Safety, Tolerability, Pharmacokinetics, and Viral Pharmacodynamics of the Monoclonal Antibody Sotrovimab Administered via Intramuscular Injection in Participants with Early, Mild-to-Moderate COVID-19 - A Randomized Clinical Trial

Sep 28, 2026

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Objective and background focus on increasing access to COVID-19 therapeutics through intramuscular (IM) formulations. COMET-PEAK evaluates sotrovimab safety, tolerability, pharmacokinetics, and viral pharmacodynamics in adults with early, mild-to-moderate disease. Parts compare 500-mg IV infusion with 500-mg or 250-mg IM injection. Primary virologic equivalence uses mean SARS-CoV-2 viral load area under the curve day 1–8 and 90% CI criteria. Results show IM well tolerated and equivalent to 500-mg IV without new safety signals; viral load biomarker validity needs further study.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Introduction

Methods

Study Design and Endpoints

Drugs in R&D (2025) 25:353–365 [https://doi.org/10.1007/s40268-025-00529-2](https://doi.org/10.1007/s40268-025-00529-2) Safety, Tolerability, Pharmacokinetics, and Viral Pharmacodynamics of the Monoclonal Antibody Sotrovimab Administered via Intramuscular Injection in Participants with Early, Mild‑to‑Moderate COVID‑19: A Randomized Clinical Trial Anil Gupta1 · Maria Teresa Perez‑Rodríguez2 · Yaneicy Gonzalez‑Rojas3 · Moti Ramgopal4 · Almena Free5 · Jennifer Han6,13 · Jennifer Moore7 · Naomi Givens8 · Phillip J. Yates8 · Jill T. Walker6 · Mary Beth Connolly9 · Gretja Schnell10 · Varsha Imber7 · Rabia Anselm7 · Lindsay Winograd11 · Scott Segal6 · Stephen Harrison8 · Andrew Skingsley7 · Melissa Aldinger10 · Amanda Peppercorn6 · Jaynier Moya12 Received: 4 April 2025 / Accepted: 10 November 2025 / Published online: 24 November 2025 © The Author(s) 2025 Abstract Background and Objectives New coronavirus disease 2019 (COVID-19) therapeutics, including intramuscular (IM) formulations, may increase patient access. In COMET-TAIL, sotrovimab 500 mg IM was non-inferior to 500 mg intravenous (IV) in reducing the risk of COVID-19 progression; however, 250 mg IM was associated with more hospitalizations, despite similar viral load (VL) reductions to 500 mg IM. Methods COMET-PEAK was a randomized, three-part study to assess safety, tolerability, and viral pharmacodynamics of sotrovimab in adults with early, mild-to-moderate COVID-19. Parts B/C evaluated sotrovimab 500-mg IV infusion versus 500-mg or 250-mg IM injection. The primary objective was to compare virologic response of sotrovimab IM versus IV (mean area under the curve from day 1 to day 8 [AUCD1–8] of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] VL); 90% confidence interval (CI) limits of 0.5–2.0 indicated equivalence. Results Parts B/C included 167 and 157 participants, respectively. Median age range was 42–47 years, and approximately 50% of participants had one or more risk factor for severe disease. The primary objective was met: the ratio of geometric mean VL AUCD1–8 of sotrovimab IM versus IV was 1.04 (90% CI 0.98–1.09; Part B) and 1.02 (90% CI 0.94–1.11; Part C) . No new safety signals emerged for sotrovimab; IM administration was well tolerated, with few injection-site reactions. Conclusions Both sotrovimab IM doses were equivalent to 500 mg IV with respect to SARS-CoV-2 VL change. IM administration was safe and well tolerated. The validity of VL as a biomarker for COVID-19 progression warrants further study. Clinical Trial Registration NCT04779879 (date of first registration: March 3, 2021), [https://classic](https://classic).clinicaltrials.gov/ct2/ show/NCT04779879 . 1 Introduction Since the World Health Organization declared coronavirus disease 2019 (COVID-19) to be a global pandemic in March 2020, the COVID-19 landscape has continued to evolve, both in terms of viral variants and treatment options. There are multiple opportunities for therapeuticsto mitigate the burden of COVID-19 disease, including treatments that limit progression of disease in mild-tomoderate cases, reduce mortality and long-term morbidity in severe cases, and protect individuals from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection both before and after exposure. The COVID-19 pandemic also stimulated the development and authorization of several vaccines, although reported effectiveness has been variable, and uptake has been limited [1–4] . Sotrovimab is a dual-action engineered human IgG1κ monoclonal antibody (mAb) derived from the parental mAb S309, a potent neutralizing mAb directed against the receptor-binding domain of the spike protein of SARSCoV-2 [5–8]. In the pivotal COMET-ICE phase III clinical trial, a 500-mg intravenous (IV) infusion of sotrovimab resulted in a statistically significant 79% reduction in relative risk (0 . 21, 95% confidence interval [CI] 0.09–0. 50) compared with placebo of all-cause >24-h hospitalization or death

FAQs

What was the main purpose of COMET-PEAK in early, mild-to-moderate COVID-19?

To assess the safety, tolerability, pharmacokinetics, and viral pharmacodynamics of sotrovimab given by IV infusion or IM injection.

How did the study define success for the primary virologic objective?

Equivalence was assessed using the ratio of geometric mean SARS-CoV-2 viral load AUCD1–8 for IM versus IV, with 90% confidence interval limits of 0.5–2.0.

What did the results show about IM administration of sotrovimab compared with IV?

IM administration was well tolerated, showed no new safety signals, and the viral load changes were equivalent to 500 mg IV for both IM doses.

Sep 28, 2026

Uploaded by Callum