A Narrative Review of the Clinical Practicalities of Bamlanivimab and Etesevimab Antibody Therapies for SARS-CoV-2

Abstract

The severity of coronavirus disease 2019 (COVID-19) ranges from mild to death, with high morbidity and mortality rates reported amongst a vulnerable subset of patients termed high risk. While vaccines remain the primary option for COVID-19 prevention, neutralizing monoclonal antibodies (mAbs), such as bamlanivimab and etesevimab, have been shown to benefit certain subpopulations after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unlike vaccine-derived immunity that develops over time, administration of neutralizing mAbs is an immediate and passive immunotherapy, with the potential to reduce disease progression, emergency room visits, hospitalizations, and death. Bamlanivimab alone and together with etesevimab hold emergency use authorizations in several countries globally, with countries increasingly transitioning to the use of bamlanivimab and etesevimab together and other authorized mAbs on the basis of their evolving variant landscape, regulatory authorizations, and access to drugs. The current guidelines for the administration of bamlanivimab alone or together with etesevimab are informed by an iterative process of testing and development. Herein the rationale for these guidelines is provided by sharing the learnings that have been gathered throughout the development process of these mAbs. In addition, this review addresses the most common clinical questions received from health care professionals (HCPs) and patients regarding indicated population, dose, use with other medications and vaccines, duration of protection, and variants in clinical practice. As prevalence of SARS-CoV-2 variants can differ by country and state, prescribing HCPs should consider the prevalence of bamlanivimab and etesevimab resistant variants in their area, where data are available, regarding potential efficacy impact when considering treatment options.Trial Registration: ClinicalTrials.gov identifier: NCT04427501; NCT04411628; NCT04497987; NCT04634409.

Keywords: Bamlanivimab; COVID-19; Clinical; Etesevimab; Health care practitioners; Monoclonal antibodies; SARS-CoV-2; Treatment.

Fig. 1

BLAZE-1 phase 2/3 study design to evaluate the efficacy of bamlanivimab alone and together with etesevimab in ambulatory participants with mild to moderate COVID-19 illness. Doses of bamlanivimab and etesevimab presented in brackets. N number of patients in cohort

Fig. 2

A timeline of the clinical development of bamlanivimab alone and together with etesevimab, including key milestones. EUA emergency use authorization, EMA European Medicines Agency, CHMP EMA’s human medicines committee, HCP health care providers

Fig. 3

Overview of high-risk criteria used to determine patient eligibility for treatment of mild-to-moderate COVID-19 with bamlanivimab and etesevimab together