FDA Issues Emergency Approval of Convalescent Plasma for COVID-19

The FDA has issued an Emergency Use Authorization (EUA) for investigational convalescent plasma for the treatment of COVID-19 in hospitalized patients. Authorization for COVID-19 Convalescent Plasma (CCP) is supported by four lines of evidence:

  • history of convalescent plasma for respiratory coronaviruses
  • evidence of preclinical safety and efficacy in animal models
  • published studies of the safety and efficacy of CCP
  • data on safety and efficacy from the National Expanded Access Treatment Protocol (EAP) sponsored by the Mayo Clinic

In an analysis of more than 35,000 patients enrolled in the Mayo Clinic study who received convalescent plasma, researchers found that the treatment had a marked effect on mortality in severe cases of COVID-19. Patients who received transfusions within 3 days of diagnosis had a 7-day death rate of 8.7%, while patients who were treated 4 or more days after diagnosis had a mortality rate of 11.9%. Similar findings were reported in the 30-day mortality analysis: 21.6% versus 26.7%. The study lacked a placebo group, however, making it unclear if other confounding factors affected patient outcome.

In a press conference announcing the decision, FDA Commissioner Stephen Hahn, MD, stated that, based on anecdotal data from Mayo Clinic, 35 out of 100 patients with COVID-19 “would have been saved because of the administration of plasma.”

The scientific community quickly questioned how Dr. Hahn arrived at that number, prompting him to walk back the statements of convalescent plasma’s effectiveness the next day.

“I have been criticized for remarks I made Sunday night about the benefits of convalescent plasma,” he wrote on Twitter. “The criticism is entirely justified. What I should have said better is that the data show a relative risk reduction not an absolute risk reduction.”

Dr. Hahn appeared to be referencing data from a smaller subgroup of patients who received plasma with higher IgG antibody levels: The pooled relative risk of 7-day mortality among 80 patients who received high IgG plasma (>18.45 S/Co) was 0.65, compared with patients who received plasma units with lower levels of IgG antibodies.

Others speculated whether the FDA, under pressure from President Donald Trump, rushed the decision. A week prior to the approval, a group from the NIH, including Director Francis S. Collins, MD, PhD, and Anthony S. Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases, staged an intervention on the authorization of plasma therapy, citing the need for randomized controlled trials to determine if the treatment is effective. President Trump, however, criticized the agency’s hold on authorizing the treatment, accusing the FDA of acting with politically motivated interests and withholding the decision until after the upcoming presidential election.

In a statement, the FDA wrote that the EUA is “not intended to replace randomized clinical trials and facilitating the enrollment of patients into any of the ongoing randomized clinical trials is critically important for the definitive demonstration of safety and efficacy of COVID-19 convalescent plasma.”

Sources: STAT, August 23, 2020; The New York Times, August 19, 2020; Joyner MJ, Senefeld JW, et al. Effect of convalescent plasma on mortality among hospitalized patients with COVID-19: initial three-month experience. medRxiv preprint. August 12, 2020; The New York Times, August 24, 2020.