial comparing prophylactic(1) with episodic on-demand(2) treatment in children with hemophilia A, showed that 93 percent of children who received prophylactic treatment with recombinant factor VIII had normal joints at the age of six years compared to only 55 percent in the episodic treatment group.
Participants in the five-year clinical trial, known as the 'Joint Outcome Study', used the Kogenate(R) product line, a recombinant factor VIII therapy for the treatment of hemophilia A. In Canada, Kogenate(R) FS is indicated for the treatment of hemophilia A in which there is a demonstrated deficiency of activity of the plasma clotting factor VIII. Kogenate(R) FS provides a means of temporarily replacing the missing clotting factor in order to correct or prevent bleeding episodes. The multicenter study involved 15 academic and major treatment institutions throughout the United States, and included collaboration with the Centers for Disease Control and Prevention and the National Institutes of Health.
"Our results show for the first time that prophylaxis, initiated between six and 30 months of age, is effective at preventing joint bleeds and preserving joint function in young boys with hemophilia A. These results provide healthcare professionals - as well as parents of children with hemophilia A - with solid information to guide optimum treatment," said Marilyn Manco-Johnson, M.D., principal investigator of the study, and director, Mountain States Regional Hemophilia and Thrombosis Center,
University of Colorado at Denver and Health Sciences Center.
Joint damage caused by repeated bleeding into the joints - often referred to as hemophilic arthropathy - is one of the most debilitating and costly consequences of hemophilia A. It can result in long-term inflammation and deterioration of the joint, and ultimately lead to loss of mobility.(3)
However, previous retrospective patient studies have suggested that regular, preventive infusions of factor VIII, given to young patients before they develop permanent joint damage, may reduce the risk of hemophilic arthropathy.(4, 5) The randomized, controlled clinical trial published this week in NEJM provides the strongest medical evidence to date comparing joint outcomes associated with prophylactic and episodic treatment approaches.
"Results from the study indicate the importance of initiating prophylaxis before recurrent bleeding has occurred in individual joints in young boys with severe hemophilia," said Keith Hoots, M.D., study investigator, and professor of pediatrics and division head/pediatric hematology, University of Texas Medical School at Houston.
A subset of patients in the study were identified with joint damage despite an absence or low occurrence of overt bleeds into these joints. The investigators suggest that subclinical bleeds - bleeds that are asymptomatic and often go unnoticed - play a role in the development of joint damage. It is speculated that subclinical bleeds may be prevented through prophylactic infusion.
Early signs of joint damage were detected in the study using state-of-the-art magnetic resonance imaging (MRI) techniques. By the patients' last year in the study (at around five or six years of age), joint and cartilage damage was significantly greater in the episodic group compared to the prophylaxis group.
"Through the donation of 17 million units of our recombinant Factor VIII used to treat the children involved in the trial, Bayer is proud to have been a part of this significant study. We are fully committed to research-driven initiatives that provide data for improving patient care and creating a better quality of life for the thousands of people around the world who live with this often-debilitating disease," said Georg Lemm, MD, PhD, Director of Global Clinical Development, Bayer Schering Pharma.
Further research in the prophylactic treatment of Hemophilia A in young children is also currently on-going at The Hospital for Sick Children in Toronto, Canada and these results will reinforce the need for prophylaxis in young children.
"In Canada, preventive treatment of Hemophilia A with recombinant Factor VIII is widely practiced," said Dr. Victor Blanchette, Chief, Division of Hematolgy/Oncology, Professor of Pediatrics, University of Toronto, The Hospital for Sick Children. "The results of the USA randomized joint outcome study provide solid evidence to guide hemophilia care specialists toward use of prophylactic treatment for young boys with severe hemophilia A."
Joint Outcome Study Methodology
The five-year prospective, multi-center, randomized study was conducted at 15 hemophilia treatment centers in the United States, and enrolled 65 boys with hemophilia A between the ages of 6 months and 30 months. The study was supported by a grant from the Centers for Disease Control and Prevention and
the National Institutes of Health. The Hemophilia and Thrombosis Research Society contributed through the recruitment of participating sites. Bayer HealthCare donated a total of 17 million units of recombinant Factor VIII to treat children for the duration of the trial. The children were randomized to receive either a prophylaxis regimen consisting of 25 IU/kg rFVIII every other day (n=32) or enhanced episodic treatment consisting of at least three doses of rFVIII totaling a minimum of 80 IU/kg at the time of a joint bleed (n=33).
