The commissioner of the Food and Drug Administration on Friday revoked the approval of the drug Avastin as a treatment for breast cancer, ruling on an emotional issue that pitted the hopes of some desperate patients against the statistics of clinical trials.
The commissioner, Dr. Margaret A. Hamburg, said that clinical trials had shown that the drug was not helping breast cancer patients to live longer or to meaningfully control their tumors, but did expose them to potentially serious side effects like severe high blood pressure and hemorrhaging.
“Sometimes, despite the hopes of investigators, patients, industry and even the F.D.A. itself, the results of rigorous testing can be disappointing,” Dr. Hamburg told reporters Friday. “This is the case with Avastin when used for the treatment of metastatic breast cancer.”
Avastin will remain on the market as a treatment for other types of cancers, so doctors can use it off-label for breast cancer. But insurers might no longer pay for the drug, which would put it out of reach of many women because it costs about $88,000 a year.
Federal officials said on Friday that Medicare would still provide coverage for the drug’s use in breast cancer, though the government plans to “monitor the issue and evaluate coverage options.”
The drug’s manufacturer, Genentech, which fought long and hard to retain the approval, said it was “disappointed.” The decision could cost Genentech and its Swiss parent company, Roche, up to $1 billion in annual sales. Use of Avastin has already declined to 20 percent, from 60 percent, of American patients with newly diagnosed metastatic breast cancer, the condition for which the drug was approved, according to Genentech. About 29,000 women each year are found to have metastatic breast cancer.
A Genentech spokeswoman said the company would continue to provide some help to breast cancer patients in securing insurance coverage. But it will no longer provide co-payment assistance and will no longer cap combined expenses for many patients and their insurers at $58,000 a year.
Dr. Hamburg’s decision, outlined in a 69-page memorandum, agrees with the unanimous recommendation made by an F.D.A. advisory committee in June, at the end of a two-day hearing at which some women taking the drug pleaded for its continued approval.
“I’m disappointed the commissioner has chosen to take the hardest line possible,” Terrence D. Kalley of Troy, Mich., whose wife, Arlene, has been taking Avastin, said Friday. Mr. Kalley, who organized a protest outside the F.D.A. hearing in June, said that for some women, Friday’s decision was “nothing short of a death sentence.”
The decision could also be grist for opponents of health care reform. Senator David Vitter, Republican of Louisiana, accused the F.D.A. on Friday of “rationing access” to treatment. The F.D.A. has insisted that cost issues were not considered. Yet some advocacy groups praised the decision. “It is the right decision for women and for science,” Frances M. Visco, president of the National Breast Cancer Coalition, said in an e-mail. “We all wished the drug worked. It does not.”
The administration has pledged to make decisions on the basis of science. That made it difficult for Dr. Hamburg to go against the conclusions of the F.D.A.’s own staff and the outside experts on its advisory committee.
There was also pressure to uphold the integrity of the accelerated program that was used to approve Avastin for breast cancer in 2008. That program allows the F.D.A. to provisionally approve drugs with less than the usual evidence of effectiveness, subject to further confirmation.
The agency has been criticized for failing to make sure the follow-up studies are done, or to remove approvals if those studies did not confirm the expected benefit. The case of Avastin, in which subsequent studies did not show the same level of effect as the initial study, is one of only a few in which an approval has been revoked and the first one in which the manufacturer had requested a hearing to appeal the proposed revocation. Daniel Carpenter, a professor of government at Harvard and author of the book “Reputation and Power: Organizational Image and Pharmaceutical Regulation at the F.D.A.,” said in an e-mail that the decision would make it easier for the agency to take more risks in granting accelerated approval because “with Avastin, the agency has sent a message that accelerated approval is neither absolute nor irreversible.” Even before the decision Friday, a handful of insurers had stopped paying for Avastin as a treatment for advanced breast cancer. Most insurers had said they would wait for the commissioner’s decision before evaluating their policies.
Medicare is obligated to pay for off-label use of cancer drugs that are listed in certain references, like the one published by the National Comprehensive Cancer Network, an organization of major cancer hospitals. In July a committee of breast cancer specialists from those centers reaffirmed that Avastin should remain listed as “an appropriate therapeutic option for metastatic breast cancer.” A third of the committee members had financial ties to Genentech, according to Dr. Hamburg’s memorandum.
It appears Avastin has lost its perch as the world’s best-selling cancer drug to Roche’s own Rituxan, a lymphoma medicine. Global sales of Avastin in the first nine months of 2011 declined 8 percent, to 3.94 billion Swiss francs, or about $4.3 billion, Roche reported. In the United States alone, sales fell more sharply, down 15 percent to 1.77 billion Swiss francs, or $1.93 billion.
An initial clinical trial that was the basis for the provisional approval showed that Avastin, combined with the drug paclitaxel, which is also known by the brand name Taxol, delayed the progression of disease by about five and a half months, compared to use of paclitaxel alone.
But in subsequent studies, in which Avastin was combined with different chemotherapy drugs, tumor growth was delayed by one to three months. Avastin did not prolong lives at all, nor did it improve quality of life.
Many breast cancer specialists say that Avastin does appear to work very well for some patients, and some advocates have said the drug should be left on the market for the sake of those patients. But Dr. Hamburg said there was no way to determine in advance who those patients were, so many women would use the drug. “The evidence does not justify broad exposure to the risks of this drug,” she wrote.
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