By Randall Osborne

Genentech Inc. reported encouraging preliminary results from Phase III trials of Herceptin (trastuzumab), its monoclonal antibody against an especially aggressive form of breast cancer that affects up to one-third of patients.

"We're going to file a biologics license application [BLA] with the FDA in the second quarter, which is a very aggressive time frame," said Laura Leber, spokesperson for South San Francisco-based Genentech. "This is an enormous amount of data."

Meanwhile, Genentech will continue its analysis of the Phase III data, and will begin more trials in the spring. The company also plans to make more of the drug available to severely ill patients as part of a separate open-label safety trial.

"For about two years, we've given it out to 25 patients per quarter," Leber said. "In February, we're increasing that to 100 per quarter." Patients who receive the drug are chosen by lottery.

In the Phase III trials, Herceptin was studied against metastatic cancer in patients known to overexpress the HER2 oncogene. The drug, a humanized HER2 antibody, binds to the HER2 growth factor receptors, which are present in excessive numbers on the surfaces of cancer cells. Since those receptors cause the cells to multiply faster than others, neutralizing their function could slow a tumor's growth.

A randomized, controlled Phase III trial evaluated the safety and efficacy of Herceptin in 469 women undergoing chemotherapy regimens — paclitaxel or anthracycline plus cyclophosphamide — as compared with treatment with either of those regimens alone. The patients, whose cancers metastasized, had not previously been treated with chemotherapy.

Detailed results will be presented later, but preliminary analysis of the data showed patients received clinical benefit from Herceptin, which slowed the cancer's progress and shrank tumor size. Further review will be made of those factors, along with other factors, such as response duration, time to treatment failure, quality of life and survival.

The most common adverse events were infusion-related chills and fever. However, some women treated with Herceptin and anthracyclines showed a greater risk of cardiac dysfunction than those treated with anthracyclines alone. A limited number of patients treated with Herceptin and paclitaxel, or Herceptin alone, did not show a large increased cardiac risk.

A second trial studied Herceptin as a single agent in 222 women with metastatic breast cancer in whom the HER2 was overexpressed. These patients, who had relapsed after one or two chemotherapy treatments, also showed clinical benefit.

"The parameters were much different," Leber said. "These folks are not doing well, and the primary endpoint was response rate, so the results will be different." Data from the second Phase III trial, along with a more detailed analysis of data from the first, will be made public later, Leber said.

Genentech's stock (NYSE:GNE) closed Monday at $58.875, unchanged. *