Liliana Elena Weimer, Cattari Giovanna, Fanales-Belasio Emanuele, Cuccuru Elena, Vidili Gianpaolo
Despite the challenges of outpatient administration and associated costs, monoclonal antibodies were a mainstay of the COVID-19 armamentarium from November 2020, when bamlanivimab first received US food and drug administration Emergency Use Authorization (EUA), through November 2022, when the bebtelovimab EUA was revoked.
Ideal qualities of treatments include effectiveness in preventing hospitalization and death, safety and tolerability for patients, easy administration in the outpatient environment, and cost-effectiveness. Monoclonal Antibodies (mAbs) that neutralize SARS-CoV-2 fit the safety and efficacy profile in early randomized clinical trials.
Monoclonal antibodies targeting the anti-SARS-CoV-2 Spike (S) protein are prescribed in high income countries to prevent severe disease in at risk patients. Although studies report efficacy as between 50% to 85%, global access is currently largely inequitable.
Multivariate omicron (B.1.1.529) and sub variant (BA.2 followed by BA.4 and BA.5) dominance has challenged the treatment landscape for mild to moderate disease, introducing considerable uncertainty on the efficacy of monoclonal antibodies and leading to changes to initial recommendations for some of them. Contemporaneously, oral, direct acting antivirals with a reported efficacy ranging from 30% (molnupiravir) to 89% to 90% (nirmatrelvir/ritonavir) have recently received conditional or emergency approval in some countries and been recommended in international guidelines such as the world health organization guidelines. S-217622, also known as ensitrelvir, a 3CL protease inhibitor that has been shown to significantly reduce the infectious viral load, is currently in phase 3 trials and waiting for emergency approval in Japan and should be submitted soon in China. The main purpose of this opinion paper is to highlight the possible strategies to optimize and protect current and future therapeutic options to treat the most vulnerable patients.