The FDA and Trump has approved yesterday the emergency use authorization of convalescent plasma for treatment of COVID-19 patients. A recent Stanford study gives a fresh new perspective on this potential treatment for the coronavirus.
A day after publicly claiming America’s drug regulatory agency was playing political games with a potential blood-based treatment for Covid-19, President Donald Trump on the eve of the Republican National Convention said the Food and Drug Administration approved an emergency use authorization to use so-called convalescent plasma to treat hospitalized Covid patients.
But real answers about the use of the experimental treatment against the disease that has infected 5.7 million Americans and killed nearly 177,000 may rely on a study launched last week and centered at Stanford University.
The 600-person, Stanford-led study at 50 sites around the U.S. has been in the works since April but it took four months to develop clinical trial guidelines and get the research greenlighted by the FDA, Dr. Kevin Schulman, a Stanford medicine professor and research director, said.
Convalescent plasma taps the yellowish liquid part of blood — rich with Covid-fighting antibodies in people who have been infected with the virus — that is transfused in others to elicit an immune system response.
It’s not a quick process: A patient takes four to five days to develop an antibody response, which is most robust after seven to 10 days, but to stop an infected person from spreading the virus, they must be isolated for 10-14 days. So plasma typically is collected after 28 days to ensure that the virus is cleared and the blood contains the highest titer, or concentration, of Covid-specific neutralizing antibodies.
The emergency use authorization, or EUA, granted Sunday is based on an “expanded access” program, overseen by the Mayo Clinic and involving tens of thousands of hospitalized Covid patients not yet requiring a ventilator. Data from a small number of those patients indicated that patients who received plasma with a higher titer of relevant antibodies could have a lower risk of death.
But many scientists Sunday questioned the retrospective analysis of anecdotal evidence, which was hyped by Trump and offered few scientific certainties.
An expanded access, or compassionate use, program is not a clinical trial, but is designed to give the sickest of the sick a better chance to use experimental therapies.
Just two weeks ago, Schulman said, he treated a Covid patient with convalescent plasma at Stanford Hospital who required oxygen and was taking remdesivir, a drug with an EUA from Foster City-based Gilead Sciences Inc. (NASDAQ: GILD). The patient went home after a couple of days.
Did that patient get better from the remdesivir, because the convalescent plasma, the combination of the two or from their body simply generating enough neutralizing antibodies over time to fight off the virus? What’s more, Schulman said, because the EUA isn’t based on a formal, randomized, placebo-controlled trial, researchers still don’t know the right titer of antibodies to give in a convalescent plasma dose, when to give a dose, how many doses to give and whether the therapy is safe.
“There’s a big history of being fooled by non-randomized trials,” Schulman said. “These observational studies are important but not (definitive).”
The Stanford study, funded by the federal Biomedical Advanced Research and Development Authority, aims to get an answer as early as this fall from patients not yet requiring hospitalization. It will split patients into two groups — one that receives convalescent plasma and another that receives an injection of saline with a multivitamin — and tracks them for 30 days.
Plasma is an old treatment — it was used to treat Ebola virus, Spanish flu patients after World War I and by the military for measles — and studies of convalescent plasma in Covid patients have shown encouraging trends in China and the United States, Schulman said. One trend, he said, points to using it earlier in the disease, before the virus sets off the “cytokine storm” that damages organs and can lead to death; another suggests that patients who receive plasma with a higher titer of antibodies tend to recover better.
But, Schulman said, “We still don’t know if plasma benefits people.”
Part of the problem, researchers say, is that there has been no national strategy toward generating definitive data. If the Stanford study with its sites stretching from California to Florida and from Michigan to Texas, had started in April, it would have had data in May, Schulman said.
“We all want this convalescent plasma to work. I think it is going to work,” said Dr. Warner Greene, director of the Center for HIV Cure Research at the Gladstone Institutes, an affiliate of the University of California, San Francisco, and the founding director of Gladstone’s virology and immunology institute.
The FDA, which reportedly had been convinced to delay an EUA after National Institute of Allergy and Infectious Diseases chief Tony Fauci, National Institutes of Health Director Francis Collins and others argued that clinical data was too weak, said Sunday it will allow doctors to use convalescent plasma in hospitalized patients.
EUAs are not FDA approvals but are used to accelerate access to treatments. Gilead’s remdesivir received an EUA in early May, and the company now is seeking full FDA approval. The FDA had earlier this spring granted an EUA for hydroxychloroquine — a generic malaria and lupus drug whose use for Covid was championed by President Trump — but later withdrew that authorization when safety problems and questions about its effectiveness emerged in more rigorous studies.
Convalescent plasma is one of the therapies researchers have delved into since the coronavirus emerged in China in December and then caught fire in Europe and the United States, which now accounts for more than one in five of Covid deaths worldwide.
But companies and researchers in the Bay Area also have been exploring therapeutic antibodies, repurposing drugs that appear to hold off the inflammatory cytokine storm and other approaches to stopping or treating coronavirus infections.
Stocks to watch this week
- Sonnet BioTherapeutics (SONN)
- Kamada (KMDA)
- ThermoGenesis Holdings (THMO)
- T2 Biosystems (TTOO)
- Liminal Biosciences (LMNL)
- XBiotech (XBIT)
- Takeda Pharmaceuticals (TAK)
- Cerus (CERS)
- ADMA Biologics (ADMA)
