Media release

From: European Congress on Clinical Microbiology & Infectious Diseases (ECCMID)

New virology data shows the investigational COVID antiviral drug molnupiravir eliminates actively infectious SARS-CoV-2 virus by day 3 of starting therapy

New data to be presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022, Lisbon, 23-26 April) shows that participants taking the new anti-COVID drug molnupiravir eliminate actively infectious SARS-CoV-2 virus by day 3 of starting therapy, while many participants who received placebo took up to 5 days and in some cases longer to achieve this. The study is by Dr Julie Strizki and colleagues of the pharmaceutical company MSD, a trade name of Merck & Co., Inc, Kenilworth, NJ, USA, who manufacture molnupiravir (brand name Lagevrio).

Molnupiravir is an oral antiviral prodrug with broad activity against coronaviruses, including SARS-CoV-2 and its variants of concern. The randomised, placebo-controlled, double-blind phase 2/3 MOVe-OUT trial (already published in NEJM, see link below) confirmed superiority of molnupiravir over placebo in non-hospitalised adults with mild/moderate COVID-19 at risk of progression to severe disease, provided they started therapy within five days of symptom onset.  The drug has been granted an emergency use authorisation by the by the US Food and Drug Administration (FDA) and is also authorised for use in the UK, Australia, and Japan and 12 other jurisdictions.*

PCR testing was used to determine SARS-CoV-2 RNA viral loads from nasopharyngeal swabs collected on days 1 (baseline), 3, 5 (end-of-treatment visit), 10, 15, and 29.  This new study reports the final analyses of virologic outcomes from this trial. The analysis includes participants with infectious virus isolated at baseline and who had a post-baseline SARS-CoV-2 RNA sample available (n=92 molnupiravir, n=96 placebo).

Results demonstrated that on day 3 of treatment, infectious SARS-CoV-2 was detected in zero of 92 of participants with infectious virus at baseline who received molnupiravir, compared with 21.8% (20/96) of participants who received placebo. At Day 5, virus was detected in 0.0% (n=0/91) in the molnupiravir arm compared with 2.2% (n=2/89) in the placebo arm. At Day 10, no virus was detected in either arm for patients with infectious virus at baseline.

Dr Strizki concludes: “This analysis of the final virologic outcome data from MOVe-OUT confirms previous observations demonstrating that a 5-day treatment course of twice-daily 800 mg molnupiravir results in a more rapid decline in viral RNA and faster elimination of infectious virus than placebo... This study provides additional evidence that molnupiravir helps those infected clear SARS-CoV-2 faster than placebo, and supports MOVe-OUT’s primary finding that molnupiravir can lower the risk of progression to serious illness in this high-risk cohort.”

Molnupiravir is now in the process being submitted to global regulatory authorities for emergency use authorisation or approval in other countries and jurisdictions, such as the European Medicines Agency (EMA) and is being studied in a Phase 3 trial, MOVe-AHEAD, to evaluate it in a prophylaxis setting.

New analysis of investigational COVID antiviral drug molnupiravir shows it appears to clear virus equally well in immunocompromised patients and those who are immunocompetent

A new analysis of data on the ‘COVID-19 pill’ molnupiravir shows it appears to clear active SARS-CoV-2 virus equally well in immunocompromised patients and those who are immunocompetent. The analysis, which will be presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022, Lisbon, 23-26 April), was led by Dr Matthew Johnson, of the pharmaceutical company MSD, a trade name of Merck & Co., Inc, Kenilworth, NJ, USA, who manufacture molnupiravir (brand name Lagevrio)

Data on the efficacy of molnupiravir on cutting the risk of progression of COVID-19 in non-hospitalised, unvaccinated patients at the highest risk of poor outcomes (the MOVe-OUT study), was published in NEJM in December 2021*. All patients in the study were given the drug within 5 days of symptom onset. The drug has been granted an emergency use authorisation by the by the US Food and Drug Administration (FDA) and is also authorised for use in the UK, Australia, and Japan and 12 other jurisdictions.*

This new analysis of that study focuses on people categorised as immunosuppressed, meaning their immune systems do not function normally for a wide variety of reasons. Immunocompromised participants were identified based on prior/concomitant medication use and medical history, and included patients with active cancer (29), HIV (12), those using immunosuppressants (14), and transplant patients (5).

Among 1433 participants randomised in MOVe-OUT, 57 (4%) were identified as immunocompromised (see table 1 – 25 in the molnupiravir group, 32 in the placebo group). In the molnupiravir group, fewer immunocompromised participants were hospitalised or died by day 29 (2/25 [8%]) compared with placebo (8/32 [25%]).

