- President Donald Trump late Sunday announced that the Food and Drug Administration has issued an emergency approval for the use of antibody-rich blood samples from recovered COVID-19 patients — what's known as convalescent plasma — to treat people hospitalized with coronavirus disease.
- The FDA had reportedly been set to clear convalescent plasma for emergency use earlier this month before top NIH officials intervened, citing a lack of rigorous data thus far supporting its use. Convalescent plasma, used for a century to treat certain infectious diseases — and other respiratory viruses — hasn't yet proven it can help treat COVID-19 in a randomized, placebo-controlled clinical trial. Trump, however, has increasingly publicly pushed for its use.
- The emergency nod is the third the agency has given to a COVID-19 treatment, following similar decisions for the antiviral remdesivir and the generic malaria pill hydroxychloroquine. As with hydroxychloroquine, whose EUA was later revoked, the emergency clearance for convalescent plasma is likely to stir controversy since its potential benefits are unclear.
A weekend that began with President Trump accusing the FDA on Twitter of stalling the progress of treatments for COVID-19 ended with a press conference in which Trump congratulated agency commissioner Stephen Hahn for issuing a new emergency approval.
That so-called emergency use authorization, or EUA, is for convalescent plasma, which comes from donor samples of blood from COVID-19 patients and includes the antibodies their bodies formed to fight off infection with SARS-CoV-2.
An EUA isn't a standard drug approval, but a tool regulators can use to boost access to a treatment when a public emergency is in place without waiting for the typical amount of supportive evidence. The requirements are that a treatment “is reasonable to believe that the product may be effective” and “the known and potential benefits outweigh the known and potential risks.”
"In the independent judgment of experts and expert scientists at FDA who have reviewed the totality of data," Hahn said at a Sunday evening press conference, "COVID-19 convalescent plasma is safe and shows promising efficacy, thereby meeting the criteria for an emergency use authorization."
Yet the FDA's decision is unusual, because the most significant underlying evidence to support the use of convalescent plasma does not come from a placebo-controlled clinical trial, the gold standard of scientific research.
Rather, the evidence cited by Trump, Hahn and HHS secretary Alex Azar at Sunday's press conference — what they referred to as a 35% improvement in survival — comes from an exploratory analysis of an expanded access program headed by the Mayo Clinic and sponsored by the FDA. That analysis, which began in April, compared the effects of the plasma-derived treatment on 35,322 patients when transfused at different time points. It wasn't designed to definitively prove whether the treatment works against COVID-19.
In that analysis, the Mayo clinic found that that the seven-day death rate of severe COVID-19 patients who got convalescent plasma within three days of diagnosis was 8.7 percent, compared to 11.9 percent for those who got it four or more days after diagnosis. The results appeared to be more pronounced in patients whose transfusions contained higher levels of antibodies.
Hahn, pointing to those results, indicated that the study had proven that if 100 people were sick with COVID-19, 35 of them would have been saved by convalescent plasma.
"That's a pretty substantial clinical benefit," Hahn said at the press conference.
Late Monday night, Hahn clarified his remarks. The criticism was “entirely justified,” he wrote on twitter. “What I said is the data show a relative risk reduction, not an absolute risk reduction,” he added.
“I personally could have done a better job and should have done a better job at the press conference explaining what the data show,” he said during a TV interview on Tuesday.
Still, the Mayo Clinic study, which hasn't been peer reviewed yet, was difficult to interpret since the trial didn't include a placebo arm. The data "provide signatures of efficacy" in hospitalized COVID-19 patients, wrote the study authors, and "may be informative" for treatment and the design of randomized clinical trials.
The New York Times reported last week that several top government health officials convinced the FDA to delay an emergency approval, citing concerns with the data. Trump, who has touted convalescent plasma as a "beautiful ingredient," claimed at the press conference that the delay was politically motivated.
Those circumstances, coupled with the shortcomings of the data, led some to question whether the agency was pressured by the White House to approve convalescent plasma. Hahn denied those allegations on twitter. “The decision was made by FDA careers scientists based on data submitted a few weeks ago,” he wrote.
In a statement announcing the approval, the FDA said that it is "reasonable to believe" that convalescent plasma "may be effective in lessening the severity or shortening the length of COVID-19 illness in some hospitalized patients." The memo explaining its decision, however, emphasized that "adequate and well-controlled randomized trials remain nonetheless necessary" to prove the worth of convalescent plasma and find would best benefit from treatment.
"We are going to continue to collect data," Hahn said at the press conference, referring to multiple ongoing, placebo-controlled tests in different disease settings. The FDA in June reversed an earlier emergency approval for hydroxychloroquine after data emerged suggesting it was "unlikely to be effective" against COVID-19.
Hospitals in the U.S. have already been using convalescent plasma to treat patients infected by the new coronavirus. The treatment has been used on more than 70,000 people infected with SARS-CoV-2, and more than 90,000 have been enrolled in the expanded access program as of mid-August. The emergency authorization by the FDA enables the U.S. government to help broaden access to the treatment.
"We've seen a great deal of demand for this," Hahn said. The emergency authorization "allows us to continue to meet the demand."