By Daniel R. Lucey M.D., MPH, FIDSA
In assessing any potential benefit on symptom duration or viral load reduction, let alone “cure,” it is important to know whether non-hospitalized patients are already making their own antibodies against SARS-CoV-2 at the time they receive the Regeneron ”REGN-COV2 cocktail” of two monoclonal antibodies against the spike protein of SARS-CoV-2.
If patients lack their own antibodies, then they are reported to be more likely to benefit (but see p-values in the press release below) in terms of shorter duration of symptoms and reduction in viral load, than if they already have started making their own antibody (“seropositive”).
On Sept. 29 Regeneron issued a press release that was focused only on non-hospitalized patients (none of whom were reported also to be on remdesivir or dexamethasone). It reported a descriptive analysis of REGN-COV2 in “the first 275 patients.” Equal numbers of persons (randomized 1:1:1 and thus approximately 91 or 92) received either placebo, low dose (2.5 grams IV once) monoclonal antibody, or high dose (8 grams IV once) monoclonal antibody.
Of note, “Patients were prospectively characterized prior to treatment by serology tests to see if they already generated antiviral antibodies on their own and were classified as seronegative (no measurable antiviral antibodies) or seropositive (measurable antiviral antibodies). Approximately 45% of patients were seropositive, 41% were seronegative and 14% were categorized as “others due to unclear or unknown serology status.”
Importantly, most of any benefit on symptoms or viral load were in seronegative patients:
“Seropositive patients had much lower levels of virus at baseline, and rapidly achieved viral loads approaching lowest levels quantifiable (LLQ), even without treatment (my boldtype for emphasis). In contrast, seronegative patients had substantially higher viral levels at baseline, and cleared virus more slowly in the absence of treatment.”
“In the untreated (placebo) patients, seropositive patients had a median time to alleviation of symptoms of 7 days, compared to seronegative patients who had a median time to alleviation of symptoms of 13 days”.
“Among seronegative patients, median time to symptom alleviation (defined as symptoms becoming mild or absent) was 13 days in placebo, eight days in high dose (p =0.22), and six days in low dose (p=0.09)”.
“There were a small number of medically attended visits given that most non-hospitalized patients recover well at home”. “10 of the 12 medically-attended visits (defined as hospitalizations, or emergency room, urgent care or telemedicine visits for COVID-19) occurred in patients who were seronegative at baseline” (thus, zero, one or two such visits occurred in seropositive patients or in the “other” patients with unknown or unclear serology status at baseline.
On Wednesday, Regeneron posted a “Statement on REGN-COV2 Emergency Use Authorization Request.”
How will FDA make its decision on this request for an EUA? Will it convene a meeting of outside expert advisors? In what time frame will the FDA announce its decision?
A second US company also requested an EUA for its monoclonal (single) antibody Wednesday.
Will the FDA make its decision on both companies’ requests at the same time?
Daniel Lucey, M.D. MPH, FIDSA, FACP, is an infectious diseases physician and adjunct professor of infectious diseases at Georgetown University Medical Center, a senior scholar at the Georgetown University O’Neil Institute, Anthropology Research Associate, Smithsonian Museum of Natural History and a member of the Infectious Diseases Society of America Global Health Committee.He has served as a volunteer medical responder to outbreaks that included the West Africa Ebola crisis. He has collected information on outbreaks starting in 2001 with cases of anthrax in 2001, and including smallpox vaccination 2002, SARS 2003, H5N1 Flu 2004, MERS in 2013, and Ebola in April, 2014, He has gathered, and updated information on the spread of the coronavirus here since Jan. 6.