WASHINGTON – From 2003 to 2010, the U.S. Food and Drug Administration approved novel oncology drugs at a faster pace than did its European counterpart, according to a study published online on June 16.
Researchers at the nonprofit Friends of Cancer Research compared the performance of the two agencies, in part because the perception among investors, patients, and investigators has been that the American regulatory agency lags behind other nations when it comes to getting medications to patients.
But the findings – published on the website of the journal Health Affairs – came to an opposite conclusion, which was a surprise, said Ellen V. Sigal, chairperson and founder of FOCR and an author of the paper, at a briefing on Capitol Hill (doi: 10.1377/hlthaff.2011.0231).
The authors compared review times for new molecular entities in oncology for the study years of 2003-2010. Thirty-five were approved either by the FDA or the European Medicines Agency (EMA) during that time. The FDA approved 32 of the medications, with a median time of 182 days from time of submission of the application and approval.
The EMA approved 26 of the 35 drugs, with a median time of 350 days from submission to approval. Three of the drugs were approved by the EMA but not by the FDA: Ceplene (histamine dihydrochloride), Mepact (mifamurtide) and Yondelis (trabectedin). All three were considered by FDA advisory committees and deemed too risky for the benefits they offered.
Twenty-three drugs were approved by both agencies but were available in the United States first. The study focused on new drugs only and did not take into account supplemental approvals, which are common in oncology. But the initial approvals are more important because the therapies are often used off label, noted the authors. And many of the drugs were approved using the FDA’s special accelerated approval process, which mandates a faster review.
Much of the improvement in review times over the years is credited to the Prescription Drug User Fee Act (PDUFA) of 1992. Dr. Janet Woodcock, director of the Center for Drug Evaluation and Research, said at the briefing that before, "there was the perception that U.S. patients were disadvantaged to patients in other countries." While that may have been true in the 1980s and before PDUFA was enacted, FDA’s own analysis shows that every year, there’s been an increase in the proportion of new drugs that are first launched in America. Now, 60% of all pharmaceuticals are available in the U.S. first, said Dr. Woodcock.
The authors of the study backed that analysis, concluding that, "Contrary to repeated public assertions, we found that new oncology medicines are consistently available in the United States before they are in Europe, and they are more likely to be approved by the FDA than by the EMA."
Ms. Sigal said that the findings are encouraging, "but that doesn’t mean [the FDA] gets a free pass."
Dr. John Marshall, clinical director of oncology at the Georgetown Lombardi Comprehensive Cancer Center in Washington, agreed at the briefing that there is good news in the report, but that it should not be viewed as the big picture. Given the long road of drug discovery, drawing a conclusion from the approval times is like taking a snapshot of the final lap of the Indianapolis 500. "You can’t say this is what the whole race is about," said Dr. Marshall.
He noted the difficulty of drug discovery, long approval times for trials from institutional review boards, and drawn-out discussions between drug companies and the FDA that have no deadlines. And, he added, "Probably the biggest thing that holds up drug approvals, particularly in the United States, less so in other parts of the world, is patient participation" in clinical trials. With as few as 3% of Americans taking part in trials, it takes longer to determine whether a therapy is viable, said Dr. Marshall.
Drug approval times are a "lagging indicator" of the health of the oncology drug development process, said Jonathan Leff, a managing director at Warburg Pincus, at the briefing. The leading indicators – such as capital investment in life sciences and the number of applications for FDA approval – are very negative, he said.
Mr. Leff said the perception persists among investors and company executives that the FDA is a roadblock to drug development. He said there needs to be some improvement in the process at the agency, but added that, "I actually think the FDA leads the world in the application of science in a way that keeps up with the cutting edge."