Medico-legal integration of molnupiravir rapid deployment during the COVID-19 pandemic: Emergency use authorization, clinical evidence, and risk of viral mutagenesis
- 1Graduate Institute of Law and Interdisciplinary Studies, College of Law, National Chengchi University, Taipei 116, Taiwan
Abstract
As one of the first oral antivirals authorized for outpatient treatment of COVID-19, molnupiravir (Lagevrio) illustrates the complex interplay among emergency regulatory frameworks, clinical trial evidence, and real-world outcomes. This narrative review synthesizes evidence from pivotal trials (MOVe-OUT, PANORAMIC), global genomic surveillance datasets, regulatory filings, and pharmacokinetic barrier studies to examine how eight interlocking U.S. statutory and administrative instruments compressed development timelines while sustaining product availability. Molnupiravir induces lethal mutagenesis in SARS-CoV-2; the FDA granted Emergency Use Authorization (EUA) in December 2021 based on interim data showing approximately a 50% reduction in hospitalization or death. Final trial analyses lowered this estimate to roughly 30%, and the large-scale PANORAMIC trial found no reduction in hospitalization or mortality among highly vaccinated populations. Emerging safety concerns-including teratogenicity, juvenile skeletal toxicity, and a molnupiravir-associated mutational signature detected across global viral genomic databases-further eroded its benefit-risk profile, contributing to the European Medicines Agency's 2023 refusal of marketing authorization and to the drug's lack of full FDA approval. Existing statutory frameworks nonetheless preserve molnupiravir's EUA status as a second-line option for high-risk patients. Its trajectory highlights the tension between emergency speed and long-term pharmacovigilance and offers actionable, One Health-informed lessons for pandemic-preparedness legislation.
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BibTeX
@article{tsai2026medicolegal,
title = {{Medico-legal integration of molnupiravir rapid deployment during the COVID-19 pandemic: Emergency use authorization, clinical evidence, and risk of viral mutagenesis}},
author = {Tung-Hu Tsai},
journal = {One health (Amsterdam, Netherlands)},
year = {2026},
month = oct,
doi = {10.1016/j.onehlt.2026.101621},
url = {https://europepmc.org/article/PMC/PMC13716954},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Medico-legal integration of molnupiravir rapid deployment during the COVID-19 pandemic: Emergency use authorization, clinical evidence, and risk of viral mutagenesis
AU - Tung-Hu Tsai
PY - 2026
DA - 2026/10/17
JO - One health (Amsterdam, Netherlands)
DO - 10.1016/j.onehlt.2026.101621
UR - https://europepmc.org/article/PMC/PMC13716954
AB - As one of the first oral antivirals authorized for outpatient treatment of COVID-19, molnupiravir (Lagevrio) illustrates the complex interplay among emergency regulatory frameworks, clinical trial evidence, and real-world outcomes. This narrative review synthesizes evidence from pivotal trials (MOVe-OUT, PANORAMIC), global genomic surveillance datasets, regulatory filings, and pharmacokinetic barrier studies to examine how eight interlocking U.S. statutory and administrative instruments compressed development timelines while sustaining product availability. Molnupiravir induces lethal mutagenesis in SARS-CoV-2; the FDA granted Emergency Use Authorization (EUA) in December 2021 based on interim data showing approximately a 50% reduction in hospitalization or death. Final trial analyses lowered this estimate to roughly 30%, and the large-scale PANORAMIC trial found no reduction in hospitalization or mortality among highly vaccinated populations. Emerging safety concerns-including teratogenicity, juvenile skeletal toxicity, and a molnupiravir-associated mutational signature detected across global viral genomic databases-further eroded its benefit-risk profile, contributing to the European Medicines Agency's 2023 refusal of marketing authorization and to the drug's lack of full FDA approval. Existing statutory frameworks nonetheless preserve molnupiravir's EUA status as a second-line option for high-risk patients. Its trajectory highlights the tension between emergency speed and long-term pharmacovigilance and offers actionable, One Health-informed lessons for pandemic-preparedness legislation.
SN - 2352-7714
ER -