Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
This afternoon, the White House announced that President Donald Trump had received an experimental antibody treatment after a test revealed he was infected with SARS-CoV-2. He reportedly has mild COVID-19 symptoms, including fever and congestion, and he was transferred to Walter Reed National Military Medical Center later in the day.
What is the antibody cocktail that President Trump received?
It’s a combination of two antibodies directed against a key protein of the virus that causes COVID-19, SARS-CoV-2. They bind to a region on the main surface protein, spike, that helps the virus attach to a receptor on human cells called ACE2. The targeted region is dubbed the receptor binding domain. One antibody comes from a human who had recovered from a SARS-CoV-2 infection; a B cell that makes the antibody was harvested from the person’s blood and the genes for the immune protein isolated and copied. The other antibody is from a mouse, which was engineered to have an immune system, that had the spike protein injected into it.
Is there any data showing that that the cocktail works and is safe?
Experiments in both golden hamsters and rhesus macaque monkeys that intentionally were infected with SARS-CoV-2 showed that the cocktail could reduce viral levels and disease pathology.
Regeneron, the maker of the cocktail, earlier this week presented preliminary data from its ongoing clinical trial in people who tested positive for SARS-CoV-2 but were asymptomatic or, in the most extreme cases, had moderate disease—a group that would appear to mirror President Trump’s current condition. No serious safety concerns surfaced, and the treatment reduced viral load and shortened symptomatic disease in patients who did not have SARS-CoV-2 antibodies at the trial’s start. It’s unclear whether the treatment can prevent severe disease, but there were hints that it might: Participants who received a placebo had more medical visits.
A separate trial is assessing the impact of the treatment on hospitalized COVID-19 patients, but Regeneron has yet to report any results from that study.
Do the preliminary clinical trial data match the President’s treatment scheme?
Not exactly. The President received an 8-gram infusion of the treatment. Regeneron’s data showed that a 2.4-gram infusion worked as well as the higher dose at reducing SARS-CoV-2 levels in people. This was widely seen as good news because monoclonals are difficult and expensive to produce, and a lower dose means that more people ultimately can receive it.
Why did the President receive the higher dose of the antibodies?
Likely out of “an abundance of caution” by the President’s medical team, says George Yancopoulos, the co-founder and chief scientific officer of Regeneron. Yancopoulos does not directly know why the President’s physicians chose to use 8 grams, but says the company’s data indicate there’s “very, very limited risk” that the antibodies will cause harm at either dose. The higher dose might last longer, he said, and at some time points in the company’s study, Regeneron did see “trends” suggesting that the higher dose more powerfully beats back the virus—the company used the amount of viral genetic material found with nose swabs as a proxy for SARS-CoV-2 levels in the entire body.
“If I had to treat one patient, I’d give the high dose,” says Yancopoulos. “From a societal point of view and the need to treat as many people as possible, I’d give the lower dose.”
Did the President match the patients in the study who benefited from the treatment?
The Regeneron study found that the treatment only worked in people who did not have SARS-CoV-2 antibodies at the start of the study. It also worked best in people who had higher levels of the virus. Whether the President had those antibodies and a high viral load has not been made public. “I couldn’t speculate because it has to do with an individual patient,” says Yancopoulos.
The memorandum from the President’s physician said Trump was receiving “Regeneron’s polyclonal antibody cocktail.” Are these antibodies “polyclonal”?
No. The treatment consisted of two monoclonal antibodies—meaning each was produced by making identical copies, or clones, of an antibody gene in a single B cell. Polyclonal antibody cocktails refer to antibodies made by mixtures of B cells.
What was the regulatory mechanism that allowed the President to receive the experimental Regeneron antibodies?
The antibodies are typically only available to people who participate in clinical trials. Trump theoretically could have enrolled in the ongoing treatment study that reported preliminary data this week, but that trial randomly assigns half the participants to receive the antibodies; the other half serve as a control group and receive infusions of an inactive placebo. A U.S. Food and Drug Administration (FDA) regulation called “expanded access”—technically known as 21 CFR 312.310—allows physicians to request “compassionate use” of experimental treatments through an “investigational new drug” pathway used for individual patients or for emergencies. “These are designed to be used in these rare and special circumstances,” says Yancopoulos. “This is not the first time we’ve done compassionate use for these monoclonal antibodies. This is not a mechanism for widespread distribution.”
Could Regeneron’s monoclonal antibody treatment become more widely available through the FDA’s Emergency Use Authorization (EUA) pathway?
Yes. Both Regeneron and Lilly, which similarly reported encouraging preliminary clinical trial data last month from a single SARS-CoV-2 monoclonal antibody, are discussing the possibility of an EUA with the FDA. Lilly reported signs that its antibody reduced the need for hospitalization, but as with Regeneron, too few participants have so far become seriously ill to reach a convincing conclusion to this critical question.
Is the President receiving any other COVID-19 treatments?
The statement released today by the President’s physician said that in addition to the antibodies, Trump “has been taking zinc, vitamin D, famotidine, melatonin and a daily aspirin.” That wording leaves unclear whether he was taking those substances before his diagnosed infection. Notably, the statement does not indicate if Trump was or is taking hydroxychloroquine, the antimalarial he controversially pushed as a COVID-19 treatment.
Famotidine has been suggested to be a treatment for COVID-19, but it’s also a popular heartburn remedy, sold widely under the name Pepcid. A clinical trial testing it in hospitalized COVID-19 patients in New York was not able to recruit enough patients to properly evaluate its impact. The Feinstein Institutes for Medical Research, which initiated that trial, released a statement today citing evidence it was helpful for COVID-19 but also saying, “We have yet to prove [famotidine’s] efficacy.” The institute says it’s “eagerly awaiting” FDA approval of a trial that will evaluate whether famotidine can help people who are not hospitalized.