Are FDA EUAs Now ‘Wishful Thinking’?

Several former FDA executives are voicing concerns about the wisdom of the agency issuing an emergency use authorization (EUA) for the malaria drugs chloroquine phosphate and hydroxychloroquine sulfate to treat Covid-19. In a lengthy ScienceInsider post, former FDA commissioner Magaret Hamburg said she fears the agency has taken “a step away from scientific rigor, to a system that is much more subject to all kinds of interference, from wishful thinking to frank political and economic motivations.”

Hamburg said she was “surprised and perturbed” by the EUA. “I understand the desire to find hope,” she said, “but we need more evidence than is currently available before we encourage widespread use.” She noted that valuable clinical trial evidence on the two drugs could have been gathered in a few weeks, but the EUA could make that more difficult. “Making the drugs available in a more widespread way might actually interfere with the ability to get the data we need,” she declared.

Former FDA commissioner Scott Gottlieb, who has emerged as an unofficial advisor to the White House on Covid-19, said the beneficial effects of the malaria drugs are likely to be so subtle that they will only be seen in large clinical trials.

Former FDA acting chief scientist Luciana Borio, who directed medical and biodefense preparedness for the National Security Council under President Trump, said, “You want the EUA to be seen by the public as a step the government is taking to facilitate access to a product that they truly believe has benefits that outweigh the risks, not ‘We’re not sure.’”

The article says current FDA commissioner Stephen Hahn first tried to temper Trump’s enthusiasm for the drugs, calling for clinical trials as a first step during a 3/19 news conference. Nine days later, with the trials ramping up, it says, the EUA authorized healthcare centers to draw on the strategic national stockpile’s massive supply of the drugs for “treatment of Covid-19 when clinical trials are not available, or participation is not feasible.” The agency said that in the absence of approved or available alternatives for treating Covid-19, the drugs’ known and potential benefits outweigh the known and potential risks.

Borio said in approving the EUA the agency overlooked the drugs’ record of failure against other viruses.

University of Minnesota infectious disease researcher David Boulware told ScienceInsider the EUA could slow testing of Gilead Science’s remdesivir because hospitalized patients will ask for the malaria drugs rather than participate in a clinical trial for the Gilead candidate.

Boulware and others said that while it may not have been the intention, the EUA might have made hydroxychloroquine the de facto standard of care for Covid-19, which could undermine the clinical trials of it and chloroquine.

Former FDAer Peter Lurie, who now heads the Center for Science in the Public Interest, said, “Why take a 50% chance of getting a placebo when you can be guaranteed to get a drug you’re hoping to get? Then you’re left in a situation where a drug is widely used and evidence of its effectiveness for this indication is never generated.”

Former FDA associate chief counsel Patricia Zettler, now an Ohio State University law professor, said “The idea that we have nothing to lose by trying anything with the smallest glimmer of hope is terribly misguided. As a society, we risk losing the opportunity to understand what actually works, and what doesn’t.”

ScienceInsider says FDA watchers are wondering how the agency will respond to the next remedy supported by anecdotal reports when facing public fears about a growing death toll and presidential pressure. “There is no shortage of candidates, including zinc, remdesivir, the Japanese flu drug favipiravir, and a stem cell product touted by Trump attorney Rudy Giuliani,” it says. It notes that the agency would not comment on such prospects but has already approved testing the stem cell product in a clinical trial of Covid-19 patients.

“When the evidence base for granting the EUA is as flimsy as this is, the question becomes ‘Whose EUA will not be granted, especially in the context of an epidemic?’” Lurie said. “What happens when the epidemic is not historically bad, when it’s just a bad season of the flu?”