In a series of 6-0 votes, an advisory committee to the Food and Drug Administration endorsed the agency’s proposal to revoke the approval of the drug for use against advanced breast cancer.
The committee members voted that the drug was neither safe nor effective. It also unanimously rejected a proposed compromise offered by the drug’s manufacturer, Genentech, that the approval remain in place while the company conducts another clinical trial to try to confirm that the drug works.
The votes came at the end of an emotional two-day hearing at which about a dozen women, many of whom said the drug was saving their lives, and some cancer support group advocates, pleaded with the F.D.A. and the advisory committee to keep the drug available.
“A panel of six, none of which specialize in metastatic breast cancer, decided that we are statistically insignificant,” Crystal Hanna, one of the patients who testified, said in an e-mail after the vote. “How do I explain that to my 4-year-old and 7-year-old?”
But the members of the advisory committee said the results from clinical trials suggested Avastin was not helping women, though it was exposing them to potentially serious side effects like high blood pressure, gastrointestinal perforations and hemorrhaging.
“The agency has to look at protecting a larger number of patients,” said one committee member, Dr. Ralph Freedman, a gynecologic oncologist at the M. D. Anderson Cancer Center in Houston. “Sometimes they have to make a decision that doesn’t favor individual patients, but it’s on the basis of the whole.”
Avastin received so-called accelerated approval for metastatic breast cancer in 2008 under a program that allows drugs for serious diseases to reach the market quickly, subject to further study.
The F.D.A. said in December that these later studies had not confirmed the initial findings that Avastin was effective, so the agency proposed to revoke the approval. The hearing this week, which took place on the F.D.A. campus in Silver Spring, Md., was to hear Genentech’s appeal.
The final decision will be made by the commissioner of the F.D.A., Dr. Margaret A. Hamburg. She is not obligated to follow the advice of the committee.
Genentech, a subsidiary of Roche, and some patient groups are trying to bring Congressional pressure to bear on the F.D.A. At a time of controversy over the federal health care legislation, the Obama administration might not want to provoke renewed accusations of rationing care, which had been leveled during earlier stages of the agency’s deliberations over revocation.
Edward Lang Jr., a spokesman for Genentech, said the company would propose some middle grounds to the F.D.A., like restricting use of the drug to aggressive cancers or changing the drug’s label.
Genentech might also challenge an unfavorable decision in court.
Even if the breast cancer approval is withdrawn, Avastin will remain on the market as a treatment for several other types of cancer, so doctors could use it off label to treat breast cancer. But insurers might be less likely to pay, which would put Avastin, which costs about $88,000 a year, out of reach for most patients.
Even that is not certain. Medicare is supposed to pay for off-label uses of cancer drugs listed in references called compendia. One such compendium, published by the National Comprehensive Cancer Network, reaffirmed support for Avastin last year.
Still an explicit rejection of the drug by the F.D.A. might prompt the compendia to re-evaluate the drug or prompt insurers to ignore the compendia.
“My own guess is that third-party payers, including Medicare and Medicaid, would look at the F.D.A. decision and say this is a special circumstance,” said Dr. Harold J. Burstein of the Dana-Farber Cancer Institute in Boston. Dr. Burstein, who is on the cancer network’s breast cancer guidelines committee, said he did not know if the committee would re-examine Avastin at its annual meeting next month.
Avastin is the world’s best-selling cancer drug, with sales last year of roughly $7 billion. Analysts have estimated that loss of the breast cancer indication could cost Roche as much as $1 billion a year.
Sales of Avastin have already started dropping as doctors use it less. Mr. Lang, the Genentech spokesman, said that only 20 percent to 25 percent of eligible breast cancer patients in the United States were now receiving the drug, down from 60 percent a year ago. There are about 29,000 new cases a year of the type of breast cancer for which Avastin is approved, he said.
The committee’s votes on Wednesday were not surprising given that five of the six members voted the same way last July, when the committee initially recommended the approval be revoked.
The trial that led to approval indicated that Avastin, when combined with the chemotherapy drug paclitaxel, delayed the median time before tumors got worse by 5.5 months compared with paclitaxel alone.
But in two subsequent studies, Avastin delayed tumor progression by only 1 to 3 months. And none of the studies, including the original one, showed Avastin prolonged women’s lives or improved the quality of their lives.
“We’ve tried to slice this pie in a lot of different ways to try to find some kind of benefit for this drug,” said one committee member, Dr. Mikkael Sekeres of the Cleveland Clinic. “All we’re left with are crumbs.”
Genentech argued that subsequent trials might not have shown as large a benefit because Avastin had been combined with different chemotherapy drugs. It said the approval should remain in place while it conducted another study in which Avastin would be combined with paclitaxel, as in the original study.
“The law provides this flexibility and this middle course best meets the purposes of accelerated approval to facilitate needed treatment options,” Michael S. Labson, a lawyer representing Genentech, told the committee.
But the trial would take several years. Committee members suggested that the F.D.A. had to act to maintain the integrity of the accelerated approval program.
“We have a standard,” said Dr. Wyndham Wilson of the National Cancer Institute, a committee member, “and we shouldn’t be changing that standard unless we have a very good reason.”
Article source: http://feeds.nytimes.com/click.phdo?i=9eabeab3c503071694b8c6a76de2c0ec
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