Sotrovimab: A Review of Its Efficacy against SARS-CoV-2 Variants

Abstract

Among the anti-Spike monoclonal antibodies (mAbs), the S-309 derivative sotrovimab was the most successful in having the longest temporal window of clinical use, showing a high degree of resiliency to SARS-CoV-2 evolution interrupted only by the appearance of the BA.2.86* variant of interest (VOI). This success undoubtedly reflects rational selection to target a highly conserved epitope in coronavirus Spike proteins. We review here the efficacy of sotrovimab against different SARS-CoV-2 variants in outpatients and inpatients, discussing both randomized controlled trials and real-world evidence. Although it could not be anticipated at the time of its development and introduction, sotrovimab’s use in immunocompromised individuals who harbor large populations of variant viruses created the conditions for its eventual demise, as antibody selection and viral evolution led to its eventual withdrawal due to inefficacy against later variant lineages. Despite this, based on observational and real-world data, some authorities have continued to promote the use of sotrovimab, but the lack of binding to newer variants strongly argues for the futility of continued use. The story of sotrovimab highlights the power of modern biomedical science to generate novel therapeutics while also providing a cautionary tale for the need to devise strategies to minimize the emergence of resistance to antibody-based therapeutics.

From Detection to Protection: Antibodies and Their Crucial Role in Diagnosing and Combatting SARS-CoV-2

“…A recent study demonstrated an excellent clinical response in immunocompromised patients with prolonged COVID-19 by combining two antivirals (mainly remdesivir and nirmatrelvir/ritonavir) with mAbs [287]. Thus, employing a blend of mAbs alongside concurrent small-molecule antiviral treatments, such as protease and replicase inhibitors, can mitigate the risk of resistance emergence, ensuring more robust and lasting efficacy against evolving viral strains [146,288]. However, the elevated risks associated with safety concerns, potential drug interactions, and adverse effects of these therapies may account for a portion of the limited number of subjects undergoing clinical trials for COVID-19 at this time.…”