Staff Writer

As if the news for Avastin couldn't get any better, Genentech Inc.'s stock swelled another 18.3 percent following the release of positive survival data in a third indication, breast cancer.

Shares (NYSE:DNA) rose $10.72 Friday to close at $69.35.

Genentech and partner F. Hoffmann La-Roche Ltd., of Basel, Switzerland, said an interim analysis of a Phase III study in first-line metastatic breast cancer showed Avastin (bevacizumab) plus paclitaxel improved progression-free survival when compared with chemotherapy alone. By meeting the primary efficacy endpoint, Avastin becomes a potential life-extending product for three different cancer indications: colorectal, non-small-cell lung, and now breast.

"Obviously, we haven't seen safety data, but this probably moves the market size up by 50 percent from the previous estimates," said Winton Gibbons, an analyst with Chicago-based William Blair & Co. LLC.

Breast cancer is another big money indication for Avastin. Colorectal, lung and breast cancer could carry the product's revenues to more than $3 billion, with $1 billion coming from each of the three indications. But that is a conservative estimate, Gibbons told BioWorld Today, and many analysts believe the breast cancer indication could double the market potential to about $4 billion.

The American Cancer Society estimates that 211,240 women will be diagnosed with breast cancer and 40,000 will die of the disease in the U.S. this year.

Colleen Wilson, spokeswoman for Genentech, said the company has not given guidance as to when it expects to file a supplemental biologics license application. The company does plan to meet with the FDA to discuss a filing for breast cancer, but the positive Phase III survival data came earlier than expected, during an interim analysis and not the final analysis.

"We had been assuming the final data would be available late this year or early next year," Wilson said.

Avastin binds to vascular endothelial growth factor and is designed to interfere with the blood supply to tumors. South San Francisco-based Genentech gained FDA approval for the product last year for first-line metastatic colorectal cancer. Pivotal data showed that patient survival increased with Avastin plus a chemotherapy combination of 5-FU, leucovorin and irinotecan by 4.7 months, compared with chemotherapy alone. Sales of the product reached $555 million in 2004, and $202.9 million in the first quarter of this year. (See BioWorld Today, Feb. 7, 2004.)

Data from the Phase III lung cancer trial showed Avastin plus paclitaxel and carboplatin improved survival in first-line non-squamous NSCLC by 2.3 months, or 23 percent, over chemotherapy alone. (See BioWorld Today, March 16, 2005.)

The Phase III breast cancer trial enrolled 722 women with untreated metastatic disease. They were randomized to receive paclitaxel with or without Avastin. The study did not include women with HER2-positive metastatic breast cancer unless they had received prior treatment with Herceptin (trastuzumab) or could not take Herceptin, Genentech's breast cancer product approved in 1998. Detailed results from the Phase III trial will be presented at an upcoming medical meeting.

The Herceptin and Avastin markets should not overlap, since Herceptin treats first-line metastatic breast cancer that overexpresses the HER2 protein, and Avastin would treat the 75 percent of breast cancer patients that are not HER2-positive, Wilson said. The company is conducting some early Phase I/II trials evaluating the use of the two products together.

The Phase III breast cancer study of Avastin also excluded patients who had received adjuvant paclitaxel within the previous 12 months and those with a history of blood clots or who were receiving blood thinners.

While the analysis of safety data is not complete, adverse events appear to be similar to those seen in previous trials. Patients in the Avastin arm experienced neuropathy, hypertension and proteinuria more often than patients in the control arm. There were rare cases of serious bleeding and blood clots, but other adverse events were similar between the two treatment arms.

The National Cancer Institute sponsored the trial under a cooperative research and development agreement with Genentech. It was conducted by a network of researchers led by the Eastern Cooperative Oncology Group.

Last fall, analysts scaled back their models of Avastin for colorectal cancer and seemed disappointed with sales figures recorded for the year. They believed that growth of the product was flattening earlier than expected, and they stressed the importance of expanding the product into additional indications.

"Now with positive data in lung and breast cancers, you might get people starting to think more expansively, and think it's going to be used in most solid tumors," Gibbons said.

With sBLAs being prepared for NSCLC and breast cancer, the clinical focus for Avastin is on Phase III trials in adjuvant and metastatic colorectal, renal-cell, pancreatic, ovarian and prostate cancers. All of the trials are still enrolling patients, Wilson said. The most near-term Avastin data would come from a Phase II trial evaluating the product's use with Tarceva in kidney cancer.

The next horizon for Genentech might be the Phase III data for Lucentis in age-related macular degeneration. The product is a potential competitor of Macugen (Pfizer Inc. and Eyetech Pharmaceuticals Inc.).

"Our expectation is the Lucentis data will be as good and likely better than the Macugen data," Gibbons said. "So that could be another positive mid-year catalyst for the company."

Published  April 18, 2005