Trenton, N.J. Under growing scrutiny since the blockbuster painkiller Vioxx was pulled from the market, the Food and Drug Administration in recent months has rejected a slew of experimental drugs or delayed their approval and required more data.
Besides keeping drugs some patients might desperately need off the market, the rejections have battered drug company stock prices and are expected to increase the cost and time it takes to develop a new drug, not to mention the price of developing future ones.
Denials and delays have hit everyone from pharmaceutical giants such as GlaxoSmithKline PLC, Merck & Co., Novartis AG, Sanofi-Aventis and Wyeth down to struggling startups trying to get their first drug on the market. The FDA also has recently stiffened warnings on several drugs, most prominently diabetes drugs Avandia and Actos, and five months ago made Novartis withdraw its constipation drug, Zelnorm.
"There have been no systematic changes in how we are approaching the approval standards for new applications," FDA spokesman Christopher Kelly said in an e-mail. "Whether the current public debate and criticism of FDA on drug safety has played any role in our actions is very hard to quantify."
But Chris Milne, associate director of the Tufts Center for the Study of Drug Development, said Friday the FDA has systematically implemented more controls for scrutinizing drugs, particularly for heart and liver side effects. While he thinks the trend on approvals is not yet clear, he said the FDA now is requiring experimental drugs similar to ones already on sale to be more effective and safer than their predecessors.
Some experts say they already see a trend toward increased rejections, although drugs for life-threatening diseases or conditions with no good current treatment are generally being approved.
"The FDA is being more cautious," analyst Steve Brozak of WBB Securities said, explaining that FDA staff now realize new drugs will be used by many patients beyond those intended - known as off-label use because the drug is taken for another condition than the one it was approved to treat. That often boosts the chances that some patients will be harmed by side effects.
He sees the FDA mentality now as: "It's got to be so safe that we're not going to be criticized ever" for approving a drug.
The agency has approved 61 percent of drug applications through mid-August, down from 73 percent in the same period last year, according to BioMedTracker, a biotech and pharmaceutical research service.
James Kumpel at Friedman, Billings, Ramsey & Co. just published a report showing FDA approvals of "new molecular entities" - drugs made from new chemical compounds rather than just twists on existing drugs - so far this year are at their lowest level in at least a decade. Only seven were approved through the end of July, versus an average of 12 over the first seven months of each year since 1998.
"The FDA certainly has made it more difficult for pharmaceutical companies by pushing for more data and for more participants and for longer studies," said Kumpel, barriers he said will start limiting the number of new blockbusters.
Already, the average cost of shepherding a potential drug from discovery through approval is $980 million, up from $802 million in 2000, and the process takes 14.2 years on average, according to Tufts.