By Mary Welch

AVI BioPharma Inc. will start Phase III trials with Avicine, a synthetic peptide conjugate vaccine, as first-line treatment of colorectal cancer in combination with chemotherapy.

"We had a wonderful meeting on the Phase II data with the FDA and we've already had our meeting to finalize Phase III protocol with the FDA," said Denis Burger, AVI's president and CEO. "We've done three Phase I trials and two Phase II trials and now we're moving into Phase III. We're excited."

The Phase III trial will involve 500 patients who will receive chemotherapy with a placebo vaccine or with Avicine. Patients will have metastatic colorectal cancer but must be naove to chemotherapy. The trial will last two years with the endpoints being progression-free survival and survival, Burger said.

Formerly known as CTP-7, Avicine is a synthetic peptide conjugate vaccine designed to fight cancer by turning the immune system against cells that carry a hormone common to many tumor types: the human chorionic gonadotropin (hCG) hormone. HCG is a cancer-associated oncofetal protein, which boosts growth and shields cells from immune system attacks.

Essentially a nontoxic therapeutic cancer vaccine, Avicine elicits a highly specific immune response to the hCG by blocking the hormonal potentation of tumor growth, angiogenesis, invasion and immunosuppression.

"HCG is known as the pregnancy hormone," Burger explained. "It's what is detected in all those pregnancy tests. The placebo and fetus make those hormones. Men don't make it, obviously - except when they have cancer. It has been observed so far in a variety of cancers - lung, breast, pancreatic, among others."

According to Burger, the activity of hCG is well known.

"It stimulates fetal development and helps the fetus adhere to the uterine wall," he said. "It also provides immunosuppressive properties or else the body would reject the fetus. Our feeling is that this hormone does similar feats in malignancies. Even without a cancer trial, we know what the vaccine can do and its mechanism of action. It blocks the activity of this hormone which is protecting the cancer cells from immune recognition. So if you neutralize the function of that hormone, you can get an immune response against the tumor."

The Phase II trial data showed there were survival benefits in patients who showed immune responses to vaccination by the third month of therapy. In the Phase II trials, Avicine was used as a second-line therapy but will become a first-line treatment option in the Phase III trials. The company intends to release further information via peer-reviewed journals and a presentation at the May meeting of the American Society of Clinical Oncology.

Avicine also is in a Phase II trial in pancreatic cancer. Patients receive Avicine alone or Avicine in combination with gemcitabine, which is produced by Eli Lilly and Co., of Indianapolis. Of the 77 patients treated, about two-thirds produced antibodies to hCG, and median survival in that group was 42 weeks, compared to 17 weeks in those who did not produce specific antibodies.

And Avicine is in a Phase II trial in prostate cancer.

Avicine was developed by ImmunoTherapy Corp. (ITC), a Seattle-based cancer vaccine specialist. In November 1997, ITC merged with AntiVirals Inc. in a deal worth about $24 million. The name was later changed to AVI Biopharma. (See BioWorld Today, Nov. 7, 1997, p. 1.)

AVI BioPharma's stock (NASDAQ:AVII) closed Tuesday at $6.437, up 31.25 cents.