What Is Up With the FDA? What Comes Next?

^{Image courtesy National Human Genome Research Institute}

The U.S. Food and Drug Administration (FDA) is supposed to encourage effective medical advances while also ensuring that patients and research subjects are protected. This dual mandate demands tricky judgment calls that are made more difficult by outside pressures of several kinds, political, judicial, and especially commercial. This April story at Bloomberg examines one deeply troubling pattern of regulatory capture:

Americans Are Paying Billions to Take Drugs That Don’t Work
Companies are increasingly using fast-track approval processes to get unproven treatments to patients.

Bloomberg has been scrutinizing the process of developing and authorizing effective treatments for decades. As long ago as 2005, they published a major Special Report called Big Pharma’s Shameful Secret, which blew the whistle on “this industry’s widespread corrupt practices … [and] FDA’s abdication of its public responsibility.” We discussed this still-relevant report seven years ago in this post:

Blinded by Bad Science and Bad Oversight

On July 8 of this year, Tom Nicholson of Advance Access & Delivery, a non-profit global health organization, and Jay Bhattacharya, professor of health policy at Stanford Medical School, explained a new twist on evading appropriate oversight. They wrote in Newsweek:

The FDA Just Quietly Gutted Protections for Human Subjects in Research
… At its core, the new FDA rule change allows any IRB [institutional review board] … to grant exemptions to informed consent requirements based on “minimal risk.” Based on vague guidelines, it effectively gives thousands of IRB committees the unilateral ability to determine that researchers need not obtain true informed consent from research participants.

This seems unfortunately consistent with recent practice at the FDA. In June 2023, the agency gave limited approval to a gene therapy for Duchenne muscular dystrophy called Elevidys, from Sarepta Therapeutics, although STAT+ reported that FDA reviewers were “leaning toward rejecting.” As reported in Time, some officials were not entirely convinced that the effects seen in lab tests (increased dystrophin levels) would translate to real-world benefits. The FDA decided that only patients aged four or five, the age group that seemed to have benefited most in early clinical trials, were eligible for the one-time treatment priced at $3.2 million. The company estimated (p. 13 of this “forward-looking statement”) that “ELEVIDYS has the potential to be cost-effective in a range of $5 million to $13 million compared to standard-of-care alone” – so the price set was a bargain.

One year later, on June 20, 2024, Sarepta announced that FDA had expanded approval to cover most Duchenne patients of all ages. On June 21, the company’s stock rose about 40%, to 160.72, adding almost $4 billion to its market value. Four weeks later it is still at 146.90, higher than it has been since 2020.

This decision was not made according to typical FDA processes: it was driven by Peter Marks, head of the Center for Biologics Evaluation and Research (CBER) at the FDA, who has been pushing for “accelerated approval” in particular for gene therapies aimed at rare diseases. Doctors for America strongly condemned the FDA’s approval of Elevidys, and were “deeply alarmed that this approval appears to have been entirely the decision of one individual.” STAT reporters Jason Mast and Matthew Herper reported that Marks

overruled three review teams and two top lieutenants, who wrote that the data Sarepta submitted “cast significant uncertainty regarding the benefits of treatment.” [emphasis added]

To be fair, approval decisions are often difficult balancing acts, as Marks has explained:

“We always are going to keep safety, front and foremost. But I think the issue here is we can’t be so careful about our approvals under accelerated approval that we prevent potentially lifesaving therapies from getting to market in a timely manner.”

A follow-up story by Herper on July 2 added more detail about “the unilateral decision by Peter Marks” and also reported that he had emailed the FDA for clarification but their reply “did not answer a single question that was asked in the original email.”

Meanwhile, a new era of political and judicial pressure on the FDA seems close at hand. Stem cell biologist Paul Knoepfler, whose blog The Niche is a must-read in the field, noted that Utah passed a law in March legalizing “placental stem cell therapies” that the FDA has not approved, and Nevada passed one last year that also seems to be inconsistent with federal regulations. This of course may set up a legal conflict between the federal and state authorities. 

As Knoepfler reminds us, the Supreme Court recently overturned the Chevron decision, which had held that a court was required to uphold a federal agency’s interpretation of a law as long as it was reasonable. In other words, a court could now simply override a civil service decision. Justices Kagan, Sotomayor, and Brown dissented, calling this ruling a “jolt to the legal system” and a “judicial power grab.” 

This ruling, coupled with several other recent cases, writes Robert Klee of the Yale School of the Environment, “may have cracked the foundations of federal environmental and public health protections beyond repair.” 

All this means that the future of the FDA is completely unclear. Drug companies have devised creative ways to shape the decisions of the agency tasked with regulating them. Senior officials within the agency can and do overrule the experts they themselves have appointed. Now the agency’s authority has been undercut by the Supreme Court. How will the FDA – and we – react if some judge with strong opinions and little or no scientific knowledge overrules its decisions?