FDA grants emergency authorization to COVID-19 convalescent plasma
Late last week, the New York Times reported that a planned emergency use authorization (EUA) for plasma taken from COVID-19 survivors had been put on hold after federal health officials including Francis Collins and Anthony Fauci raised concerns about the strength of the evidence.
Days later, neither Trump nor the heads of the US Food and Drug Administration (FDA) and the US Department of Health and Human Services (HHS) expressed such doubts at a press conference to discuss the EUA for COVID-19 convalescent plasma. Rather, the three men presented plasma as a big breakthrough.
“We saw about a 35% better survival in the patients who benefited most from the treatment. I just want to emphasize this point because I don’t want you to gloss over this — this number. We dream, in drug development, of something like a 35% mortality reduction,” said HHS Secretary Alex Azar.
Stephen Hahn, commissioner of the FDA, made similar points, claiming the clinical data show that if “100 people who are sick with COVID-19, 35 would have been saved because of the administration of plasma.” Hahn said the improvement represents “a pretty substantial clinical benefit.”
However, other people, including the anonymous FDA staffer who reviewed the EUA request, were far more equivocal about the evidence. The FDA reviewer said plasma “may be effective in the treatment of COVID-19,” adding that “it is reasonable to believe that the known and potential benefits of [the intervention] outweigh the known and potential risks.”
The review never explicitly cites the 35% survival improvement figure claimed by Azar and Hahn but the Assistant Commissioner for Media Affairs at FDA later took to Twitter to explain the data point is based on a comparison of patients in a Mayo Clinic trial who received high and low titer plasma.
The Mayo Clinic study was not a randomized placebo-controlled trial and, in the researchers’ own words, was designed to assess safety and “perform an exploratory analysis for potential signals of efficacy.” The 35% figure came from a post-hoc subgroup analysis.
In the trial, the 30-day mortality rate among patients who received plasma within three days of diagnosis was 21.6%. The mortality rate rose to 26.7% in patients who received plasma later in their disease progression.
The willingness of the heads of the FDA and HHS to tout the effect of plasma on survival despite the limitations of the data drew criticism from people including Scripps Research Translational Institute director Eric Topol.
“Outrageous to listen to [Trump, Azar and Hahn] claiming a 35% improved survival in an observational preprint study compared [with] late-treated patients. There's no evidence to support any survival benefit,” wrote Topol on Twitter.
Hahn later used Twitter to state some of the criticism he received “is entirely justified,” adding that he should have said “the data show a relative risk reduction not an absolute risk reduction.” The mea culpa failed to satisfy many critics.
The FDA awarded the EUA against a backdrop of concerns that it will come under political pressure to approve COVID-19 drugs and vaccines before seeing sufficient evidence of their safety and efficacy. Over the weekend, the Financial Times reported Trump is considering pushing for an EUA for AstraZeneca’s AZD1222 to ensure a COVID-19 vaccine is available before the November election.
Trump sees things differently, arguing on Twitter that the FDA is part of a “deep state” plot to delay the development of COVID-19 drugs and vaccines. The President framed the earlier hold on the plasma EUA as part of the same narrative.
“I think that there are people in the FDA and actually in your larger department that can see things being held up and wouldn’t mind so much. That’s my opinion — a very strong opinion. And that’s for political reasons,” said Trump.