Summer 1999 - Factor Nine News

From The Coalition for Hemophilia B

Avigen Inc. begins phase I of clinical trials for treatment of Hemophilia B

The first solid evidence that gene therapy can effectively correct the defect causing hemophilia B in a large animal model was presented at the plenary session of the American Society of Hematology (ASH) on Sunday, December 6, 1998 in Miami Beach, FL. and at a special symposium entitled “Progress Towards Hemophilia Gene Therapy” on June 10, 1999 at the American Society for Gene Therapy meeting in Washington, DC. The new gene therapy uses a proprietary adeno-associated Virus (AAV) vector delivery system, developed by Avigen, Inc. Based on the findings presented in Miami, researchers at The Childrens’s Hospital of Philadelphia, and Stanford University Medical Center collaborating with Avigen, have begun Phase I trial with nine hemophilia B patients for the AAV-mediated gene transfer.

Dr. Mark Kay of Stanford University Medical Center and Dr. Katherine High of The Children’s Hospital are both involved in the trials. They are also members of Avigen’s Medical and Scientific Advisory Board. Both highly respected doctors are sure to strengthen the company’s research efforts toward treating hemophilia. “With Dr. High’s expertise in clinical and molecular aspects of hemophilia and Dr. Kay’s expertise in vector development related to gene delivery for hemophilia, we feel we have a superb team in place.” stated Dr. John Monahan, Avigen’s President and CEO.

Avigen is the first company to use the AAV Vector for a potential hemophilia therapy. AAV is often called “The benevolent virus” (which is a harmless virus - never associated with any disease of any kind but that acts as a delivery system). The viruses’ own DNA is removed first and then the DNA for factor IX is inserted. Once this process is completed the patient receives a procedure called a single intramuscular administration (an injection in the muscle) which takes about 10 - 15 minutes. The vectors that contain the correct genetic code for factor IX production are now absorbed by the patients cells. The cells immediately take up the vector and deliver the healthy genetic instructions that tell the cells to produce the factor IX. Now the cells contain the instructions and will start to produce the factor IX protein which will then start circulating in the blood. The cells are now constantly producing the factor IX.

The results of a preclinical study of 6 dogs at The University of North Carolina at Chapel Hill have shown that within 4-8 weeks after a single administration of the AAV vector, the dogs produced near normal clotting times. Now two years later they have the same reaction. Normal clotting time for these dogs were within 15 - 20 minutes. Compared to 60 minutes or more prior to treatment.

This is the first trial with humans. The trial will last between 9 - 12 months. The patients with hemophilia B will be divided into three equal groups and receive dosages in the amount of low, medium and high.

While there is no human data as yet, Avigen is hopeful that standard therapy would entail an initial injection and then booster shots every 6 months to a year. But the ultimate course of therapy will not be determined until the clinical trials are concluded.

Further information regarding phase one should be available early next year. We will try to keep you up to date on this. Avigen is also working on a similar approach to treat hemophilia A, as well as other illnesses.

Note:: DNA is the genetic makeup (like a blueprint) which tells the cells to produce clotting factor. What Avigen is doing is inserting the missing genes into the patients cells so that the cells will then have the genetic code and from then on these cells will produce the blood clotting factors themselves. Basically, this is putting the correct genetic blueprints back into the patient!

*****************

Congratulations to:

Novo Nordisk for the FDA approval of the Recombinant VIIA - which will help people with Hemophilia A or B who have inhibitors.

Centeon Inc. for the FDA approval of Humate-P for treatment of von Willenbrand’s disease which will greatly help those who suffer from that condition.

The dates for FAMOHIO, in Columbus Ohio are July 30 - August 1. We will have a stand and look forward to seeing you there.