Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT Trial
Abstract Introduction The randomized, placebo-controlled, double-blind MOVe-OUT trial demonstrated molnupiravir (800 mg every 12 h for 5 days) as safe and effective for outpatient treatment of mild-to-moderate COVID-19, significantly reducing the risk of hospitalization/death in high-risk adults. At...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2023-11-01
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| Series: | Infectious Diseases and Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s40121-023-00891-1 |
| _version_ | 1797376870436569088 |
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| author | Julie M. Strizki Jay A. Grobler Nicholas Murgolo Arthur Fridman Matthew G. Johnson Jiejun Du Patricia Carmelitano Michelle L. Brown Amanda Paschke Carisa De Anda |
| author_facet | Julie M. Strizki Jay A. Grobler Nicholas Murgolo Arthur Fridman Matthew G. Johnson Jiejun Du Patricia Carmelitano Michelle L. Brown Amanda Paschke Carisa De Anda |
| author_sort | Julie M. Strizki |
| collection | DOAJ |
| description | Abstract Introduction The randomized, placebo-controlled, double-blind MOVe-OUT trial demonstrated molnupiravir (800 mg every 12 h for 5 days) as safe and effective for outpatient treatment of mild-to-moderate COVID-19, significantly reducing the risk of hospitalization/death in high-risk adults. At the time of that report, virologic assessments from the trial were partially incomplete as a result of their time-intensive nature. Here we present final results from all prespecified virology endpoints in MOVe-OUT based on the full trial dataset. Methods Nasopharyngeal swabs were collected at baseline (day 1, prior to first dose) and days 3, 5 (end-of-treatment visit), 10, 15, and 29. From these samples, change from baseline in SARS-CoV-2 RNA titers (determined by quantitative PCR), detection of infectious SARS-CoV-2 (by plaque assay), and SARS-CoV-2 viral error induction (determined by whole genome next-generation sequencing) were assessed as exploratory endpoints. Results Molnupiravir was associated with greater mean reductions from baseline in SARS-CoV-2 RNA than placebo (including 50% relative reduction at end-of-treatment) through day 10. Among participants with infectious virus detected at baseline (n = 96 molnupiravir, n = 97 placebo) and evaluable post-baseline samples, no molnupiravir-treated participant had infectious SARS-CoV-2 by day 3, whereas infectious virus was recovered from 21% of placebo-arm participants on day 3 and 2% at end-of-treatment. Consistent with molnupiravir’s mechanism of action, sequence analysis demonstrated that molnupiravir was associated with an increased number of low-frequency transition errors randomly distributed across the SARS-CoV-2 RNA genome compared with placebo (median 143.5 molnupiravir, 15 placebo), while transversion errors were infrequent overall (median 2 in both arms). Outcomes were consistent regardless of baseline SARS-CoV-2 clade, presence of SARS-CoV-2-specific immune response, or viral load. Conclusions A 5-day course of orally administered molnupiravir demonstrated a consistently greater virologic effect than placebo, including rapidly eliminating infectious SARS-CoV-2, in high-risk outpatients with mild-to-moderate COVID-19. Trial Registration ClinicalTrials.gov, NCT04575597. |
| first_indexed | 2024-03-08T19:45:49Z |
| format | Article |
| id | doaj.art-d0521e225c0440b48f259f56e15c4d93 |
| institution | Directory Open Access Journal |
| issn | 2193-8229 2193-6382 |
| language | English |
| last_indexed | 2024-03-08T19:45:49Z |
| publishDate | 2023-11-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Infectious Diseases and Therapy |
| spelling | doaj.art-d0521e225c0440b48f259f56e15c4d932023-12-24T12:25:08ZengAdis, Springer HealthcareInfectious Diseases and Therapy2193-82292193-63822023-11-0112122725274310.1007/s40121-023-00891-1Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT TrialJulie M. Strizki0Jay A. Grobler1Nicholas Murgolo2Arthur Fridman3Matthew G. Johnson4Jiejun Du5Patricia Carmelitano6Michelle L. Brown7Amanda Paschke8Carisa De Anda9Merck & Co., Inc.Merck & Co., Inc.Merck & Co., Inc.Merck & Co., Inc.Merck & Co., Inc.Merck & Co., Inc.Merck & Co., Inc.Merck & Co., Inc.Merck & Co., Inc.Merck & Co., Inc.Abstract Introduction The randomized, placebo-controlled, double-blind MOVe-OUT trial demonstrated molnupiravir (800 mg every 12 h for 5 days) as safe and effective for outpatient treatment of mild-to-moderate COVID-19, significantly reducing the risk of hospitalization/death in high-risk adults. At the time of that report, virologic assessments from the trial were partially incomplete as a result of their time-intensive nature. Here we present final results from all prespecified virology endpoints in MOVe-OUT based on the full trial dataset. Methods Nasopharyngeal swabs were collected at baseline (day 1, prior to first dose) and days 3, 5 (end-of-treatment visit), 10, 15, and 29. From these samples, change from baseline in SARS-CoV-2 RNA titers (determined by quantitative PCR), detection of infectious SARS-CoV-2 (by plaque assay), and SARS-CoV-2 viral error induction (determined by whole genome next-generation sequencing) were assessed as exploratory endpoints. Results Molnupiravir was associated with greater mean reductions from baseline in SARS-CoV-2 RNA than placebo (including 50% relative reduction at end-of-treatment) through day 10. Among participants with infectious virus detected at baseline (n = 96 molnupiravir, n = 97 placebo) and evaluable post-baseline samples, no molnupiravir-treated participant had infectious SARS-CoV-2 by day 3, whereas infectious virus was recovered from 21% of placebo-arm participants on day 3 and 2% at end-of-treatment. Consistent with molnupiravir’s mechanism of action, sequence analysis demonstrated that molnupiravir was associated with an increased number of low-frequency transition errors randomly distributed across the SARS-CoV-2 RNA genome compared with placebo (median 143.5 molnupiravir, 15 placebo), while transversion errors were infrequent overall (median 2 in both arms). Outcomes were consistent regardless of baseline SARS-CoV-2 clade, presence of SARS-CoV-2-specific immune response, or viral load. Conclusions A 5-day course of orally administered molnupiravir demonstrated a consistently greater virologic effect than placebo, including rapidly eliminating infectious SARS-CoV-2, in high-risk outpatients with mild-to-moderate COVID-19. Trial Registration ClinicalTrials.gov, NCT04575597.https://doi.org/10.1007/s40121-023-00891-1AntiviralCOVID-19DeltaInfectivityMK-4482Molnupiravir |
| spellingShingle | Julie M. Strizki Jay A. Grobler Nicholas Murgolo Arthur Fridman Matthew G. Johnson Jiejun Du Patricia Carmelitano Michelle L. Brown Amanda Paschke Carisa De Anda Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT Trial Infectious Diseases and Therapy Antiviral COVID-19 Delta Infectivity MK-4482 Molnupiravir |
| title | Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT Trial |
| title_full | Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT Trial |
| title_fullStr | Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT Trial |
| title_full_unstemmed | Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT Trial |
| title_short | Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT Trial |
| title_sort | virologic outcomes with molnupiravir in non hospitalized adult patients with covid 19 from the randomized placebo controlled move out trial |
| topic | Antiviral COVID-19 Delta Infectivity MK-4482 Molnupiravir |
| url | https://doi.org/10.1007/s40121-023-00891-1 |
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