By Debbie Strickland

Biomira Inc. and marketing partner Chiron Corp. are nearing the launch of a Phase III international trial of Theratope therapeutic vaccine. The trial, expected to begin by early 1998, will be conducted in North America and Europe in women with metastatic breast cancer who have responded to first-line chemotherapy.

"The FDA accepts in principle our plans for moving into Phase III," said Alex McPherson, Biomira's president and CEO, following a meeting with officials from the agency's Center for Biologics Evaluation and Research.

"There has been enthusiastic reception of the trial design and also enthusiasm for the fact that this is a survival study," reported Grant MacLean, the company's vice president for clinical and regulatory affairs. "Other studies look at response rates and try to argue that response rates may correlate with survival, although that's never been demonstrated . . . We're actually looking at survival, which is what the physicians and patients are most interested in."

Based in Edmonton, Alberta, Biomira calls Theratope its flagship product. The vaccine has thus far been tested in more than 300 patients in Canada, the U.S. and the U.K.

Theratope is a synthetic, carbohydrate-based vaccine designed to stimulate a patient's own immune system to control cancer with minimal side effects. If it wins FDA approval, it will be marketed by Chiron Therapeutics, the Emeryville, Calif., company's cancer drug marketing subsidiary, and will join a line-up of cancer products that includes Aredia for the treatment of bone metastases associated with breast cancer, and Proleukin for metastatic kidney cancer.

In the Phase III trial plans under discussion, Theratope-treated patients would receive an administration of the vaccine following a pretreatment of low-dose intravenous cyclophosphamide. All patients will have received a conventional, six-month course of chemotherapy.

Data To Be Analyzed In One Year

The proposed double-blind, prospectively randomized study will enroll 950 patients over the course of 18 months, with a goal of gaining 900 evaluable patients. Researchers will investigate whether the vaccine can delay disease progression and increase patient survival in a large patient population. The trial's design will allow for an early analysis within a year of patient accrual, comparing time to disease progression between patients randomized to treatment with Theratope and patients randomized to a placebo vaccine.

Should this early analysis show that time to disease progression in the group treated with Theratope is clearly greater than that observed in the placebo group, Biomira and Chiron will seek marketing clearance under the accelerated approval process.

The FDA could become the first regulatory agency to grant approval of Theratope, if the trial goes well.

"Our strategy is to move as quickly as possible with the FDA," said MacLean. "They've been very cooperative on this. They also would like to see this product move quickly."

Regulators in the U.K. have also been very supportive, he added.

Phase II Trials Conducted In The U.K. And Canada

In the Phase II trial, also conducted with metastatic breast cancer patients, the drug boosted survival for 25 patients to a median of 26.5 months, a statistically significant improvement over the control group's 9.2 months. Control patients received conventional therapies and were selected from the National Oncology Database.

Biomira has further reported a correlation between the strength of antibody response to Theratope and increased survival in 125 cancer patients with breast, colorectal, ovarian or pancreatic cancer.

"It does what it's supposed to do," MacLean said. "It produces an immune response not only to the vaccine but to the relevant cancer-associated antigens, and it appears to increase survival."

Under terms of an agreement inked in May, Chiron and Biomira will share equally U.S. and European research and development costs, as well as clinical and regulatory costs. Biomira received an up-front fee of $1.4 million and will receive other milestones as the therapeutic vaccine progresses toward commercialization.

Full financial details of the collaboration have not been disclosed, although Biomira in its second-quarter report said the revenue-sharing component of the deal is "better than industry norms, which are generally based on a 60:40 percent partnership between the sales, marketing and distribution partner and the manufacturing partner respectively."

A joint management committee, comprising representatives from each company, is overseeing development of Theratope indications in the U.S. and Europe. In addition to metastatic breast cancer, a condition affecting about 50,000 to 65,000 patients in the U.S., the companies are investigating Theratope's potential for treating metastatic ovarian and colon cancers.

Theratope is 12-year-old Biomira's most advanced therapeutic candidate, and is undergoing trials for ovarian and colorectal cancer in addition to the lead indication of metastatic breast cancer.

For the quarter ending June 30, the company reported revenues of C$4.0 million, up from C$2.3 million for the corresponding period in 1996. The company's net loss was C$8.6 million. Biomira finished the quarter with C$85.88 million in cash.

Biomira's shares (NASDAQ:BIOMF) closed Thursday at $4.468, down $0.94. Chiron's stock (NASDAQ:CHIR) lost $0.125 to end the day at $22. *