By Randall Osborne

West Coast Editor

Walloped by the market in April when the company put its cancer-vaccine trials on clinical hold after the FDA sought further information, Avax Technologies Inc. got somewhat more bad news, disclosing Friday that the agency is not satisfied yet.

¿I don¿t think there¿s even been a clinical hold where the first response has been enough for the FDA,¿ said David Tousley, chief operating officer of Kansas City, Mo.-based Avax. ¿That¿s just the reality of it.¿

Avax¿s shares (NASDAQ:AVXT) closed Friday at $1.13, up 9 cents. The earlier news had pushed the stock down 43 percent.

The company¿s response to the first agency queries ¿was so voluminous that it was likely they were going to have more questions,¿ Tousley added.

Also in April, two company officials resigned at the request of the board of directors ¿ CEO Jeffrey Jonas had resigned in February ¿ and Avax said the FDA would inspect its manufacturing facility in Philadelphia, while the company conducted its own internal review. (See BioWorld Today, April 24, 2001.)

Avax makes cancer vaccines M-Vax for melanoma and O-Vax for ovarian cancer by using the patient¿s own cells, which are modified with a hapten molecule so that the tumor cells appear foreign to the body, and are attacked by the immune system.

¿It¿s a sterility issue, the sterility of tumors coming in [to the manufacturing facility],¿ Tousley told BioWorld Today. ¿In the trials that were under way, in the melanoma trial, we had up to 25 sites around the country, and about 17 for ovarian.¿

When the FDA gives its nod, stricter guidelines for handling samples will be in place, he said.

¿I would not point the finger at the hospitals,¿ he said. ¿They do what they have to do. But we¿ve now validated our aseptic process within the facility. We know we won¿t be introducing contaminants.¿

Where the contamination might have entered ¿really doesn¿t matter,¿ Tousley said. ¿We have to clean up the whole thing.¿

Avax expects to respond to the FDA¿s new concerns within two weeks. Then, the FDA gets another 30 days to review the response ¿ after which it may ask for still more information, and could demand a meeting with the company before the clinical hold is ended.

Meanwhile, Avax is continuing to develop its process.

¿[Hospitals] ship tumor to us by Fed Ex, on ice in a special container,¿ Tousley said. ¿It looks like a Styrofoam beer cooler, with gel packs and a little container the tumor goes into, and saline solution.¿

The tumor is used to make the vaccine, which is shipped dose by dose in vials to the physician¿s office, with an 18-hour window between manufacture and injection.

¿There hasn¿t been an instance where the dose hasn¿t gotten into the patient,¿ Tousley said, noting that even a hurricane in Florida did not deter the dosing.

¿This isn¿t a pediatric vaccine or pills for hair loss,¿ he said. ¿When a cancer patient makes an appointment, they¿re going to be there.¿

As long as the drug also is there, everything works fine. But the scheduling might make prospective pharmaceutical partners think twice, and Avax has been working on changes ¿ specifically, on freezing batches of the vaccine.

¿Freezing allows us to make all of the vaccine at one time,¿ Tousley said, so that it¿s ¿akin to an off-the-shelf product.¿

FDA guidelines with regard to cancer vaccines and autologous cell therapy are evolving, Tousley said.

¿Within the last year and a half, there was an FDA-sponsored meeting to get all the cancer vaccines to talk about characterizations of them,¿ he said. ¿You can¿t look at these the way you would look at a small-molecule drug.¿

Even determining whether a trial is Phase II or Phase III is difficult, Tousley said. Avax views the results with the two vaccines as encouraging: a 50 percent to 60 percent immune response in melanoma patients, with a five-year survival rate of as much as 60 percent, and positive data from ovarian studies.

Although progress has been made in fixing sterility glitches, the FDA will have the final word, Tousley said.

Avax, meanwhile, is doing all it can to line up data and procedures as they agency wants them. ¿We hope to come out of this much stronger,¿ Tousley said.