The children were followed until the age of 6 years, when they were assessed for bone or cartilage damage using X-ray and magnetic resonance imaging (MRI) of damage-prone joints (elbows, knees, and ankles). The study also assessed joint function, number of joint hemorrhages, and amount of product consumed.
Detailed Study Findings
Prophylaxis patients had significantly fewer joint hemorrhages per year and overall number of bleeds per year compared to patients on episodic treatment (mean joint bleeds 0.63 vs. 4.89, respectively; mean total bleeds 3.27 vs. 17.69, respectively; P less than 0.001 for both comparisons). When evaluated by MRI at the age of 6 years, 93 percent of children in the prophylaxis group had joints that appeared normal, compared to 55 percent of patients who received episodic treatment (P=0.002). This translated to an 84 percent reduction in the risk for joint damage in patients who received prophylaxis from an early age. The correlation of hemarthroses with joint scores as measured with MRI was weak (r=0.26 with P less than 0.001). Based on MRI, bone or cartilage damage was confirmed in 7 percent of children in the
prophylaxis group compared to 45 percent of those in the episodic group (P=0.002).
About Kogenate(R) FS/KOGENATE(R) Bayer
Kogenate(R) FS (Antihemophilic Factor (Recombinant)) is a recombinant factor VIII treatment. In Canada, Kogenate(R) FS is indicated for the treatment of hemophilia A in which there is a demonstrated deficiency of activity of the plasma clotting factor VIII. Kogenate(R) FS provides a means of temporarily replacing the missing clotting factor in order to correct or prevent bleeding episodes. The most frequently reported adverse events were local injection site reactions, dizziness and rash. Known intolerance or
allergic reactions to constituents of the preparation is a contraindication to the use of Kogenate(R) FS. Known hypersensitivity to mouse or hamster protein may be a contraindication to the use of Kogenate(R) FS/KOGENATE(R) Bayer.
Please see the full prescribing information for important risk and use please visit www.bayer.ca
About Hemophilia A
Hemophilia A, also known as factor VIII deficiency or classic hemophilia, is largely an inherited bleeding disorder in which one of the proteins needed to form blood clots in the body is missing or reduced. Hemophilia A, the most common type of hemophilia, is caused by deficient or defective blood coagulation proteins, known as factor VIII. Hemophilia A is characterized by prolonged or spontaneous bleeding, especially into the muscles, joints, or internal organs. Approximately 400,000 people around the world have hemophilia A.
About Bayer Inc.
Bayer Inc. (Bayer) is a Canadian subsidiary of Bayer AG, an international research-based group with core businesses in health care, crop science, and innovative materials.
Headquartered in Toronto, Ontario, Bayer Inc. operates the Bayer Group's HealthCare and MaterialScience businesses in Canada. Bayer CropScience Inc., headquartered in Calgary, Alberta operates as a separate legal entity in Canada. Together, the companies play a vital role in improving the quality of life for Canadians - producing products that fight diseases, protecting crops and animals, and developing high-performance materials for applications in numerous areas of daily life.
Canadian Bayer facilities include the Toronto headquarters and offices in Ottawa and Calgary. Bayer Inc. has approximately 1,000 employees across Canada and had sales of over $910 million CDN in 2006. Globally, the Bayer Group had sales of over 28 billion Euro in 2006.
Bayer Inc. invested approximately $47 million CDN in research and development in 2006. Worldwide, the Bayer Group spends the equivalent of over 2 billion Euro in 2006 in R&D.
Forward-looking statements
This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties, and other factors could lead to material differences between the actual future results, financial situation, development, or performance of the company and the estimates given here. These factors include those discussed in our public reports filed with the Frankfurt Stock Exchange and the U.S. Securities and Exchange Commission (including our Form 20-F). The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
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(1) Prophylaxis - Regular, continuous infusions to prevent bleeding
episodes and the progression of joint disease.
(2) Episodic on-demand -Treated at the time of and in response to a
bleed.
(3) Manco-Johnson M, et al. Children with hemophilia. Seminars in
Thrombosis and Hemostasis. 2003; vol. 29, number 6: 585-594.
(4) Nilsson IM, et al. Twenty-five years' experience of prophylactic
treatment in severe haemophilia A and B. J Intern Med 1992;
232:25-32.
(5) Manco-Johnson M, et al. Results of secondary prophylaxis in children
with severe hemophilia. Am J Hematol 1994; 47: 113-117.
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/For further information: Dara Willis, Fleishman-Hillard Canada, (416)
645-8179, dara.willis@fleishman.ca; Alison Bing, Bayer Inc., (416) 240-5298,
alison.bing.b@bayer.com
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