Accelerated FDA approval and pricey drugs make a rotten combo, doctors argue

The FDA should do more to hold down prices of drugs given accelerated approval, a new NEJM editorial argues.

Should drugs that win FDA approval on an accelerated path—often without strong evidence of efficacy—command the same high prices as products that undergo the full menu of agency scrutiny?

Not necessarily, two doctors contend in a new journal article. And they have some ideas for bringing the costs of those drugs way down, at least until their makers can prove they really work.

The ideas—which include lower prices until drugs prove themselves out in confirmatory trials—come amid an unprecedented debate over the price tags on drugs in the U.S. Over the past 18 months and more, controversy after controversy have prompted politicians and the public to call for some sort of action to hold down drug costs.

Accelerated approval is a problem because it forces Medicare and Medicaid to pay for drugs that can cost hundreds of thousands of dollars and yet may not work for many patients, argue Walid Gellad, associate professor of medicine at the University of Pittsburgh, and Aaron Kesselheim, associate professor of medicine at Brigham & Women’s, in an editorial in the New England Journal of Medicine.

At the same time, private insurers may decline to cover those drugs, denying patients access to products that were supposed to get to them faster.

Accelerated approval was invented in the 1990s to speed HIV drugs to market, and those products did ultimately prove effective, Gellad said in an audio interview posted with the NEJM article. “It came out of the notion that if we wanted to get drugs to patients faster, then we couldn’t necessarily wait sometimes to get the final confirmation on their benefit,” Gellad said.

Accelerated approval has since been applied to many therapeutic classes, most notably cancer, where results have been “a little more of a mixed bag,” Gellad said. He pointed to a study of 15 cancer drugs approved under an accelerated path over a four-year period ending in 2012, six of which later proved to offer no survival benefit.

In the NEJM paper, the authors cite many recent examples of pricey drugs with questionable efficacy. They include Roche’s Avastin, which was approved to treat breast cancer based on a surrogate survival measure that was later disproved, causing the FDA to remove the indication from the label.

Then there's Sarepta’s Exondys 51, which won accelerated approval to treat Duchenne muscular dystrophy last September based on a tiny trial that the FDA itself acknowledged did not establish a clear clinical benefit.

The FDA requires drugmakers who gain accelerated approval to perform post-marketing studies to prove efficacy—and therein lies an opportunity for the healthcare system to save money, Gellad and Kesselheim propose. They suggest drug manufacturers be required to discount products until confirmatory trials are complete, or that a portion of the full price they’re charging be held in escrow until the results of the trials are available.

“We see the value in getting products that qualify for accelerated approval to market for patients, but we believe the price paid by taxpayers should reflect the strength of the available evidence about the drug’s clinical impact,” the authors write.

Of course, drugmakers could make up for those discounts by simply hiking list prices, so the authors offer an alternative idea: Government payers would reimburse manufacturers for the cost of making the drug, plus an agreed-upon markup, until the confirmatory trials are finished.

Gellad and Kesselheim also propose that the FDA require confirmatory trials to be completed in a timely fashion. And they suggest drugs that cost more than $100,000 per year be subject to an economic analysis performed by the Centers for Medicare and Medicaid Services or the Government Accountability Office. The idea would be to prove that the high cost of the drug isn’t causing “financial turmoil” in government-run insurance programs, they write.

The NEJM paper lists several other pricey drugs approved under the accelerated path since 2011. They include Amgen’s leukemia drug Blincyto ($56,262 per month), Novartis’s lung cancer treatment Zykadia ($14,628) and Merck’s cancer blockbuster Keytruda ($9,252).

Gellad acknowledges there’s no precedent for the steps he and Kesselheim suggest, but he predicts more controversies like the one that swirled around Sarepta after Exondys was approved.

“FDA does not take cost into account when it determines whether or not it’s going to approve a drug, and generally Medicare typically will also a cover a drug,” said Gellad in the NEJM interview.

“The point we make," he added, "is should we be paying the same amount for a drug for which there is no clear evidence of clinical benefit, or should we wait until there is that final evidence of clinical benefit before we pay that full amount? That’s why we discuss issues around whether there are different ways to pay,” he said.