By Kim Coghill

Washington Editor

AVI BioPharma Inc. said it has marked the final stage in development of its therapeutic cancer vaccine, Avicine, by entering Phase III clinical trials for the treatment of colorectal cancer.

In an 800-patient randomized study, participants will receive either Avicine in combination with chemotherapy, or chemotherapy alone.

"An important consideration here is that in our previous studies in colorectal cancer in a Phase II, 77-patient trial, we were dealing with patients in second-line therapy, so they had already failed chemotherapy," said Denis Burger, chairman and CEO of Portland, Ore.-based AVI. "In this study, based on good results from Phase II, we are in first-line therapy, so that means these are patients who have been diagnosed with some metastatic disease so they can't be cured by surgery alone. But they are chemo-naove, so a much better category of patients, and much more ideal for testing a therapeutic vaccine."

The vaccine is being tested for use on its own, and in conjunction with chemotherapy, Burger said.

Initially the trials will involve 10 to 20 cancer centers throughout the United States, with an expected expansion.

Burger would not say when he expects the trials to be complete, but did say enrollment should proceed at a reasonable rate due to the availability of study patients. Colorectal cancer is the third most frequently occurring cancer type in the U.S., with approximately 130,200 diagnoses and 56,300 deaths in 2000.

In the Phase III trial, Burger said the median survival rate of patients treated with chemotherapy alone is expected to be 11 months, and individuals treated with the combination are expected to live longer.

And per FDA regulations for cancer products, the study's primary endpoint is survival, while the secondary endpoint is time to disease progression.

Avicine is a non-toxic therapeutic cancer vaccine that elicits a highly specific immune response to human chorionic gonadotropin (hCG), a cancer-associated oncofetal protein. The vaccine blocks hCG's function, which is to facilitate tumor growth, angiogenesis, invasion and immunosuppression.

Avicine was developed by ImmunoTherapy Corp., a Seattle-based cancer vaccine specialist, which in November 1997 merged with AntiVirals Inc. in a deal worth about $24 million to become AVI BioPharma. (See BioWorld Today, Nov. 7, 1997.)

AVI has licensed the sales and marketing rights in the U.S. to SuperGen Inc., of San Ramon, Calif. The companies will share equally in the clinical trial and regulatory costs of Avicine development, and will share equally in U.S. profits.

AVI also is testing Avicine in pancreatic cancer patients. The company recently completed enrollment for a 50-patient, multicenter Phase II randomized trial to evaluate the safety and efficacy of Avicine alone compared to the drug in combination with gemcitabine (Gemsar) produced by Eli Lilly & Co., of Indianapolis. Data are expected mid-year.

In late December, AVI completed preclinical studies using its Neugene antisense technology targeting the liver enzyme cytochrome P450. The studies indicated that Neugenes would alter expression of cytochrome P450 3A4 (CYP 3A4) in the liver. CYP 3A4 is a liver enzyme that regulates metabolism of about 60 percent of all FDA-approved drugs and drugs broken down by this enzyme stayed in an active form longer.

AVI also recently completed oral delivery studies in a Phase I human trial of its Neugene antisense drug designed to inhibit cardiovascular restenosis, cancer and polycystic kidney diseases. AVI is in a Phase II clinical trial with the drug for the same indication.

AVI's stock (NASDAQ:AVII) closed Thursday at $5.312, up 18.75 cents.