December 16, 2021

expert reaction to results from trial investigating molnupiravir for oral treatment of Covid-19 in non-hospitalised patients

Trial results published in the New England Journal of Medicine (NEJM) look at the use of molnupiravir for oral treatment of COVID-19 in non-hospitalised patients.

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“This paper reports a well conducted and clearly reported randomised controlled trial of molnupiravir in patients who have not been vaccinated and have shown symptoms of infection with SARS-CoV-2 which has been confirmed by laboratory testing.  They were all given the treatment within five days of symptom onset and were regarded as being at high risk of going into hospital or dying.

“The trial had a planned interim analysis and that analysis showed good evidence of efficacy against hospitalisation or death.  This led the data-monitoring committee to recommend that the trial cease recruitment.  The UK MHRA authorised molnupiravir on the basis of these interim results.  It is not unusual, having stopped a trial early because of benefit or harm which may be an extreme result, to find that subsequent data, accrued when the follow-up of those in the trial when it was stopped has been completed, are less extreme so show less difference between the treatments being compared.  This seems to be what has happened in this trial so that the final results, while showing efficacy, are not as good as the interim results suggested.

“The overall evidence of efficacy may be reasonably clear, but it does seem likely that the interim results overestimated that efficacy.

“It must also be realised that the efficacy shown is notably less than that shown overall with the authorised vaccines.  At the same time, it may be the case that this treatment could be beneficial for those who for medical reasons cannot be vaccinated or in whom the response to vaccination is likely to be very limited.  We do not know why the participants were unvaccinated.  From the results shown to the US FDA, it was clear that most patients came from Latin America or Europe where the reasons may be various.  It should be noted that the results did not show evidence of benefit in those who had had a prior infection with SARS-CoV-2.

“While this could be a useful drug, it is not a panacea for where vaccination does not occur.  The trial was conducted in situations where the omicron variant was not circulating so results for that variant are inevitably speculative.”

‘Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients’ by A. Jayk Bernal et al. was published in the New England Journal of Medicine at 22:00 UK time on Thursday 16 December 2021.

DOI: 10.1056/NEJMoa2116044

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Stephen Evans: “No conflicts of interest.  I am funded (one day per week) by LSHTM.  They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator on any grants obtained from them.  I am the statistician to the ‘meta-Data Safety and Monitoring Board’ for CEPI.  I am paid for my attendance at those meetings and will be paid expenses for travel if that occurs.  I am a participant in the Oxford/Astra Zeneca trial, and on 13th January 2021 learnt I had received the active vaccine.”