By Kim Coghill
Avigen Inc.¿s stock took a hit Monday in response to the company temporarily stopping its Phase I/II Coagulin-B gene therapy trial in hemophilia B.
Avigen¿s stock (NASDAQ:AVGN) closed Monday at $10.52, down $4, or 27.5 percent.
John Monahan, Avigen¿s CEO, told BioWorld Today the trial was halted because trace amounts of the vector were found in the patient¿s semen. The trial protocol requires the company to stop the trial, which involves one 65-year-old patient. Monahan said Avigen has told the FDA it will stop the trial for at least two weeks while it observes the patient and waits for the semen to clear.
Coagulin-B uses an adeno-associated virus (AAV) to deliver Factor IX, the missing or deficient protein that causes hemophilia B. In a previous study of eight patients, Coagulin-B was delivered via intramuscular injection, but in this trial it was delivered to the liver.
¿The idea here is to put the AAV into the body to get the production of Factor IX into the blood of these patients,¿ Monahan said. ¿We can work with any tissue, but we chose the muscle, which is very convenient, and the liver, where Factor IX is normally made. As it turns out it, Factor IX to the liver is more potent.¿
When injecting a product into the body, Monahan said anything not being taken up by the cells ¿just sloshes around the body and over a few days decreases and is excreted out in the urine. In this case we found a presence [of the vector] in the blood and even in the saliva, but it disappeared after a few days. We were surprised when we found it in the semen. It was not in the sperm.¿
Monahan did not elaborate on a possible reason. However, Fariba Ghodsian, managing director of health care research for Roth Capital Partners LLC in Los Angeles, said the event could be age-related.
Ghodsian said the vector was present in many tissues early on, but may have remained in the semen because of lower sperm production.
¿So far we have not seen a safety problem. The problem is ethical ¿ the question is will this spread the disease to the offspring?¿ Ghodsian said.
Ghodsian said offspring would not be affected because the vector has not been identified in mobile sperm.
The temporary stop in the trial should not have a major impact on the study, Monahan said. ¿It will slow the progression of this particular study. From a perspective of what¿s going on in terms of AAV, we need to look more closely at where the vector goes in the body when it is delivered like this.¿
AAV is a small, stable and non-pathogenic virus, to which a majority of the population has been exposed, and has never been associated with a disease. The company uses a modified form of this virus to carry a therapeutic gene into a target. The goal is that once inside the cell, the therapeutic gene starts to act like any other gene in a cell and produces the protein product corresponding to the gene delivered.
Avigen and Bayer AG, of Leverkusen, Germany, formed a $60 million alliance to market and commercialize Coagulin-B. Last year Bayer said it expected to file a biologics license application in 2005. (See BioWorld Today, Nov. 20, 2000.)