Molnupiravir speeds up recovery, reduces viral load of vaccinated COVID-19 patients

In vaccinated adults with COVID-19 who are at higher risk of adverse outcomes, treatment with molnupiravir in addition to usual care falls short of reducing the rates of hospitalizations and deaths, as shown by the results of the PANORAMIC study.

However, use of molnupiravir along with usual care has accelerated the recovery time of COVID-19 patients and has resulted in lower viral detection and load.

Findings from the PANORAMIC study were presented at the recent ECCMID 2023 in Copenhagen, Denmark, by Chris Butler, lead researcher and clinical director of the University of Oxford Primary Care and Vaccines Clinical Trial Collaborative in the UK.

“The safety, effectiveness, and cost-effectiveness of molnupiravir in patients in the community who are vaccinated has not been established,” according to the researchers, who then sought to establish whether molnupiravir added to usual care reduced hospital admissions/deaths among those at increased risk from COVID-19. [ECCMID 2023, abstract O1118]

Butler and his team identified patients aged ≥50, or ≥18 years with comorbidities, and unwell ≤5 days with confirmed COVID-19 in the community and enrolled them in this multicentre, open-label, adaptive, multi-arm, platform, randomized controlled trial.

They randomized a total of 25,708 eligible participants (mean age 56.6 years) between 8 December 2021 and 7 April 2022 to receive either molnupiravir 800 mg twice daily for 5 days plus usual care (n=12,744) or usual care alone (n=12,934). Nearly all patients (99 percent) had received at least a single dose of SARS-CoV-2 vaccine.

Using Bayesian models, the researchers then analysed all-cause hospitalization and death within 28 days, the primary outcome measure.

Of the participants, 25,054 (97 percent) had available data for the primary endpoint. One hundred five out of 12,529 (0.8 percent) hospitalizations or deaths were recorded in the molnupiravir group. This rate was similar to that in the usual care alone group (98/12,525; 0.8 percent), with a posterior probability of superiority of 0.33 (adjusted odds ratio, 1.06, 95 percent credible interval [CI], 0.81‒1.41).

The median time to first recovery (TTR) from randomization (the secondary outcome) was faster in the molnupiravir group than in the usual care group (9 vs 15 days). The estimated benefit in TTR was 4.2 days (95 percent CI, 3.8‒4.6), with a posterior probability of superiority of >0.999 (median TTR, 10.3 vs 14.5 days; hazard ratio, 1.36, 95 percent CI, 1.3‒1.4), meeting the prespecified superiority threshold.

In addition, SARS-CoV-2 on day 7 was below detection levels in seven out of 34 (21 percent) patients in the molnupiravir arm compared to one out of 39 (3 percent) in the usual care arm (p=0.039). Those who received molnupiravir showed a much lower mean viral load.

Notably, no significant between-group difference was noted in serious adverse events, which occurred in 50 (0.4 percent) participants in the molnupiravir group and 45 (0.4 percent) in the usual care group.

“Molnupiravir did not reduce already low hospitalizations [or] deaths among higher risk, vaccinated adults with COVID-19 in the community but resulted in faster time to recovery and reduced viral detection and load,” the researchers said.