Advisers Tell FDA to Curb EPO Use

An outside advisory panel has asked the Food and Drug Administration to issue new warnings that will dramatically scale back the use of anti-anemia drugs if the warnings are heeded by the nation's oncologists.

You've seen those television ads. They show beaming older cancer patients playing with their grandkids. Why? Now they have the energy because of J&J's Procrit and Amgen's Aranesp.

These are the same drugs that were the subject of a front page story in the New York Times yesterday that documented the lucrative rebates that physicians rake in from those companies for prescribing (and over-prescribing) the drugs. Most of the overprescribing is done in the name of reducing the fatigue that accompanies chemo.

The FDA reviewer who presented the agency's analysis to the Oncology Drugs Advisory Committee had a big problem with those claims. "Improved quality of life, fatigue and other symptoms associated with anemia has not been established in properly conducted, randomized, double-blind, placebo-controlled trials," he said.

What has been been in shown in a handful of recent trials is that raising red blood cell counts to near normal levels in chemotherapy patients actually leads to worse outcomes. FDA reviewer Vinni Juneja pointed to two head-and-neck cancer trials that had to be terminated early because they increased mortality. Another trial involving breast cancer patients increased mortality and shortened the time to tumor progression -- a key indicator that the cancer is spreading.

"How is it possible that something that was supposed to help me might have made things worse?" asked Lilla Romeo, a 60-year-old breast cancer patient who's been battling the disease since 2000. The false hope offered by the ads run by the companies was "both insulting and cruel," she said.

Once again, a drug company's efforts to expand the use of a blockbuster drug has boomeranged. Vioxx' cardiovascular risks were only conclusively proven when Merck paid for a massive trial that sought to show that the painkiller curbed colon polyps, which may be precancerous. In this case, Amgen wanted to show that taking high doses of EPO improved cancer outcomes. Several studies had suggested a "potential therapeutic benefit," Roger Perlmutter, Amgen's chief scientist, told the committee.

Stock analysts will spend years pondering why Amgen wanted to get an anti-cancer indication for Aranesp in the first place. Their lucrative rebates, coupled with numerous studies (never placebo-controlled) showing improved "quality of life" for patients, had turned the oncology profession into a willing accomplice to their marketing schemes.

"The problem is that the doctors get about $1,200 for every dose of the drug that they give," said Otis Brawley, a professor of oncology at the Wiship Cancer Institute in Bethesda, Md. and a member of the advisory committee. "They don't have to sign any conflict of interest statements like we do. That's a real problem." Given the high profile nature of the controversy, the FDA finally managed to put together an advisory committee without any conflicts of interest.

And at the end of the day, a committee without any ties to Amgen or J&J asked the FDA to specifically state in the label that EPO shouldn't be used in cancer patients where trials have shown adverse safety signals for that particular type of cancer -- like breast and head-and-neck cancers. They also voted to lower the red blood cell count at which anti-anemia treatment should be initiated.

And, they asked the FDA to demand more clinical trials from Amgen and J&J to definitively test the proposition that anti-anemia treatment actually makes people feel better (there's no doubt that it reduces the need for blood transfusions, its original approved indication, but that can be achieved at greatly reduced use of the drugs).

Curiously, the only time that Richard Pazdur, who heads the FDA's cancer drugs division, spoke at length during the meeting was to criticize his own agency on its monitoring of direct-to-consumer advertising. Just like in the Vioxx case, the ads played a major role in triggering this latest drug safety crisis. "We have a lot of problems with advertising, but the office (in charge of monitoring ads) has a lot of discretion," he said. "The FDA's chief counsel office obviously sets the tone.

"I want to thank the advisory committee for bringing this up," he continued. "They (the FDA) have to give the American people a good explanation for why these ads were allowed to continue."

Pazdur's comments provided a proper epitaph for yesterday's action in the Senate, which overwhelming passed reauthorization of FDA user fees. Admittedly, the bill included a few measures that give the agency more oversight powers. But one of the amendments tacked on at the last minute to placate the broadcast and publishing industries watered down the agency's ability to force ads off the air.

And another amendment, which would have severely limited the FDA's ability to appoint outside advisers with conflicts of interest, was narrowly defeated. Today's vote showed what happens when the FDA appoints committees without such conflicts. They do the right thing.

Posted by gooznews at May 10, 2007 06:28 PM