Mean change from baseline in SARS-CoV-2 RNA was greater in the molnupiravir group versus placebo at day 3 in both the immunocompromised and non-immunocompromised participants (Table 2). No infectious virus was recovered in any immunocompromised participants in the molnupiravir group at Day 3 or later, versus 14% (4/29) with infectious virus at Day 3 with placebo (note for 3 of the 32 patients in the placebo group, a day 3 sample was not available – hence 29 instead of 32 participants in placebo group included here). The safety profile was comparable in the molnupiravir and placebo groups, regardless of immunocompromised status.

The authors say: “Immunocompromised participants receiving molnupiravir in the MOVe-OUT trial demonstrated a lower incidence of hospitalisation or death by day 29 compared to those receiving placebo, and molnupiravir was generally well tolerated. Reductions in the amount of SARS-CoV-2 virus over time were similar in immunocompromised and non-immunocompromised participants, and no infectious virus was detected after baseline in the molnupiravir group, suggesting that molnupiravir stops viral replication equally well in both the immunocompromised and immunocompetent patients in our trial population.”

The authors acknowledge that immunocompromised participants (4%) represented only a small proportion of the participants in this study, which was a was an exploratory post hoc analysis of the original MOVe-OUT study. They say no additional clinical studies focused on immunocompromised patients are planned at this time. The also add that while this final phase 3 study of the MOVe-OUT/molnupiravir recruited only unvaccinated participants, they believe a range of medicines and vaccines will be needed to confront the COVID-19 pandemic.

Data from investigational COVID-19 antiviral drug molnupiravir suggest better outcomes for most COVID-related symptoms than placebo

An analysis of patient-reported data on the investigational COVID-19 antiviral drug molnupiravir suggests better outcomes in patients with molnupiravir treatment compared to placebo for most COVID-related symptoms. The analysis, which will be presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022, Lisbon, 23-26 April), is led by Yanfen Guan, of the pharmaceutical company MSD, a trade name of Merck & Co., Inc, Kenilworth, NJ, USA, who manufacture molnupiravir (brand name Lagevrio).

Data on the efficacy of molnupiravir in reducing the risk of progression of COVID-19 in non-hospitalised, unvaccinated patients at the highest risk of poor outcomes (the MOVe-OUT study), was published in NEJM in December 2021*. All patients in phase 3 of the study were randomised and given molnupiravir or placebo within 5 days of symptom onset. The drug has been granted an emergency use authorisation by the by the US Food and Drug Administration (FDA) and is also authorised for use in the UK, Australia, and Japan and 12 other jurisdictions.*

To assess signs and symptoms directly from the patient’s perspective, this new analysis details self-reported symptoms evaluated as key secondary efficacy endpoints from the MOVe-OUT study.

Eligible participants were required to have at least one symptom attributable to COVID-19 at randomisation. Participants completed a 15-item daily symptom diary from Day 1 (randomisation) until Day 29, rating the severity of each symptom as: ‘none’, ‘mild’, ‘moderate’, or ‘severe’ (except loss of smell and loss of taste, rated as ‘yes’ or ‘no’).

For each symptom, time to sustained improvement/resolution was defined as the number of days from randomisation to the first of three consecutive days of reduced severity (without subsequent relapse by Day 29). Time to progression was defined as the number of days from randomisation to the first of two consecutive days of worsening severity, compared with baseline.

The ‘modified intention-to-treat’ analysis population (defined as randomised participants who received at least one dose of treatment and were not hospitalised prior to first dose) included 709 participants in the molnupiravir group and 699 in the placebo group. Diary completion rate was high: above 97% at Day 5 (end of treatment) and above 92% at Day 29 for any symptom in both treatment arms.

For most COVID-19 symptoms, sustained improvement/resolution was more likely in the molnupiravir than the placebo group through Day 29; the observed benefit was greatest for loss of smell and fatigue (see figure 1). Similarly, symptom progression was less likely with molnupiravir (see figure 2). When evaluating distinctive COVID-19 symptoms commonly associated with the disease including shortness of breath or difficulty breathing, cough, fatigue (tiredness), loss of smell, and loss of taste, participants in the molnupiravir group were more likely to achieve sustained improvement/resolution by Day 3, Day 5 (end of treatment), and Day 10 (figure 3).

The authors conclude: “In this study, we observed a positive impact of molnupiravir treatment on the outcome for most patient-reported COVID-19 symptoms compared to placebo, supporting the treatment benefits of molnupiravir for non-hospitaliaed patients with COVID-19 in the early stages of their symptoms.”