The FDA has authorized the use of plasma from people who have recovered from infection by the novel coronavirus as a treatment for hospitalized COVID-19 patients, a move widely perceived as influenced by political pressure given the lack of clear evidence of clinical benefit.
Treating patients with plasma—the water, salts, and proteins that make up the liquid part of blood in which blood cells and platelets are suspended—from those who have recovered from the infection is an approach that has been previously used to treat cases of other viral illnesses, including Ebola. The idea is that the antibodies generated by people who have been able to fight off the illness may be able to do the same in patients whose immune systems are struggling to do so.
In its memo Sunday, the FDA said the evidence in favor of COVID-19 convalescent plasma (CCP) indicated it “may be effective” against the virus—a criterion required to issue an emergency use authorization (EUA). The memo cited the history of its use against respiratory viruses; preclinical evidence of safety and efficacy as observed in animals; results from studies of the potential treatment, including two randomized controlled trials; and data from a Mayo Clinic-led expanded access program though which more than 70,000 patients have received plasma from COVID-19 survivors.
“It is reasonable to conclude that the known and potential benefits of CCP outweigh the known and potential risks of CCP for the proposed EUA,” the agency wrote.
The randomized controlled trials, conducted in the outbreak epicenter of Wuhan, China, and in the Netherlands, indicated CCP could be providing some clinical benefit. But both were stopped early, so it is unclear whether the findings were statistically significant, according to the agency.
“Adequate and well-controlled randomized trials remain necessary for a definitive demonstration of CCP efficacy and to determine the optimal product attributes and appropriate patient populations for its use,” its memo says.
The EUA announcement, made Sunday night, drew industry skepticism.
“We need to ensure the scientists at FDA are allowed to do their work, independently, and that FDA officials’ decisions are allowed to stand,” said Michelle McMurry-Heath, CEO of BIO, in a prepared statement. “The science, not politics, should drive these decisions.”
Reuters reported that the World Health Organization’s chief scientist, Soumya Swaminathan, called trial results to date “very low-quality evidence” as to the effectiveness of plasma against COVID-19.
“So we recommend that convalescent plasma is still an experimental therapy, it should continue to be evaluated in well-designed randomized clinical trials,” he said during a news conference.
In contrast, US health and human services secretary Alex Azar called the EUA “very happy news” and a “major advance.” He cited a 35 percent improvement in mortality among patients under 80 who were not intubated. But that difference was between a group of patients who received plasma containing a higher levels of antibodies and one that received plasma with a lower level of antibodies, not between a group that received plasma and a control group. The absence of a comparison with a control group makes the extent of clinical benefit, if any, unclear.
The Mayo Clinic program’s primary goal was to expand access to plasma, not to analyze its efficacy, the FDA memo notes. Rickey Carter, of Mayo Clinic Florida, on Aug. 1 said the study’s lack of randomization was primarily due to logistical issues.
“This was always thought of as a bridging study,” Carter said. “This was to generate some initial information, simplify some regulatory processes, [and] try to move the science of convalescent plasma forward as well as the treatment of COVID-19.”
Preliminary results from the Mayo Clinic study have been published on a pre-print server. The FDA authorization suggests dosing with a 200 mL CCP unit at first. Additional units may be given based on the physician’s judgement and a patient’s clinical response.
The authorization is the third the FDA has issued in relation to COVID-19. The first—also perceived as politically influenced given President Trump’s vocal support—was for chloroquine and hydroxychloroquine, medications used to prevent or treat malaria and, in the case of hydroxychloroquine, a range of autoimmune diseases. Emergency authorization is not the same as an approval, and it can be revoked if additional studies fail to demonstrate that a drug’s benefits outweigh its risks. That’s what happened with chloroquine and hydroxychloroquine.
In May, the agency issued an EUA for the experimental Gilead Sciences (NASDAQ: [[ticker:GILD]]) antiviral drug remdesivir, which in a randomized and double-blinded study conducted by the National Institute of Allergy and Infectious Diseases prompted faster patient recovery compared to a group that received a placebo.
Image: iStock/Bertrand Blay
