By Daniel R. Lucey M.D., MPH, FIDSA
On Oct. 7, the U.S. Food and Drug Administration received requests for Emergency Use Authorization for monoclonal antibodies from two companies (Regeneron and Eli Lilly), but has not yet announced any public meetings of its Antimicrobial Drugs Advisory Committee to advise on either general issues or specific requests for EUA for monoclonals to treat or prevent COVID-19.
Given only preliminary data on any clinical benefit, as well as logistical, financial, and political issues (e.g., the President’s treatment with one of these products), now is the time for FDA to announce a public meeting on monoclonals for COVID-19 treatment and prevention.
In contrast, on Oct. 22, FDA will convene a public meeting of its Vaccine Advisory Committee to discuss general issues related to anticipated future COVID-19 vaccine EUA requests, even though no such request has yet been received.
As emphasized on Science Speaks, Oct. 8, the data in the Sept. 29 press release by Regeneron only for non-hospitalized patients receiving their monoclonal REGN-COV2 reported that persons who already had some of their own antibodies to the virus (“seropositive”) responded less well than those who did not (“seronegative”).
If FDA grants an EUA for REGN-COV2 should non-hospitalized patients have a rapid antibody test performed and then only seronegative persons offered REGN-COV2? If so, what rapid antibody test(s) should be used given that time will be of the essence to decide whether or not to offer REGN-COV2?
Moreover, would an EUA apply only for low dose (2.4 grams) or only high-dose (8 grams) of REGN-COV2?
On Oct. 7 the President’s physician stated that the President tested negative for his own IgG antibodies “late Thursday night.”
Even seronegative non-hospitalized patients, however, were reported in the Regeneron Sept. 29 press release not to reach statistical significance in terms of median time to symptom alleviation:
“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)”.
Furthermore, no statistically significant benefit was reported in terms of decreasing hospitalization rates for non-hospitalized patients receiving either high dose or low dose REGN-COV2, whether seropositive or seronegative beforehand.
Importantly, hospitalization was only 1 of 4 types of “medically-attended visits” that were presented in their press release. The four were: “hospitalizations, or emergency room, urgent care or telemedicine visits for COVID-19.”
In the seropositive group (45% of 275 patients) a total of only two “medically-attended visits” were reported. In the seronegative group (41% of 275 patients) only a total of 10 “medically-attended visits” occurred with an unspecified number occurring in each of the three subgroups of placebo, low-dose, and high-dose REGN-COV2.
Now is the time for the FDA to announce a public meeting on monoclonals for COVID-19 treatment and prevention and an independent outside advisory committee of well-known experts such as the Antimicrobial Drugs Advisory Committee.
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.