A further analysis of trial data suggests additional clinical benefits of molnupiravir in the treatment of patients infected with COVID-19
The clinical benefits of molnupiravir may not just be restricted to a reduction in either hospitalisation or death, according to the results of a secondary analysis of data from the MOVe-OUT trial by an international group of researchers in collaboration with the manufacturer, Merck and Co.
Molnupiravir is a small-molecule ribonucleoside prodrug of N-hydroxycytidine (NHC) and was studied in MOVe-OUT a phase 3, double-blind, randomised, placebo-controlled trial.
The aim of the trial was to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in non-hospitalised, unvaccinated adults with mild-to-moderate, COVID-19 and at least one risk factor for severe COVID-19 illness.
The findings of the study indicated that the drug, given at a dose of 800 mg every 12 hours for 5 days, was able to reduce the risk of hospitalisation or death when given within 5 days of the onset of COVID-19 symptoms.
While molnupiravir was clearly effective, researchers wondered if there were any further clinical benefits attributable to the drug and therefore decided to perform a secondary analysis of data generated in the trial. In particular, the researchers focused on the need for respiratory interventions, COVID-19-related acute care visits and changes in the level of inflammatory markers such as C-reactive protein (CRP). The reported outcomes were assessed in terms of the relative risk reduction (RRR).
Additional clinical benefits of molnupiravir
The trial randomised 1433 participants to either molnupiravir or placebo. A reduction in CRP levels was noted as early as day 3 and this was greater than for the placebo group (-1.44 vs 1.92, molnupiravir vs placebo, p value not stated) and in fact, CRP levels in the placebo group did not reduce until day 10.
Fewer patients given molnupiravir required any respiratory interventions (RRR = 34.3%, 95% CI 4.3% – 54.9%), in particular noninvasive mechanical ventilation (RRR = 75.4%). In addition, among the subgroup of patients who became hospitalised, fewer treated with molnupiravir required any form of respiratory intervention (RRR = 21.3%).
There was also difference in the proportion of molnupiravir patients requiring either an acute care visit (RRR = 32.1%) or a COVID-19-related acute care visit (RRR = 33.8%) compared to those taking placebo.
While there were apparent improvements in numerical changes in CRP values, the authors did not report the associated statistics for the change and it is therefore unclear whether the observed differences between the outcomes examined were statistically significant. It is also unclear if these differences were clinically meaningful.
A further limitation recognised by the authors was that the data were derived from patients who were unvaccinated against COVID-19 and so the generalisability of the findings to patients already vaccinated are not clear.
Despite these limitations, the authors concluded that their findings suggested added clinical benefits from the use of molnupiravir in the treatment of non-hospitalised adults with mild to moderate COVID-19.
Johnson MG et al. Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19. A Randomized, Placebo-Controlled Trial Ann Intern Med 2022