By Lisa Seachrist

Washington Editor

WASHINGTON — Designated a fast-track drug in May, Genentech Inc.'s Herceptin, a monoclonal antibody designed to combat certain forms of breast cancer, is scheduled to be the subject of review by the FDA's Oncology Drugs Advisory Committee today.

In assessing the merits of Herceptin, the committee will be reviewing the first therapy aimed at the underlying molecular mechanisms of cancer.

"The big news is that this is the first time a product has been designed against an underlying defect in a cancer cell," said Susan Hellmann, senior vice president and chief medical officer for the South San Francisco-based firm. "It really seems to bring to fruition the promise of biotechnology."

Herceptin is a humanized monoclonal antibody against the growth factor receptor HER2. Approximately one-third of all breast cancers overexpress the HER2 gene, littering the surface of the cells with receptors that fuel the growth of cancer. As a result, breast tumors which overexpress HER2 are especially aggressive.

The drug does not kill breast cancer cells. Instead, it neutralizes the activity of the receptors and slows tumor growth.

In presenting the drug to the advisory panel, Genentech will rely on two clinical trials testing Herceptin in patients with metastatic breast cancer that overexpressed HER2.

The Phase III study included 469 women and pitted Herceptin in combination with standard chemotherapy agents against the chemotherapy regimens alone. Patients received an infusion of Herceptin at 4 milligrams per kilogram on the first day of treatment, and then a weekly dose of 2 milligrams per kilogram for the length of the study.

Patients who received Herceptin in addition to the standard chemotherapy experienced tumor progression later than patients receiving the chemotherapy alone. Overall, Herceptin slowed the median time to disease progression by 65 percent (from 4.6 months to 7.6 months). Twenty-eight percent of patients who received Herceptin had no signs of tumor growth at one year, compared to 14 percent of patients who received only the chemotherapy. And Herceptin raised the response rate by 53 percent over the chemotherapy alone.

Herceptin Is Not Without Side Effects

A second trial, in 222 women with metastatic breast cancer who had failed prior chemotherapy, tested Herceptin as a single agent. All women in this trial received Herceptin. Overall, the response rate was 16 percent, with four patients having a complete response while 26 patients had a partial response. The median duration of the response was nine months.

Hellmann noted that, in addition to slowing tumor progression, Herceptin is a well-tolerated drug that doesn't cause chemotherapy-associated side effects like hair loss and nausea. However, Herceptin does cause side effects.

She said about 40 percent of the patients experienced infusion reactions consisting of chills and fever. These reactions usually occurred during the first infusion and most were treated with acetaminophen.

Herceptin also raised the incidence of cardiac dysfunction, characterized as heart failure, especially in patients treated with anthracycline and cyclophosphamide (AC). Anthracyclines are known to cause heart failure. However, only 7 percent of the patients receiving AC therapy experienced heart failure, compared to 28 percent of the patients receiving Herceptin plus anthracycline therapy. Eleven percent of patients receiving Herceptin and paclitaxel experienced heart failure, compared to 1 percent receiving paclitaxel alone. The cardiac dysfunction was responsive to standard cardiac medicines.

"This is a really robust data set," Hellmann said. "We have a good idea of both the risks and the benefits of this drug."

Genentech is seeking a label for Herceptin that is consistent with its clinical trials as a treatment for patients with metastatic breast cancer. Hellmann said that the company is currently discussing a clinical program to test the drug as a treatment for HER2-positive breast cancer that has not yet spread.

FDA Decision Could Come By November

The company also is exploring whether HER2 overexpression is common in ovarian, prostate, lung and colon cancers, and whether testing Herceptin in these cancers makes sense.

"We are beginning to move toward the day when we treat a cancer based on its genetics rather than the organ it arises in," Hellmann said. "It's exciting because this really is the promise of biotechnology. We've a lot of work left to do, but I hope that we are on the brink of something incredible."

Today's advisory panel meeting is the first step toward approval. Because Herceptin is a fast-track drug receiving priority review, an FDA decision could come by November.

Genentech's stock (NYSE:GNE) closed Tuesday at $65, down $1.125. *