Tixagevimab/cilgavimab for prevention and treatment of COVID-19: a review

ABSTRACT

Introduction

There is a need to protect vulnerable individuals who do not respond to vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), particularly following the emergence of new variants. Tixagevimab/cilgavimab, the only monoclonal antibody combination authorized for pre-exposure prophylaxis of coronavirus disease 2019 (COVID-19), demonstrated efficacy in unvaccinated individuals in the PROVENT study.

Areas covered

This review focuses predominantly on real-world evidence examining the effectiveness and safety of tixagevimab/cilgavimab in populations who are immunocompromised and otherwise vulnerable. The ability of tixagevimab/cilgavimab to neutralize Omicron subvariants, the appropriate dosage in vulnerable populations, and the impact of prior vaccination on tixagevimab/cilgavimab effectiveness are also discussed.

Expert opinion

The tixagevimab/cilgavimab combination is important in providing protection in people who either cannot have a full vaccination or respond poorly to COVID-19 vaccines. Abundant clinical data have emerged to inform clinical use in adults in need, although some additional data–formal pediatric and adolescent studies, plus information on optimal doses required to protect against emerging variants, and the ideal interval between tixagevimab/cilgavimab dosing and vaccination–would be welcomed. Importantly, despite the current effectiveness of tixagevimab/cilgavimab, we must recognize the possibility that resistant SARS-CoV-2 variants could emerge in the future.

KEYWORDS:

• Cilgavimab
• COVID-19
• immunocompromised
• Omicron
• pre-exposure prophylaxis
• SARS-CoV-2
• tixagevimab
• treatment

Article highlights

• In vulnerable individuals, as in healthy populations, tixagevimab/cilgavimab dosing results in measurable titers of antibodies against the severe acute respiratory syndrome coronavirus-2 spike protein receptor-binding domain

• Tixagevimab/cilgavimab has reduced neutralizing capacity against the Omicron BA.1 subvariant, but evidence supports that activity against BA.2 is retained in populations who are immunocompromised

• Efficacy and safety of tixagevimab/cilgavimab 300 mg/300 mg as pre-exposure prophylaxis in individuals who are immunocompromised are demonstrated by real-world evidence studies, while the lower 150 mg/150 mg dose is potentially not consistently protective against the early Omicron lineages

• The combination of vaccination and tixagevimab/cilgavimab dosing should provide the greatest protection against breakthrough infections in individuals who are immunocompromised

• Although there are some unanswered questions regarding the longer-term use of tixagevimab/cilgavimab, in many settings there do not appear to be any significant obstacles to the initial rollout of preventative dosing to adults in need

Acknowledgments

Medical writing support was provided by Lorna Forse, PhD, and editorial support was provided by Jess Galbraith, BSc, all of Core Medica, London, UK, supported by AstraZeneca according to Good Publication Practice guidelines. AstraZeneca funded medical writing and article processing charges for this manuscript, and reviewed from a legal, IP, and technical perspective, but did not otherwise influence content of the article. Ultimate responsibility for opinions, conclusions, and data interpretation lies with the author, who was involved in the drafting and critical revision of the manuscript and approved the final version.

Declaration of interests

The author has conducted clinical trials for AstraZeneca, and reports honoraria/speaker fees from AstraZeneca, Sanofi, Merck, Janssen, GSK, and Gilead, and advisory boards for Gilead, Merck, and ViiV/GSK. 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 material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

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

Author contributions

The author has (1) designed the review article and interpretated the relevant literature, and (2) been involved in writing the review article and revising it for intellectual content.

Additional information

Funding

AstraZeneca funded medical writing and article processing charges for this manuscript. The author received no direct payment for the development of this article.