FDA Asks For More Data On Genentech's Avastin

The Food and Drug Administration wants more information before it decides whether to approve Genentech Inc.'s (DNA) blockbuster drug Avastin as a treatment for advanced breast cancer, the biotechnology company said Monday. The request will probably delay final FDA action until late 2007. Recent approvals

Genentech originally hoped to begin marketing the drug as a treatment for advanced breast cancer by early 2007, assuming the use was approved; Avastin currently is approved for colorectal-cancer treatment. Now, following an FDA request for additional safety and efficacy data, Genentech said it expects to resubmit its application by mid-2007, and an FDA review would likely take an additional six months.

Genentech, of South San Francisco, Calif., has indicated that FDA approval for new uses of Avastin such as breast cancer treatment could help boost the drug's price by about two-thirds - to nearly $90,000 per patient annually - because some uses require twice as much of the drug as in colorectal cancer.

News of the regulatory setback sent Genentech shares down $4.37, or 5.3%, to $77.70 on Monday on volume of 7.5 million. The daily average volume is 2.8 million shares.

"We view today's announcement as a minor setback to Genentech but remain optimistic about Avastin's prospects in breast cancer," Bank of America analyst David Witzke wrote in a research note. "In our opinion the delay has the potential to push out the FDA approval one year."

Hal Barron, senior vice president of development and chief medical officer, said in a Genentech press release the company was disappointed in the delay, "as there is a great unmet medical need for women with metastatic breast cancer."

Avastin was approved by the FDA in February 2004 as a treatment for colorectal cancer in combination with chemotherapy, and has quickly become a big seller. Last year, Avastin generated U.S. sales of $1.13 billion, more than double the year before. Swiss drug company Roche Holding AG (RHHBY), which owns a majority of Genentech, markets Avastin outside the U.S.

Some of Avastin's sales growth has come from unapproved uses such as treating breast cancer and an eye disease. Genentech is studying Avastin in several additional tumor types, including lung, prostate and kidney cancers. Avastin is designed to work by starving tumors of vital nutrients.

In May, Genentech applied for FDA approval of Avastin in combination with chemotherapy to treat metastatic breast cancer, or cancer that has spread to other parts of the body. The FDA granted the application priority-review status, which means it shortened its expected review period to six months from 10 months.

The application in May was based on interim data from a trial that showed women with advanced breast cancer who took Avastin plus chemotherapy had progression-free survival of more than a year, compared with six months for women on chemotherapy alone. Progression-free survival is the time from the start of treatment until tumor growth or death.

The FDA has requested a "substantial safety and efficacy update" from the trial, including an independent review of radiographic scans of patients to measure progression-free survival.

The study in question was sponsored by the National Cancer Institute, a government research institute, under an agreement with Genentech, which supplied the medication. Researchers in the study were led by the Eastern Cooperative Oncology Group, a clinical-research organization based in Philadelphia.

Genentech said Monday the FDA is now requesting that the data from the trial be audited and summarized "in a manner typically used for a company-sponsored trial." Genentech said that request was different from its understanding of the FDA's approach when it first submitted the application. Genentech said the request would require the recollection of data from study sites.

Cooperative-group studies typically don't have independent verifications of radiographic scans, Robert Mass, a medical director at Genentech, said in an interview. Such independent reviews are typically required only of company-sponsored trials, he said.

The FDA appears to have decided that cooperative-group studies need to be analyzed much more like industry-sponsored trials, said Gwen Fyfe, vice president of the clinical group at Genentech.

The FDA also wanted additional safety data, the executives said. The study submitted to the FDA in May showed that adverse events were similar to previous trials of Avastin plus chemotherapy and included hypertension and neuropathy, which involves nerve problems.

"This is certainly a negative surprise and bad for sentiment, especially as this is the second setback for the drug this year, but it's not the end of the world for Avastin," said Tilman Dumrese, an analyst in Zurich with private bank Sal. Oppenheim, who covers Roche. In late June, researchers stopped a trial investigating Avastin's potential in pancreatic cancer, after the drug failed to prolong the lives of these patients.