As pharma companies underwrite three-fourths of the U.S. Food and Drug Administration’s budget for scientific reviews, the agency is increasingly fast-tracking expensive drugs with significant side effects and unproven health benefits.
Nuplazid, a drug for hallucinations and delusions associated with Parkinson’s disease, failed two clinical trials. In a third trial, under a revised standard for measuring its effect, it showed minimal benefit. Overall, more patients died or had serious side effects on Nuplazid than after receiving no treatment.
Patients on Uloric, a gout drug, suffered more heart attacks, strokes and heart failure in two out of three trials than did their counterparts on standard or no medication.
Nevertheless, the FDA approved both of these drugs — with a deadly aftermath. Uloric’s manufacturer reported last November that patients on the drug were 34 percent more likely to die from heart disease than people taking an alternative gout medication. And since the FDA fast-tracked approval of Nuplazid and it went on the market in 2016 at a price of $24,000 a year, there have been 6,800 reports of adverse events for patients on the drug, including 887 deaths as of this past March 31.
The FDA is increasingly green-lighting expensive drugs despite dangerous or little-known side effects and inconclusive evidence that they curb or cure disease. Once widely assailed for moving slowly, today the FDA reviews and approves drugs faster than any other regulatory agency in the world. Between 2011 and 2015, the FDA reviewed new drug applications more than 60 days faster on average than did the European Medicines Agency.
Europe has also rejected drugs for which the FDA accelerated approval, such as Folotyn, which treats a rare form of blood cancer. European authorities cited “insufficient” evidence of health gains from Folotyn, which shrinks some tumors but hasn’t been shown to extend lives. It costs more than $92,000 for a seven-week course of treatment, according to research firm SSR Health.
As patients (or their insurers) shell out tens or hundreds of thousands of dollars for unproven drugs, manufacturers reap a windfall. For them, expedited approval can mean not only sped-up sales but also — if the drug is intended to treat a rare disease or serve a neglected population — FDA incentives worth hundreds of millions of dollars.
“Instead of a regulator and a regulated industry, we now have a partnership,” said Dr. Michael Carome, director of the health research group for the nonprofit advocacy organization Public Citizen, and a former U.S. Department of Health and Human Services official. “That relationship has tilted the agency away from a public health perspective to an industry friendly perspective.”
“That relationship has tilted the agency away from a public health perspective to an industry friendly perspective.”
While the FDA over the past three decades has implemented at least four major routes to faster approvals — the current commissioner, Dr. Scott Gottlieb, is easing even more drugs’ path to market. The FDA okayed 46 “novel” drugs — whose chemical structure hadn’t been previously approved — in 2017, the most in at least 15 years. At the same time, it’s rejecting fewer medications. In 2017, the FDA’s Center for Drug Evaluation and Research denied 19.7 percent of all applications for new drugs, biologics, and efficacy supplements, down from a 2010 peak of 59.2 percent, according to agency data.
President Trump has encouraged Gottlieb to give patients faster access to drugs. “You’re bringing that down, right?” Trump asked the commissioner at a May 30 event, referring to the time it takes to bring drugs to market. “You have a lot of good things in the wings that, frankly, if you moved them up, a lot of people would have a great shot.”
Faster reviews mean that the FDA often approves drugs despite limited information. It channels more and more experimental treatments, including Nuplazid, into expedited reviews that require only one clinical trial to show a benefit to patients, instead of the traditional two.
The FDA also increasingly allows drugmakers to claim success in trials based on proxy measurements — such as shrunken tumors — instead of clinical outcomes like survival rates or cures, which take more time to evaluate. In return for accelerated approval, drug companies commit to researching how well their drugs work after going on the market. But these post-marketing studies can take 10 years or longer to complete, leaving patients and doctors with lingering questions about safety and benefit.
“Once you have that paying relationship, it creates a dynamic that’s not a healthy one.”
“Clearly, accelerated approval has greater uncertainty,” Dr. Janet Woodcock, head of the FDA’s Center for Drug Evaluation and Research, said in an interview. When only a single trial is used for approval, “in some cases, there may be more uncertainty about safety findings or with the magnitude of effectiveness.”
She attributed the increased use of expedited pathways to more drugmakers developing treatments for rare diseases, “where there’s unmet need, and where the patient population and providers are eager to accept more uncertainty.”
The FDA’s growing emphasis on speed has come at the urging of both patient advocacy groups and industry, which began in 1992 to contribute to the salaries of the agency’s drug reviewers in exchange for time limits on reviews. In 2017, pharma paid 75 percent — or $905 million — of the agency’s scientific review budgets for branded and generic drugs, compared to 27 percent in 1993.
“The virginity was lost in ’92,” said Dr. Jerry Avorn, a professor at Harvard Medical School. “Once you have that paying relationship, it creates a dynamic that’s not a healthy one.”