Drugmakers such as Pfizer Inc. (PFE) that win early U.S. approval of promising cancer treatments may face fines up to $10 million if they take too long to confirm effectiveness in follow-up studies, Food and Drug Administration officials said.
The FDA may also start requiring that such trials be under way before a drug can win expedited approval, John Johnson, a clinical team leader at the agency’s Division of Drug Oncology Products, and colleagues said in a report published online today in the Journal of the National Cancer Institute.
The agency’s accelerated-approval program came under scrutiny last year as New York-based Pfizer, the world’s biggest drugmaker, withdrew its leukemia drug Mylotarg after 10 years on the U.S. market and the FDA moved to revoke its 2008 clearance of Basel, Switzerland-based Roche Holding AG (ROG)’s Avastin for breast cancer. A drug can be pulled if subsequent studies don’t show it prolongs survival or improves quality of life.
“Indications that have received accelerated approval should not be on the market for unacceptably prolonged intervals in the absence of completed confirmatory trials,” Johnson and his colleagues wrote.
Follow-up studies had yet to be completed as of last July for 14 accelerated approvals granted in the past 12 years, according to the report. Among them was the 1999 clearance of Pfizer’s arthritis drug Celebrex to treat a rare colon condition and a 2005 approval of London-based GlaxoSmithKline Plc’s Arranon for lymphoma, the authors said. Pfizer acquired Celebrex as part of its 2003 purchase of Pharmacia Corp.
Faster Studies Sought
The agency could confirm efficacy faster by requiring that such trials be in progress before granting an accelerated approval, the report said.
“Such a requirement would ensure that accelerated approval is part of the development plan of a drug for a new indication and not an afterthought,” the authors wrote.
A 2007 law authorized the FDA to fine drugmakers as much as $10 million for “lack of due diligence” in conducting trials to confirm the benefits of drugs that win accelerated approval, according to the report.
“The FDA believes that this will be an effective new tool for dealing with lack of due diligence,” Johnson and his colleagues wrote.
The agency granted accelerated approval to 47 new uses for 35 drugs between December 1992 and July 2010, according to the report. Three of those treatments, including Mylotarg, were withdrawn after studies failed to confirm they worked.
The FDA in December proposed rescinding its approval for Roche’s top-selling drug Avastin for breast cancer after follow- up studies found the drug increased side effects without prolonging survival. Roche plans to tell the agency at a June hearing that breast cancer should remain an approved use for the drug in combination with chemotherapy, the company’s Genentech unit said last month.
Twenty-six of the FDA’s 47 early approvals were later converted to regular FDA clearance after studies confirmed clinical benefits, according to the report. The average time between accelerated approval and regular approval for those treatments was 4.7 years.
“The accelerated approval process has been successful in making promising new drugs available to cancer patients sooner than they would have been if they had undergone regular approval,” Johnson and his colleagues wrote.
The amount of time saved through the accelerated-approval process isn’t clear from the FDA officials’ report, Susan Ellenberg, a professor of biostatistics at the University of Pennsylvania School of Medicine, in Philadelphia, said in an accompanying editorial.
The regular drug-approval process could take less time than the separate sets of initial studies and follow-ups required for an accelerated approval, she said.
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