In a controversial 2008 decision, the FDA gave a fast-track approval for the pricey drug Avastin for breast cancer treatment based on a single study. Now, after subsequent research proved disappointing, the agency is moving to revoke the approval, angering patients and the drug's maker.
Callous bureaucrats are trying to steal away their hope. That's the way several dozen protesters outside the Food and Drug Administration's headquarters yesterday saw it.
Inside another 20 breast cancer patients and their supporters stepped up to microphones to plead with the agency, sometimes tearfully, not to withdraw approval of Avastin, an $88,000-a-year drug they're convinced has prolonged their lives.
In a controversial 2008 decision, the agency gave a fast-track approval for the pricey drug for breast cancer treatment based on a single study, but Genentech, the San Francisco-based maker of Avastin, was required to continue research on the drug.
Subsequent results were disappointing, and the FDA has moved to revoke the approval for breast cancer. The public hearing was triggered by Genentech's appeal of the agency's decision.
Many women who say the medicine helped them testified in favor of the drug. "I have been on Avastin for three years this month and have had 32 months of no (cancer) progression," said Christi Turnage, a nurse and mother of four. "That is priceless."
It's a tough position for regulators to be in. And in the past, the FDA has sometimes yielded to such pressure.
But in the first of two days of hearings, FDA staffers held firm to their conclusion that Avastin shouldn't be used any longer to treat advanced breast cancer.
Many patients and cancer specialists worry that if the FDA sticks to its guns, insurers won't pay the high cost of Avastin treatment. But that's not so clear. "I'm not certain an insurer would want to fight this coverage battle in the current environment," Dr. Len Lichtenfeld of the American Cancer Society told the Wall Street Journal.
The Avastin situation is a classic case of data versus anecdote. "We are aware of the human toll caused by breast cancer," said Dr. Richard Pazdur, chief of the FDA's cancer drug unit, who had earlier been booed by the protesters. "We are aware that some patients and physicians believe Avastin has provided benefit."
But, he added, "the total of evidence points very clearly to the conclusion that Avastin has not been shown to be safe or effective" for breast cancer treatment.
One FDA official says Avastin's "accelerated approval" three years ago was "a close call." It was based on a study that didn't show the drug prolonged the lives of patients with metastatic breast cancer. But it did extend by about five months their "progression-free" survival — the time without detectable new tumor growth.
But as a condition of approval, the FDA asked Genentech, a unit of Roche, to do more studies to verify the first one — and hopefully buttress the decision with data showing improved quality of life or even extends patients' lives — the gold standard of cancer drug efficacy.
Alas, the followup studies neither verified the first study nor provided new reasons to maintain Avastin's approval for treating breast cancer. The typical Avastin-user in these studies had only a month or so of additional progression-free survival, compared to conventional treatment. And the drug carries side effects, some of them severe.
"Despite the hopes of everyone inside and outside this room," said Dr. Patricia Keegan of the FDA, "after conducting three trials enrolling more than 2,400 women ... there is no evidence that Avastin saves or extends lives."
Keegan took the unusual step of answering the emotional testimony from Avastin users. "This morning we have heard from patients and their families who feel how they have benefited," she said. "But there are other voices that need to be heard. Those voices include a 53-year-old woman with metastatic breast cancer who suffered severe abdominal pain caused by gastrointestinal perforation that led to her death after four doses of Avastin."
Serious side effects were twice as high among Avastin-users in one study. Severe or life-threatening high blood pressure was five times higher.
A Genentech spokesman, Ed Lang, countered that side effects are real and important, "but you also saw examples this morning of women who are living" because of Avastin.
The company, which sells about a billion dollars' worth of Avastin to treat breast cancer, wants the FDA to maintain its approval of the drug for this disease while it mounts another study that, it hopes, will provide the kind of justification the FDA is seeking.
Avastin is also approved to treat kidney cancer, lung cancer, brain cancer and colorectal cancer. Its use for these diseases is not at issue in this week's hearing.
Genentech also seeks to establish a very high bar for FDA to withdraw a drug that's gotten accelerated approval. The company proposes to allow withdrawal only if "there is no reasonable likelihood of clinical benefit and no possibility that additional study might further characterize any existing benefit."
But Dr. John Jenkins, head of the FDA's Office of New Drugs, says Genentech's criteria "would turn the accelerated acceptance program on its head, allowing protracted marketing of drugs that have not been shown to be safe and effective while sponsors take numerous bites of the apple in an effort to confirm clinical benefit."
FDA officials note that Genentech's proposed new study won't produce results for several years. It hasn't even been designed yet. Clearly, the FDA sees this as a test case for its ability to withdraw conditional approval of a drug if it doesn't pass muster in followup studies.
Put simply, the case poses the question: "Do data matter?"
Whatever the outcome, it will be precedent-setting. It's the first time a drug company has challenged the FDA's authority to withdraw a drug after it has won accelerated approval. Among nearly 50 other cancer drugs approved through this mechanism, most have stood the test of time. And when they haven't, their makers have voluntarily withdrawn them.
Today the FDA's Oncologic Drug Advisory Committee is expected to vote on the question. A year ago that panel voted 12 to 1 to withdraw Avastin for breast cancer treatment, and last December the FDA announced its decision to do so, triggering this week's appeal by Genentech.
The final decision rests with FDA Commissioner Margaret Hamburg.