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AGILE trial reports on antiviral activity of molnupiravir in vaccinated and unvaccinated individuals infected with contemporaneous variants of SARS-CoV-2

The antiviral drug molnupiravir received regulatory approval for treating people with mild to moderate COVID-19 who are at increased risk of developing severe disease in November 2021. These approvals were based solely on data from unvaccinated individuals which showed the drug was effective at reducing the risk of death and hospital admissions in those at highest risk of severe COVID-19. Uncertainty as to the effectiveness of molnupiravir in highly vaccinated populations is a limitation to its use today.

The latest results from the AGILE platform (published in The Lancet Infectious Diseases) reports evidence of antiviral activity (faster clearance of virus) with molnupiravir in a population of vaccinated and unvaccinated participants infected with a broad range of SARS-COV-2 viral variants. AGILE is a consortium comprising NIHR Clinical Research Facilities across the UK, the NIHR Southampton Clinical Trials Unit, Liverpool School of Tropical Medicine, and other partners and is led by the University of Liverpool.

“In a constantly changing pandemic, it is essential to understand if drugs remain effective in today’s population with the circulating variants we encounter” says Professor Saye Khoo, Chief Investigator for AGILE. “We observed an antiviral effect in both vaccinated and unvaccinated people, infected with variants including Delta and Omicron. What we do not yet know is how much of this antiviral benefit translates into clinical benefit – since risk of severe COVID-19 depends on factors such as the immune system, concomitant diseases and host characteristics”

The AGILE team initially undertook a Phase I trial of molnupiravir, evaluating a range of dosing in order to determine the optimal dose of molnupiravir for treating COVID-19. These data (published last year) were shared with the manufacturers Merck who subsequently undertook their pivotal late-phase licensing trial in unvaccinated patients. AGILE meanwhile continued with this phase II trial in the wider population of both vaccinated and unvaccinated patients, enrolling across the NIHR Clinical Research Facilities in Liverpool, Southampton, Manchester, Lancashire and London.

Professor Gareth Griffiths, Director of the Southampton Clinical Trials Unit, says: “The results from this trial do not contradict the existing evidence of a moderate benefit from molnupiravir. We have shared our trial findings with colleagues in Oxford who are coordinating the PANORAMIC trial, a much larger study in a highly vaccinated population, which will help add further evidence to the potential benefits of molnupiravir.”

Samples collected from participants in the AGILE trial are now being analysed in the laboratory to gain a better understanding of which patients and COVID-19 variants molnupiravir can be most effective for and in the hope it is a suitable a drug for everyone in the community to access as soon as they are found to have COVID-19.

Professor Griffiths continues: “Following on from these positive results, the AGILE platform is moving forward with its next trial to see whether a combination of two antivirals, molnupiravir and Paxlovid, can be even more effective in combatting the COVID-19 infection, and we expect to open to recruitment in Southampton and other CRFs later this month”.


Notes to Editors:

AGILE is an academic clinical trial platform led by the University of Liverpool and the NIHR Southampton Clinical Trial Unit, in partnership with researchers from the Liverpool Tropical School of Medicine and NIHR Liverpool and Broadgreen Clinical Research Facility. It has been established to enable the rapid clinical evaluation of potential COVID-19 therapeutics across the UK CRF Network. Visit the AGILE website.  

Project overview: