White House coronavirus adviser Dr. Anthony Fauci knows it would be illogical, and he said as much, to base anything on a sample size (N) of one. Still, Fauci suspects an experimental antibody injection might very well have been behind U.S. President Donald Trump’s apparent turnaround from COVID-19.
“Whether or not it was that that got him better, I’m strongly suspicious that it was,” Fauci told CNN. “Whenever you have an N equals 1, you can’t prove it, but I think that the monoclonal antibody made a difference.”
Trump received an eight-gram dose of the unlicensed antibody cocktail made by New York-based biotech company Regeneron on Friday. The president, his doctors said, completed the infusion “without incident.” Trump is also being treated with the anti-viral drug, Remdesivir, as well as dexamethasone, a cheap steroid shown to reduce deaths in people severely sick with COVID-19.
Two weeks ago, Regeneron announced, via press release, that its investigational drug, REGN-COV2, reduced viral levels and improved symptoms faster than placebo in 275 people infected with COVID-19 who were mildly to moderately ill, but not sick enough to be hospitalized. The Sept. 29 press release, the company told the National Post Tuesday, “covers the only data we have in humans thus far — we’ll be sure to share more once we have it.” Regeneron is also testing its COVID antibody injection in hospitalized people. There are no human studies in Canada at the moment.
Eli Lilly has also launched human trials of its own antibody therapies.
The logic behind the approach “is really quite simple”, said Ottawa critical care physician Dr. James Downar. It involves mass-producing antibodies against a target virus or infection, in this case the SARS-CoV-2 virus that causes COVID-19.
Scientists first search for the most potent antibodies. In their case, the Regeneron team sifted through thousands of “fully-human” antibodies, as described by the company, produced by transgenic, or humanized mice exposed to SARS-CoV-2, as well as antibodies identified from humans who have recovered from COVID-19.
They focused on two antibodies that bind to the spike protein that adorns the COVID-19 virus the strongest. It’s these pointy proteins that the virus uses like a skeleton key to slip inside human cells. The antibodies glob on to the proteins, blocking the virus from entering cells and causing infection.
The antibodies are mass-produced in other mice, collected, concentrated down and put into a drug preparation that can be injected into humans.
Antibodies can also be harvested from immune cells collected from the plasma of people exposed to SARS-CoV-2. “You take those cells out and put them in a dish or a flask and ‘immortalize’ them — make them kind of live forever and replicate forever,” producing antibodies over and over again, said Dr. Donald Arnold, a hematologist at McMaster University in Hamilton.
Much hope is being pinned on monoclonal antibodies “because even though they’re expensive and they’re not going to make a gajillion doses, they could make a big difference in the whole landscape of the pandemic,” Eric Topol, founder and director of the Scripps Research Translational Institute in La Jolla, California, told STAT.
Reducing viral load is probably a good thing, “but we don’t know if that actually improves outcomes,” Downar, of The Ottawa Hospital said. “There are lots of things that can impair viral replication that don’t actually change outcome. Because by the time you get an actual symptom, the virus has spread a long way and is already doing a lot of damage.
“It’s entirely possible that by the time you’re giving it, you’re giving it too late.”
That Trump got something wholly experimental has raised eyebrows, but monoclonal antibodies are used throughout medicine for treating infectious diseases, autoimmune conditions and lymphomas.
“The short answer is: great promising therapy but we’ll need to see better data,” Downar said.
The downside? It’s challenging and expensive to make. It’s laborious, time-consuming, and monoclonal antibody therapy can cost thousands of dollars per person treated.
As well, any antibody therapy has a potential to trigger an exaggerated or haywire immune or inflammatory response that, in rare cases, could cause damage to multiple organs, Downar said.
“If you’re using it in situations where the person doesn’t have an adequate immune response and the insult, the infection, is causing a lot of damage, then there’s good logic to think this might be effective,” he said.
It’s hard to say what helped Trump. The science is strongest for dexamethasone, a ubiquitous, inexpensive steroid.
“It’s impossible to know,” said Arnold, a professor and one of the principal investigators for a large convalescent plasma trial happening in Canada.
“The other piece is that, as far as I can tell, Trump had fairly mild symptoms, certainly not enough to qualify him to be hospitalized for a prolonged period of time or to require oxygen for a prolonged period of time. For many people, if they had those symptoms, they would probably not be hospitalized —they would be treated in the clinic, and a lot of them would get better on their own, anyway.”
“Really hard to know, for all of those reasons, if this treatment made any difference in this particular case.”
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