Conclusion
Emergency Use Authorization from the U.S. Food and Drug Administration
is currently being sought for two monoclonal antibody therapies for
COVID-19, with others under development. It has been conclusively
demonstrated that soluble ACE2 decoys can be engineered to rival the
affinities of monoclonal antibodies, and provided IgG fusions confer
desirable pharmacokinetics in humans, there is no reason to expect
soluble ACE2 decoys cannot be as effective as monoclonals in reducing
viral load in patients. Anti-SARS-CoV-2 monoclonals have received a
preferential regulatory environment for clinical advancement due to an
in-depth understanding of antibody biochemistry, pharmacokinetics and
general toxicology. Decoy receptors will always come with additional
risks related to immunogenicity and safety, and the outstanding question
for the community is whether they provide truly unique benefits that
outweigh those risks. The advantages of soluble ACE2 are its breadth
against SARS-associated coronaviruses and its potential for alleviating
COVID-19 symptoms through intrinsic enzymatic activity. We believe these
advantages justify continued efforts towards advancing these proteins to
the clinic.