Long-Term Factor IX Expression and Improved Blood Clotting Time Achieved
SEATTLE, WASHINGTON (May 28, 1998): Scientists at Avigen, Inc. (Nasdaq: AVGN), and The Children's Hospital of Philadelphia have developed a gene therapy approach for the treatment of hemophilia B using a single intramuscular administration of an adeno-associated virus (AAV) vector containing the gene for coagulation factor IX. Katherine A. High, M.D., a hematologist at The Children's Hospital of Philadelphia and Avigen scientific advisor, will present research at the inaugural meeting of the American Society of Gene Therapy that shows the ability of AAV-mediated gene therapy to achieve sustained production of factor IX resulting in improved blood clotting times in a large animal model of hemophilia B.
"These results are very exciting, and can validate that AAV vectors in this model can provide sustained and long-term expression--something that other gene therapy systems have had limited success demonstrating," said John Monahan, Ph.D., president and chief executive officer of Avigen, Inc. "Based on these results and additional R&D advances at Avigen, we are working closely with Dr. High to develop this therapy further with the objective of initiating a human clinical trial as early as the end of calendar 1998 which, if successful, will represent a major advance in the treatment of hemophilia B."
"Our work extends previous results obtained in mice to a well-defined, naturally occurring, large animal model of hemophilia B that is very similar to the disease in humans," commented Dr. High. "This is the first example of the intramuscular administration of a gene therapy vector resulting in sustained improvement of the clotting abnormality in hemophilia and is an important step in justifying this approach for the treatment of patients with hemophilia B."
A single intramuscular administration of an AAV vector containing the gene for factor IX was given. The animals showed long-term production of factor IX in a dose-related manner with plasma levels of factor IX being increased for approximately nine months with observations continuing. Researchers observed a partial correction of the whole blood clotting time and partial thromboplastin time, another laboratory test to measure clotting time. Also, there was no toxicity noted in treated animals.
Hemophilia B
Hemophilia B, the second most common severe genetic bleeding disorder worldwide, is caused by an abnormality or deficiency in the blood clotting protein factor IX. To treat or prevent serious bleeding episodes, patients currently receive intermittent or regularly scheduled infusions of factor IX obtained from pooled human plasma or produced by recombinant DNA technology. Such treatments can cost up to $100,000 per year, are inconvenient, and for many individuals do not provide adequate control over their bleeding. Individuals with hemophilia B over time may suffer from spontaneous bleeding episodes which can lead to crippling joint deformities and intracerebral bleeding which can be fatal. Using gene therapy to enable individuals with hemophilia B to manufacture constant levels of factor IX could potentially protect patients from the long-term debilitating effects of their disease, as well as greatly lower the cost of current treatments.
Background on AAV Vectors
Avigen's AAV vectors are derived from adeno-associated virus, a non-pathogenic human virus. The company produces AAV vectors by removing the virus's own genes and replacing them with genes for therapeutic proteins. AAV vectors combine desirable properties of viral and non-viral vectors and may offer potential advantages over other gene therapy vectors. These advantages include efficient delivery of genes to both dividing and non-dividing target cells, absence of viral genes that may be responsible for causing an undesirable immune response, high levels of gene expression, and stability which allows them to be administered directly into patients and to be manufactured, stored and handled like traditional pharmaceutical products. Avigen's scientists have developed a proprietary manufacturing process that improves AAV vector manufacturing and achieves increased yields.
Avigen, Inc., is a biotechnology company involved in the development of gene therapy products derived from adeno-associated virus for the treatment of inherited and acquired diseases. The Company's proposed gene therapy products are designed for in vivo administration to achieve the production of therapeutic proteins within the body. Avigen is focusing its efforts on developing products to deliver genes for the treatment of hemophilia, brain cancer, Parkinson's disease, metabolic storage diseases, and hyperlipidemia.
The Children's Hospital of Philadelphia, the nation's first children's hospital, is a leader in patient care, education, and research. This 304-bed multispecialty hospital provides comprehensive pediatric services to children from birth to age 19.
Except for the historical information contained herein, this news release contains forward-looking statements that involve risks and uncertainties. The Company's actual results may differ materially from those discussed herein. Factors that could cause or contribute to such differences include, but are not limited to, those discussed in this press release, as well as other risks detailed from time to time in documents filed by Avigen with the SEC, including the report on Form 10K/A for the year ended June 30, 1997.