GENEVA, July 12 /PRNewswire/ -- New preclinical data presented at the 21st Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Geneva, Switzerland, demonstrate that PEGylated forms of recombinant factor VIII(1) (rFVIII) prolong bleeding protection. The studies, conducted by Bayer HealthCare, investigated rFVIII molecule variants in animal models and demonstrated prolonged control of bleeding.
“Developing a longer-acting FVIII product is high on Bayer’s priority list, and the positive findings from our preclinical studies presented this week represent a major step forward,” said Glenn Pierce, MD, PhD, Vice President, Applied Research and U.S. Medical Affairs, Hematology/Cardiology, Bayer HealthCare Pharmaceuticals. “We as a company are committed to innovative research and development of next-generation therapies that produce significant patient benefits. FVIII therapy with prolonged activity could greatly improve patient outcomes through increased ease of compliance and greater access to higher treatment standards at a lower total cost of treatment in the long run.”
The primary approach for prolonging activity involves site-specific PEGylation(2) of a variant of the human FVIII molecule. By adjusting the number and size of PEGylation attachments, as well as the sites of attachment to the FVIII molecule, Bayer scientists have demonstrated an increase in the duration of activity of the PEGylated FVIII molecules in animal models. The PEGylated molecules are also able to retain activity in the presence of specific inhibitors. The following abstracts featured this work:
Site-Specific PEGylation of rFVIII Results in Prolonged In Vivo Efficacy (Murphy, et al: Abstract P-T-022)
This study investigated the attachment of differing molecular weight PEG moieties(3) to specific sites of the rFVIII molecule to determine the effects on plasma half-life and the ability to prevent bleeding in mouse models. Results indicate that site-specific PEGylation can be accomplished and that larger PEG moieties exhibit a significant increase in plasma circulation, up to two-fold, while maintaining efficacy, suggesting that site-specific PEGylation of rFVIII is a viable approach for prolonging activity of rFVIII.
Evaluation of PEG-FVIII Molecules with Prolonged Half-Lives in a Murine FVIII-Dependent Bleeding Model (Liu et al: Abstract P-M-035)
Using a newly developed improved bleeding mouse model, a PEGylated FVIII molecule (PEG FVIII) demonstrated prolonged bleeding protection compared to native rFVIII. For PEGylated FVIII evaluations, animals injured 48 hours after treatment with PEG-FVIII had less animals bleeding (30%) compared with animals injured only 24 hours post rFVIII administration (77%; P=0.0084, Fisher’s Exact Test). Pharmacokinetic studies demonstrated an approximately two-fold increase in half-life for the PEGylated rFVIII versus native rFVIII.
PEGylation Protects Factor VIII from the Inhibition of Antibody Inhibitors (Tang, et al: Abstract P-T-036)
Results from this study demonstrate that, in addition to prolonging bleeding control activity, PEGylation of rFVIII retains increased residual activity in the presence of inhibitors. Specifically, PEG-FVIII was more resistant to inhibitors than native FVIII in four of the eight patient plasma samples tested.
Three additional preclinical abstracts presented this week by Bayer scientists featured additional research focusing on advancing the science and understanding of prolonging biological activity of rFVIII (abstracts P-M-030, P-T-026, and P-T-035). “The research presented at ISTH represents our strong focus on developing major breakthroughs in hemophilia treatment,” said Dr. Pierce.
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.
About Bayer HealthCare AG
Bayer HealthCare AG is one of the world’s leading, innovative companies in the healthcare and medical products industry and based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. The Pharmaceuticals division comprises the following business units: Women’s Healthcare, Diagnostic Imaging, Specialized Therapeutics, Hematology/Cardiology, Primary Care, and Oncology. Bayer HealthCare’s aim is to discover and manufacture products that will improve human and animal health worldwide. The products enhance well-being and quality of life by diagnosing, preventing and treating diseases.
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.
1 Factor VIII -- A large, complex protein that aids in blood clotting and is used to treat hemophilia. 2 PEGylation -- A process intended to lengthen the time a substance remains in the bloodstream without being metabolized and excreted by the body. This is accomplished through the addition of a fat (polyethylene glycol) molecule to the substance. 3 Moieties -- A part or section of the whole molecule.
Bayer HealthCare
CONTACT: Sreejit Mohan of Bayer HealthCare, +1-510-705-5477,Sreejit.mohan@bayer.com
Web site: http://www.bayer.com/
