Emerging anti-spike monoclonal antibodies against SARS-CoV-2

ABSTRACT

Introduction

Anti-spike monoclonal antibodies (mAbs) were previously authorized for the prevention and treatment of COVID-19 in immunocompromised patients. However, they are no longer authorized in the U.S. due to their lack of neutralizing activity against current circulating SARS-CoV-2 Omicron variants.

Areas covered

We summarized the available data on emergent mAbs in the early stages of clinical development. Consistent with data on prior mAbs, these novel agents have been well tolerated and demonstrated a good safety profile in early clinical trials. Additionally, many of them have been engineered to ensure prolonged half-life and combined with other mAbs to overcome the potential for emerging resistant mutants. Interestingly, one of these agents has been evaluated using an inhaled route of administration, and another agent is being evaluated for treatment of long COVID.

Expert opinion

Although the available data of novel mAbs holds promise, we anticipate that these agents will face similar challenges encountered by prior authorized agents, including the continued evolution of SARS-CoV-2 and emergence of new escape mutations. Strategies to potentially mitigate this are discussed. Based on prior successful experience, immunocompromised patients will certainly benefit from the utilization of mAbs for the prevention and treatment of COVID-19; thus, we need to design potential interventions to ensure the sustained activity of these agents.

KEYWORDS:

• Adintrevimab
• AER001/AER002
• Anti-spike monoclonal antibodies
• AZD3152/AZD5156
• COVID-19
• CT-P63
• IBIO123
• VYD222

Article highlights

• Anti-spike monoclonal antibodies (mAbs) against SARS-CoV-2 were safe and highly effective therapies that improved outcomes in unvaccinated and immunocompromised patients with COVID-19.

• Previously authorized anti-spike mAbs are no longer available due to their lack of neutralizing activity against currently circulating SARS-CoV-2 variants.

• This article reviews the early clinical data on investigational and emerging anti-spike mAbs that are undergoing evaluation in clinical trials.

• Early data suggest that these novel anti-spike mAbs are safe and possess variable activity against newer SARS-CoV-2 variants. Some of these novel mAbs have a prolonged therapeutic action, while some are formulated as a combination of two or three mAbs to counteract the impact of evolving SARS-CoV-2 spike protein mutations.

• One of the investigational anti-spike mAbs is being evaluated using an alternative route of administration (by inhalation), while another is being explored for a novel therapeutic option for long COVID.

Declaration of interest

RR Razonable received grants from Gilead, Regeneron and Roche (funds to the institution; all projects have been completed). RR Razonable receives compensation for serving on the DSMB of Novartis and Endpoint Adjudication Committee of Allovir (both work have been completed). RR Razonable is a member of the Board of Directors of American Society of Transplantation. The authors have 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

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.