Officials at Avigen Inc. discontinued a seven-patient Phase I study for Coagulin-B, a gene therapy under clinical investigation for hemophilia B, after two patients experienced mild elevations in liver enzymes leading the company to believe there was no therapeutic window.
Avigen, and partner Bayer Biological Products Division, a unit of Bayer AG, of Leverkusen, Germany, are planning discussions to determine the best way of moving forward with the candidate, Kenneth Chahine, president and CEO of Alameda, Calif.-based Avigen Inc., told BioWorld Today.
Coagulin-B uses an adeno-associated virus (AAV) to deliver Factor IX, the missing or deficient protein that causes hemophilia B.
"We would not necessarily look at another indication, rather we may look at a slightly modified drug or deliver the drug into a different target, or we may use a different delivery method," Chahine said. "[We would consider] whether there is a way to avoid this very mild toxicity and still get the therapeutic benefit."
Chahine cautioned that mild liver toxicity was not forcing the firm to stop the trial, rather the problem is that "[Factor IX] expression decreases coincident with the enzymes going up."
Furthermore, Chahine said the first patient with elevated liver enzymes achieved greater than 10 percent of normal Factor IX expression. "For all intents and purposes, that patient was cured for four weeks, until the levels then went down. This is hard because on the one hand we showed that we could get some really fantastic levels. Unfortunately, when we get to toxicity, we get this decrease in expression," he said, adding that the liver toxicity level in one patient was so low that the firm was not required to notify the FDA.
Avigen's stock (NASDAQ:AVGN) Friday fell 9.2 percent, or 36 cents, to close at $3.54. By comparison, Avigen's stock fell 27.5 percent, or $4, to close at $10.52 in October 2001 when the company stopped its Phase I/II Coagulin-B trial after trace amounts of the vector were found in a patient's semen. (See BioWorld Today, Oct. 9, 2001.)
The decision to stop the trial this time has caused Avigen to shift its focus to its two neurological product candidates: AV201 for the treatment of Parkinson's disease and AV333 for the treatment of severe chronic pain.
Avigen has filed an investigational new drug application to begin clinical testing on AV201, which initially will be administered to people in the late stages of Parkinson's disease who have exhausted most of their therapeutic options.
Meanwhile, AV333 is being developed as a nonviral DNA-based drug.
At the end of March, Avigen reported about $94 million in cash, enough to last three and a half to four years, Thomas Paulson, the company's chief financial officer, told BioWorld Today. "This news may adjust our burn rate a little, but it will probably stay relatively flat," he said.
The deal between Avigen and Bayer to develop and commercialize Coagulin-B was valued at $60 million when it was signed in late 2000. At the time, Bayer purchased $15 million in Avigen stock, and since then has paid Avigen $2.5 million. Overall, the collaboration includes milestone payments, funding of the clinical trial and AAV vector manufacturing cost. Avigen also is poised to receive a royalty on net sales for its intellectual property, as well as a share of Coagulin-B sales. The deal calls for Avigen to manufacture the product for worldwide distribution. (See BioWorld Today, Nov. 20, 2000.)