Neutralizing anti-spike monoclonal antibodies for COVID-19 in vulnerable populations: lessons learned and future directions

ABSTRACT

Introduction

Anti-spike monoclonal antibodies were highly effective for prophylaxis and early treatment of mild-to-moderate COVID-19 in high-risk populations.

Areas covered

This article reviews the clinical trials that led to the emergency use authorization of bamlanivimab with or without etesevimab, casirivimab and imdevimab, sotrovimab, bebtelovimab, and tixagevimab and cilgavimab in the United States. Clinical trials provided evidence that anti-spike monoclonal antibodies were highly effective, if administered early, for the treatment of mild-to-moderate COVID-19 among high-risk patients. Clinical trials also provided evidence that certain anti-spike monoclonal antibodies were highly effective when given as pre-exposure or post-exposure prophylaxis among high-risk individuals, including immunosuppressed populations. The evolution of SARS-CoV-2 resulted in spike mutations that conferred reduced susceptibility to anti-spike monoclonal antibodies.

Expert opinion

Anti-spike monoclonal antibodies for treatment and prevention of COVID-19 resulted in therapeutic successes that resulted in reduced morbidity and improved survival among the high-risk populations. Lessons learned from their clinical use should guide the future development of durable antibody-based therapies. A strategy that will preserve their therapeutic lifespan is needed.

KEYWORDS:

• bamlanivimab
• bebtelovimab
• casirivimab
• cilgavimab
• etesevimab
• imdevimab
• sotrovimab
• tixagevimab

Article highlights

• Anti-spike monoclonal antibodies were highly effective for pre-exposure and post-exposure prophylaxis to prevent coronavirus disease−2019 in high-risk exposed persons.

• Anti-spike monoclonal antibodies were highly effective as early treatment of mild-to-moderate COVID-19 and prevented the progression to severe disease in high-risk populations.

• This article comprehensively reviews and summarizes the controlled clinical trials that led to the emergency use authorization of bamlanivimab with or without etesevimab, casirivimab and imdevimab, sotrovimab, bebtelovimab, and tixagevimab and cilgavimab in the United States.

• The evolution of SARS-CoV-2 resulted in spike mutations that conferred reduced susceptibility to anti-spike monoclonal antibodies.

• Lessons learned from the clinical use of anti-spike monoclonal antibodies will guide the future development of more durable antibody-based therapies, incorporating strategies that will preserve their therapeutic lifespan.

Declaration of Interest

RR Razonable has received research grants (to his institution) from Roche, Regeneron and Gilead. He is a member of the Endpoint Adjudication Committee for Allovir and a member of the Board of Directors, American Society of Transplantation. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have been investigator in mAbs clinical trials for COVID-19. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was funded by intramural grant from the Mayo Clinic. The institution did not have any role in the conceptualization, data retrieval, drafting and review, or approval of this manuscript for submission.