Prevention and eradication of FVIII antibodies could improve hemophilia treatment

Octapharma AG is leading an international initiative focused on confronting the major risk associated with hemophilia A therapy - anti-factor VIII (FVIII) antibodies, also known as inhibitors. This initiative, combined with Octapharma's efforts to pursue the first recombinant FVIII therapy produced from a human cell line, could dramatically impact the treatment of an estimated one in every 5,000 to 10,000 men born with hemophilia A worldwide. Globally, 75% of the hemophilia cases go undiagnosed or untreated.

Octapharma AG, the third largest plasma products manufacturer in the world, recently brought together many of the most respected blood coagulation disorder researchers for two symposia on this important issue during the International Society on Thrombosis and Haemostasis (ISTH) Biennial Congress in Boston. Octapharma was one of only five Platinum Sponsors at the ISTH Congress, which attracted approximately 7,500 representatives of the medical and research community as well as many patients.

Clinical experts noted during the symposia that up to 40 percent of previously untreated patients (PUPs) with hemophilia A develop the most serious clinical complication of FVIII replacement therapy - inhibitory antibodies - which can result in uncontrolled hemorrhage, increased hospitalizations and joint damage, resulting in increased morbidity and mortality.

"We brought the international community together to confront this issue because our worldwide commitment to hemophilia A patients dates back to Octapharma's formation 25 years ago," said Octapharma AG Vice Chairman Kim Bjornstrup. "Our first therapies were developed for the hemophilia community and today most hemophilia patient advocates say that inhibitor development is the greatest obstacle to effective treatment. Octapharma is focused on introducing innovative development strategies that will help improve patient quality of life by finding an effective treatment and developing products to overcome this obstacle."

The Octapharma-sponsored symposium "Prevention and Eradication of FVIII Inhibitors: Bridging Lab and Field Research" was chaired by David Lillicrap, M.D., Professor of Pathology and Molecular Medicine at Queen's University in Ontario, Canada, and Georges E. Rivard, M.D., Professor of Pediatrics at Universite de Montreal. The symposium provided an opportunity for discussing recent data supporting the use of von Willebrand factor (VWF)/FVIII concentrates for Immune Tolerance Induction (ITI) in hemophilia A patients with poor prognosis for a successful ITI outcome.

Presenters reviewed a balanced mix of clinical, preclinical and basic data on the role of the presence of VWF in FVIII concentrates and the clinical experience on prevention and eradication of FVIII inhibitors. In addition, the most recent prospective and retrospective clinical data obtained with different classes of FVIII concentrates used for ITI treatment were presented along with an update on the progress of the ongoing prospective study designed to further investigate the risk of FVIII inhibitor development in previously untreated patients with hemophilia.

"A growing body of clinical experience suggests that VWF-containing pdFVIII concentrates increase the likelihood of successful tolerization, particularly in patients with poor prognostic factors," said symposium presenter Wolfhart Kreuz, M.D. of the Hemophilia Comprehensive Care Centre at Johann Wolfgang Goethe University Hospital in Frankfurt, Germany. "Successful ITI leads to normalization of the FVIII half-life, allows fully effective on-demand replacement therapy and prophylaxis, with consequent improvement in the patient's quality of life and a marked reduction in the cost of treatment."

The Octapharma-sponsored symposium "From Humans to Humans - Introducing the First Recombinant FVIII Produced From a Human Cell Line" was chaired by Edward G.D. Tuddenham, M.D., Director of The Katharine Dormandy Haemophilia Center & Thrombosis Unit in London, and Johannes Oldenburg, M.D., Ph.D., Chairman and Director of the Institute of Experimental Haematology and Transfusion Medicine in Bonn, Germany.

"Twenty years after the start of clinical trials with rFVIII concentrates expressed by hamster cells, a new rFVIII compound has recently entered clinical studies," Dr. Tuddenham said. "The primary goal behind the development of this new rFVIII was to reduce the overall immunogenic challenge (and resultant inhibitor formation) to the hemophilia patient during rFVIII replacement therapy. An essential part of this strategy was the development of a human rFVIII protein expressed in a human cell-based protein expression system instead of using existing hamster-derived cell lines."

The symposium highlighted the benefits of using a human cell-based protein; preclinical characterizations and some of the functional properties of the first recombinant factor VIII (rFVIII) from a human cell-line; and the planned global clinical development program with the new rFVIII derived from human cells. The investigational new drug application for Octapharma's human cell line rFVIII was filed in the U.S. in May 2008. Clinical trials started in Russia in Spring 2009 and are expected to start in the U.S. later this year. Additionally, Octapharma has other recombinant human cell line products in various stages of development.

During the symposium, possible advantages of using a human cell line for recombinant FVIII production were presented. Those include the absence of the rodent antigenic epitopes Gal-1,3-Galactose and N-glycolyl-neuraminic-acid on the FVIII-protein, which could lead to a reduced immunogenicity compared to currently marketed recombinant factor VIII products that are all derived from hamster cell lines and also to a potentially increased tolerability.