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A college student with a rare disease was one of President Donald Trump’s special guests at his address to Congress Tuesday night, which happens to be Rare Disease Day.
Megan Crowley was diagnosed with Pompe, a rare and deadly genetic disorder, when she was 15 months old. Doctors gave her six months to live.
Instead of accepting Megan’s fate, her father, John, founded a company to search for a cure. The company, Novazyme Pharmaceuticals, eventually created an enzyme replacement therapy for Pompe, which Crowley’s son was also later born with. The Crowley children are still treated with the drug today, according to Stat News. (The family was also profiled in the book The Cure, which inspired the 2010 Harrison Ford movie Extraordinary Measures.)
Tonight, Trump used the Crowleys’ story to take take a shot at the Food and Drug Administration, which he’s been lambasting for its sluggishness over the past several months.
“Our slow and burdensome approval process at the Food and Drug Administration keeps too many advances, like the one that saved Megan's life, from reaching those in need,” he said. “If we slash the restraints, not just at the FDA but across our government, then we will be blessed with far more miracles just like Megan.”
Unfortunately, that’s not how it works. According to drug industry experts, and those who study the FDA, the agency isn’t what gets in the way of drug innovation. In fact, it’s already the fastest drug regulatory agency in the world.
It’s not the FDA that gets in the way of innovation — it’s the limits of our knowledge
Trump has vowed to cut 75 to 80 percent of government regulations. “Instead of it being 9,000 pages, it’ll be 100 pages,” Trump told a group of pharmaceutical company executives in January, presumably in reference to FDA’s guidance and rules.
One of the key notions that undergirds Trump’s view of the FDA is that if the agency just got rid of some of the pesky restrictions for drug approval, we could have a golden age in drug development, not just for rare diseases, but all diseases.
To test this idea, I asked a longtime pharmaceutical scientist (and conservative), Derek Lowe, for his views. In his 28 years in the lab, Lowe has seen hundreds of thousands of compounds tested on a huge variety of drug targets. But he has never brought a drug to market.
The reason? “We don’t know how to find drugs that work,” he said.
For every 5,000 compounds discovered at this "preclinical" phase of drug development, only about five are promising enough to be tried in humans. That’s a success rate of 0.1 percent.
True drug innovation comes from painstaking tinkering and a dash of luck. “We have 3 billion years of spaghetti-tangled gibberish to deal with. And unless you’ve done [drug development], it’s very hard to get across how hard it is,” Lowe said. “I don’t know of anything that’s harder.” Biochemistry and cell biology are “like alien nanotechnology,” he added.
So the real hurdle researchers face when it comes to finding new drugs for people isn’t overcoming a stringent regulator; it’s grappling with human biology in the lab.
The FDA is the fastest regulatory agency in the world
In the 1980s and ’90s, Congress and the FDA created several programs to speed up the development and approval process for new pharmaceuticals: the “orphan drug” designation (for diseases just like Megan’s), priority review, fast track, and accelerated approval.
These programs were intended to push the most clinically important, innovative drugs — medicines to treat rare, serious, or life-threatening diseases — out to patients more quickly, often on the basis of more limited and less rigorous clinical trial data.
“These pathways along with increased funding for FDA drug reviews from user fees enacted first in 1992 were successful,” said Aaron Kesselheim, an associate professor of medicine at Brigham and Women’s Hospital, in an email.
The average total review time fell from 30 months in the 1980s to about 8.5 months today. The FDA is now the fastest drug regulatory agency in the world, he added.
There's little evidence that speeding up approval times has helped spur innovation
The more important question is whether expedited FDA pathways increased the number of innovative new therapeutic options for patients — whether speeding up drug approvals has ushered in more medical “miracles” — and here the data is far less clear.
“Some transformative drugs, like imatinib (Gleevec) for chronic myeloid leukemia, have definitely benefited from speedier FDA pathways,” Kesselheim said. But research continues to show that the majority of drugs that have come onto the market offer little or no improvement over the status quo.
For example, several studies have found that since the mid-1990s, about 85 to 90 percent of new drugs that have come onto the market don't offer any clinical advantages for patients compared with existing therapies. In other words, the miracles remain elusive.
More worryingly, the special expedited development and approval pathways have become the rule, rather than the exception. Newer research, led by Kesselheim in the BMJ, looked at a database of all new medicines approved by the FDA between 1987 and 2013 and found that over the past two decades, the proportion of new drugs qualifying for at least one of the FDA's expedited programs has increased by 2.4 percent per year.
Kesselheim and his colleagues also concluded that "this trend is being driven by drugs that are not first in class and thus potentially less innovative." So there's little evidence that speeding up approval times has helped spur innovation.
Some even argue that if you want to bolster medical innovation, you need to look well beyond the FDA. Yale FDA researcherJoe Ross says some of the biggest barriers occur in the world of insurance payers. “Medicare essentially pays for almost everything [the] FDA approves. If payers were making more coverage decisions — including reimbursing more effective, safer medications — based on value, that would be a huge incentive to innovate better products,” he says.
Before dismantling the agency, Trump will also need a firmer grasp of the history of medical regulation and why it’s there in the first place. As Peter Thiel, the Silicon Valley billionaire who is helping to guide Trump’s search for a new FDA head, has said, "You would not be able to invent the polio vaccine today.”
Yale medical historian Jason Schwartz disagreed: “This assertion is at best ahistorical, if not altogether meaningless.”
The famous Salk polio vaccine trial in 1954 involved more than half a million children, “a number that would be unacceptable today,” Schwartz explained. And shortly after the vaccine’s introduction, problems with its production resulted in the Cutter Incident: Vaccines with live polio virus (instead of killed virus) were administered to thousands of American children, sickening 40,000, leaving 200 paralyzed, and killing 10.
Over the past half-century, we’ve seen a number of new vaccines come onto the market, including shots to prevent hepatitis B and meningococcal, which were developed without harming children. “It's exactly the production safeguards and ongoing oversight of vaccines and other products by the FDA today — both before and after approval — that keep these kinds of preventable tragedies from happening again,” Schwartz said. Hopefully Trump keeps that in mind as he guides the agency to “slash” restraints.
