AVI BioPharma Inc. changed the course for its lead anticancer product, the vaccine Avicine, in an effort to shorten the route toward a possible FDA approval.

The Portland, Ore.-based company plans to initiate a Phase III trial for Avicine in pancreatic cancer. CEO Denis Burger said the FDA now often expects to have two studies for all new cancer drugs, including a pivotal Phase III and a supporting Phase I/II. Therefore, AVI BioPharma will use its ongoing Phase III trial in colorectal cancer as the supporting trial and the Phase III in pancreatic cancer as the lead.

“There are two things that influenced the strategy,” Burger told BioWorld Today. “One, it is the fastest route to the approval pathway. Also, we had very strong Phase II data in pancreatic cancer.”

Avicine is a therapeutic vaccine that blocks human chorionic gonadotropin, which acts to facilitate tumor growth, angiogenesis and immunosuppression, the company said.

The Phase III trial in pancreatic cancer will be conducted with AVI’s marketing and co-development partner, SuperGen Inc., of San Ramon, Calif. (See BioWorld Today, April 6, 2000.)

The trial is expected to take less time to complete than the ongoing Phase III trial in colorectal cancer, which began in January 2001. (See BioWorld Today, Jan. 5, 2001.)

At this point, Burger said the Phase III in pancreatic cancer would likely take three years. It will involve 600 patients in total, and it will take at least a year to enroll them. One-third of the patients will treated with Avicine alone; one-third will be treated with gemcitabine, or Eli Lilly and Co.’s Gemzar; and the final third will be treated with a combination of Avicine and Gemzar.

The primary endpoints will be median survival and one-year survival.

One of the important features of this trial design, Burger said, is the fact that one group will be treated only with Avicine.

“Usually, going into first-line therapy, you are not able to use a new drug on its own, so you have to use it in combination with the best common care,” he said. “But because pancreatic cancer is such a devastating disease and because Gemzar doesn’t offer a huge benefit and is a drug with well-defined toxicities, we have the opportunity to use the vaccine on its own.”

What that provides AVI is two routes to reach approval conclusions from the trial. Pancreatic cancer when untreated has a 16-week median survival period. With Gemzar treatment, the median survival time increases to 23 weeks, Burger said.

“With the vaccine alone, if we achieved the same survival, we have the potential to be approvable because it avoids the chemotherapy toxicities related to Gemzar, because there would be a quality-of-life benefit without the side effects,” Burger said.

Secondly, there is the possibility of approval in combination with Gemzar, based on the positive results from the Phase II trial in pancreatic cancer. The second important endpoint would be survival at one year, which is possible because the Phase II trial in pancreatic showed survival at that period doubled, he said.

The Phase II trial in pancreatic cancer was a randomized, multicenter study. The one-year survival rate for the group treated with Avicine alone was 15 percent. The one-year survival rate was about 30 percent for those treated with Gemzar and Avicine, compared with the survival rate of 15 percent to 18 percent as published on Gemzar’s package insert, Burger said.

“I think everyone in the cancer community thinks that combination therapies have the best chance,” Burger said.

The most common side effect of the Avicine vaccine is a mild reaction at the injection site, the company said.

Avicine is AVI’s lead candidate in its cancer immunotherapy platform. It also has the Neugene antisense drug program, with the lead product, Resten-NG, designed to treat cancer, cardiovascular restenosis and other cell proliferation disorders by inhibiting the production of a cellular transcription factor, the oncogene c-myc. Resten-NG is in a Phase I/II for cancer and polycystic kidney disease and in Phase II trials for restenosis.

In late March, the company closed a private equity financing of about $22 million, thereby gaining an additional year of cash to fund ongoing clinical trials and operations. Alan Timmins, president and chief operating officer, said at the time that the company had about two years of cash. (See BioWorld Today, March 27, 2002.)

AVI’s stock (NASDAQ:AVII) fell 10 cents Thursday to close at $7.44.