Molnupiravir eliminates viral load, improves symptoms in patients with COVID-19

The investigational oral antiviral molnupiravir eliminated actively infectious SARS-CoV-2, improved self-reported outcomes and benefited immunocompromised patients with COVID-19, according to three separate analyses of the MOVe-OUT study.

The European Congress of Clinical Microbiology and Infectious Diseases released the data ahead of its meeting, which is being held later this month. The drug is one of two antivirals that are authorized for the treatment of COVID-19 in the United States. It was developed by Merck in collaboration with Ridgeback Biotherapeutics.

Previous data from the randomized, placebo-controlled, double-blind, multisite MOVe-OUT trial showed that molnupiravir reduced the risk for hospitalization or death among non-hospitalized adults with mild to moderate COVID-19 who were at risk for severe disease.

Viral load

In the first new analysis, Julie Strizki, PhD, a principal scientist at Merck, and colleagues analyzed data from 92 participants who were randomly assigned to receive a 5-day course of twice-daily molnupiravir (800 mg) and 96 participants who were randomly assigned to receive placebo. They reported that actively infectious SARS-CoV-2 was eliminated by day 3 in all participants who received molnupiravir compared with 21.8% of participants who received placebo. It took many participants in the placebo group up to 5 days or longer to achieve viral elimination, according to the researchers.

“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,” Strizki said in a press release. “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.”

Immunocompetence

In the second analysis, Matthew G. Johnson, MD, of Merck, and colleagues specifically evaluated immunocompromised participants in the MOVe-OUT trial, representing 4% of the original cohort. Among them, 25 participants received molnupiravir and 32 received placebo.

The researchers reported that participants in the treatment group were less likely to be hospitalized or die by day 29 (8% vs. 25%). Moreover, all immunocompromised patients who received molnupiravir had no evidence of infectious virus by day 3 compared with 14% of participants who received placebo.

There were no notable differences in virologic outcomes among immunocompromised and non-immunocompromised participants who were treated with molnupiravir, Jay Grobler, MD, the associate vice president of infectious diseases and vaccines at Merck, told Healio.

“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,” Johnson and colleagues wrote.

Symptom severity

In the third analysis, Yanfen Guan, MS, a principal scientist at Merck, and colleagues evaluated outcomes among 709 participants in the treatment group and 699 participants in the placebo group who had at least one COVID-19 symptom at the time of randomization. The participants were required to complete a 15-item daily symptom diary, in which they rated the severity of their symptoms from baseline to day 29. The researchers defined the time to sustained improvement as the time to the first of 3 consecutive days of reduced symptom severity without relapse. Time to progression was defined as the time to the first of two consecutive days of worsening symptom severity compared with baseline.

According to the researchers, participants who received molnupiravir were more likely to experience sustained improvements through day 29 and less likely to experience symptom progression compared with participants who received placebo. Guan and colleagues reported that the greatest observed benefit of the treatment occurred with loss of smell and fatigue. The proportion of participants who achieved sustained improvements by day 3, day 5 and day 10 were:

• 28.3%, 42.8% and 65.6% in the treatment group vs. 25%, 37.8% and 56.3% in the placebo group for shortness of breath or difficulty breathing;
• 19%, 32.4% and 51.7% in the treatment group vs. 17%, 29.1% and 53% in the placebo group for cough;
• 27.4%, 45,4% and 66.5% in the treatment group vs. 24.5%, 41.5% and 61% in the placebo group for fatigue;
• 14.8%, 29.7% and 53.2% in the treatment group vs. 11.5%, 23.1% and 47.5% in the placebo group for loss of smell; and
• 16.1%, 30.7% and 57.2% in the treatment group vs. 14.1% 26.9% and 51.9% in the placebo group for loss of taste.

“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-hospitalized patients with COVID-19 in the early stages of their symptoms,” Guan and colleagues wrote.

As of yet there is no clinical data on molnupiravir’s efficacy in individuals infected with BA.2 which is the predominant lineage of the omicron variant in the U.S., according to Grobler.

References:

Data from investigational COVID-19 antiviral drug molnupiravir suggest better outcomes for most COVID-related symptoms than placebo. https://www.eurekalert.org/news-releases/948344. Published March 31, 2022. Accessed April 1, 2022.

Guan Y, et al. Impact of molnupiravir treatment on patient-reported COVID-19 symptoms in the MOVe-OUT study. Presented at: European Congress of Clinical Microbiology and Infectious Diseases; April 23-26, 2022; Lisbon.

Johnson MG, et al. Molnupiravir for treatment of COVID-19 in immunocompromised patients: efficacy, safety, and virology results from the phase III MOVe-OUT trial. Presented at: European Congress of Clinical Microbiology and Infectious Diseases; April 23-26, 2022; Lisbon.

New analysis of investigational COVID antiviral drug molnupiravir shows it appears to clear virus equally well in immunocompromised patients and those who are immunocompetent. https://www.eurekalert.org/news-releases/948303. Published March 31, 2022. Accessed April 1, 2022.

New virology data shows the investigational COVID antiviral drug molnupiravir eliminates actively infectious SARS-CoV-2 virus by day 3 of starting therapy. https://www.eurekalert.org/news-releases/948301. Published March 31, 2022. Accessed April 1, 2022.

Strizki J, et al. Virologic outcomes from MOVe-OUT, a randomized, controlled phase III trial evaluating molnupiravir for treatment of COVID-19 in non-hospitalized adults. Presented at: European Congress of Clinical Microbiology and Infectious Diseases; April 23-26, 2022; Lisbon.