Healthy Skepticism Library item: 19074

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Publication type: news

Mundy A
FDA Says Drug Firms Didn't Finish Follow-Ups
The Wall Street Journal 2011 Feb 9
http://online.wsj.com/article/SB10001424052748703313304576132560915752074.html

Full text:

Federal officials Tuesday questioned companies that make six cancer drugs about their failure to complete follow-up studies they promised to conduct in exchange for accelerated approval.

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At a public meeting, Food and Drug Administration officials and its committee of outside cancer experts discussed the importance of follow-up, while the companies cited challenges including the difficulty of enrolling patients in trials for already-approved drugs.

The issue is one of the most sensitive for the FDA, which says it wants to speed potentially lifesaving drugs onto the market while also making sure there’s evidence the drugs work. The agency faces pressure from patients and doctors who say it’s better to provide fast access than to wait for full data.

In a compromise dating from the early 1990s, the FDA has granted accelerated approval several dozen times to cancer drugs based on preliminary evidence. Companies then promise to confirm the evidence in follow-up studies.

The FDA can fine companies millions of dollars or revoke approval if the evidence isn’t forthcoming. At Tuesday’s meeting, FDA officials stopped short of making those threats against the companies making the six drugs—which include Amgen Inc., GlaxoSmithKline PLC and Eli Lilly & Co.—but spoke generally about the value of timely confirmation.

“These confirmatory trials are as important—if not more important—than the initial trials leading to the accelerated approval,” said Richard Pazdur, the head of the FDA’s cancer division. He said some companies have taken more than six years to complete the trials.

The meeting took place in the shadow of a recent announcement by the FDA that it intends to revoke the accelerated approval of the blockbuster drug Avastin for use in treating breast cancer, a move that has jolted the industry and provoked outrage among many women across the country who have asked Congress to intervene.

The FDA said follow-up studies by Avastin maker Genentech, a unit of Roche Holding AG, failed to show that the drug significantly delays the spread of tumors in breast-cancer patients. Genentech is appealing the decision and says the FDA misinterpreted the studies.

Former FDA Deputy Commissioner Scott Gottlieb, who now invests in and consults for drug companies, was critical of some of the FDA mandates and said the result might be to delay badly needed drugs.

“The oncology division has long felt that the accelerated approval provisions were too permissive and have worked over a period of about eight years to unwind the spirit of the statute,” he said.

Others said the bar for accelerated approval was too low. “We are willing to accept drugs with the most minimal evidence,” said Silvana Martino, who runs the breast-cancer program at the Angeles Clinic and Research Institute in Santa Monica, Calif.

It was the first such meeting at the FDA since 2005. Dr. Pazdur said the agency wants to hold the gathering every year because there’s “nothing like the light of day” to show where companies need to perform. He also said that if companies aren’t confident they can complete follow-up studies on time, they may want to avoid seeking accelerated approval in the first place.

Several companies said Tuesday that they had difficulties finishing some of the mandated studies because they could not find enough patients to generate reliable results.

One drug, Glaxo’s Bexxar, was initially approved in 2003 for a specific lymphoma. It got accelerated approval in 2004 for use in patients with a rarer form of the cancer who, in most cases, had exhausted other treatment options, said a Glaxo spokesman. With smaller patient pools, it can be hard to recruit the numbers needed to conduct the trials, he said.

Lilly said it has met with the FDA to discuss data for the drug Erbitux in some types of colorectal cancer. The company said it continues to “work diligently to fulfill the remaining postmarketing commitment for Erbitux, which we expect to do later this year.” Amgen said it met its commitments with due diligence.

The FDA has agreed that some trials promised by companies can’t be carried out because the treatment protocols they were designed to test became outdated.

European regulators have a program similar to accelerated approval except that the conditional approval is granted only for a year, after which it can be renewed. That means companies have to show consistently that they are making progress toward meeting their commitment.

In five cases, studies failed to confirm benefit and drugs were withdrawn or faced new restrictions, according to the FDA. That happened in 2005 to AstraZeneca PLC’s lung-cancer drug Iressa, which failed to show survival benefit in a large trial and was pulled except for patients already on the drug.

“We expect a small percentage of products to fail to confirm a benefit. This is the trade-off for earlier availability of promising agents for severe and life-threatening diseases,” said Dr. Pazdur.