Surprise Approval for Avastin

The FDA approval of the breast cancer treatment, which was opposed by advisory panels, shocked patients, doctors, and investors

by Catherine Arnst

When the Food & Drug Administration announced late on Feb. 22 that it had swept aside the objections of its expert advisers and approved Genentech's (DNA) Avastin for breast cancer, investors, patients, and cancer specialists were all caught off guard. The agency rarely goes against the recommendations of its outside advisory panels. The surprising decision set off a new round of speculation about the fate of another cancer drug—Provenge, a controversial prostate cancer treatment from Seattle-based Dendreon (DNDN) that was rejected by the FDA last May, even though an advisory committee determined that the drug was both safe and effective.

Investors hope the Avastin decision heralds a more flexible FDA that will look favorably on Provenge and other cancer drugs in the future. Indeed, Dendreon's stock (BusinessWeek, 6/4/07) inched up on Feb. 25, from 5.29 a share to as high as 5.62, before sinking back to 5.39. But close observers of the agency warn against such conclusions.

Avastin, which blocks blood vessel growth to the tumor, had several points in its favor in navigating the approval process: It has been on the market for some three years for colon and lung cancer, it is already approved in Europe for breast cancer, and it is frequently prescribed off-label for breast cancer in the U.S. That track record in other cancers made it easier to overlook Avastin's advisory panel, which voted 5-4 against approval because the drug shrank tumors but did not lead to longer life or improved quality of life for cancer patients.

Provenge Approval Eagerly Sought

No such advantages exist for Provenge, a radically new concept in cancer treatment. It is a vaccine that trains the body's own immune system to attack tumors, preventing them from recurring or spreading after initial treatment. As yet, no cancer vaccine has won approval anywhere in the world, in part because such vaccines can be devilishly hard to evaluate. Provenge, for example, failed to shrink tumors in the 127-patient trial presented to the FDA last year, a standard measure of efficacy. But patients on Provenge did live 4.5 months longer than those on standard treatment, with few significant side effects.

Since no new drugs for advanced prostate cancer have been introduced in more than 20 years, oncologists and patients alike are eager to see Provenge approved. The advisory committee voted 17-0 that the drug was safe and 13-4 that it was effective.

But FDA staffers wanted more and better data, out of concern that the survival benefit may have been a statistical fluke, which isn't uncommon in such small clinical trials. The FDA refused to approve the drug until it sees the results of another clinical trial, which won't be completed until later this year. "The FDA is like your parents, they do what they want and they are always right, regardless of how the advisory committees vote," says Dr. Mark Monane, a biotech analyst with Needham & Co. "They just didn't feel comfortable with the safety and efficacy of Provenge."

FDA Criticized by Cancer Patients

The FDA's Avastin decision was probably designed to reflect the agency's flexibility when it comes to cancer drugs, suggests analyst Dr. Gregory Frykman of Stanford Group, in a written analysis of the decision.

Cancer patient activists have roundly attacked the agency (BusinessWeek.com, 7/30/07) since the Provenge decision, arguing that the FDA is hindering the development of new treatments for deathly ill patients. Adding fuel to their protests is the FDA's failure to approve any new cancer drugs last year. Frykman suggests some staffers inside the agency may agree the FDA is being too cautious on cancer drugs.

But the agency did not give in completely to the will of its critics. The FDA gave Avastin only a conditional approval for metastatic breast cancer, the most advanced stage, and that go-ahead can be withdrawn if Genentech doesn't provide further data showing the drug's effectiveness against the disease. The agency did the same thing several years ago with Iressa, an AstraZeneca (AZN) drug for lung cancer whose clinical trial results were also far from definitive. Despite a big buildup and high expectations for the drug, follow-up trials failed to prove that Iressa was effective and the company stopped marketing it at the FDA's urging.

Dendreon might be better off waiting for all the data to come in.

Arnst is a senior writer for BusinessWeek based in New York.